Latest Drugwonks' Blog
Per Ed Silverman over at Pharmalot:
Seeking a way to alleviate high drug prices, a Utah lawmaker hopes to introduce a bill that would allow the state to import prescription medicines from Canada, a move that is likely to accelerate a fierce debate over drug costs and patient safety.
Over the next several weeks, Rep. Norman Thurston, a Republican, plans to submit legislation to authorize state officials to designate an existing pharmaceutical wholesaler to purchase prescription drugs from a wholesaler in Canada. His hope is that retail pharmacies based in Utah would then be able to buy and sell medicines at lower prices.
“We’re still trying to work out some of the details, but we envision a safe supply chain that would result in significant cost savings for the citizens of Utah,” he told us. To allay safety concerns, he envisions the bill would require prescription medicines to be approved by regulators in both Canada and the U.S.
“And the bill would establish a chain of custody just like we have for U.S. distribution,” he said. “It shouldn’t be a significant cost to the state to set up a program, fill out paperwork and get approval (from the U.S. Human and Health Services secretary). According to federal law, that’s the only approval we need.”
Even so, the move is likely to receive considerable pushback.
In general, importation sparks debate that Americans could be exposed to counterfeit medicines.
Last year, four former Food and Drug Administration commissioners penned an open letter arguing against importation, citing such concerns. And the pharmaceutical industry has regularly lobbied against any and all efforts to allow importation. Over the years, Congress has failed to pass various bills that were proposed. And more than a decade ago, several states pursued web sites to allow residents to purchase medicines from Canada, but those efforts eventually sputtered, as well.
“Good luck with this. No HHS Secretary of either party has ever declared that importation is safe,” said Peter Pitts, a former FDA associate commissioner who heads the Center for Medicine in the Public Interest, a think tank that is funded, in part, by the pharmaceutical industry.
“We have a closed regulatory system. Health Canada may be world class, but it doesn’t mean we can have multiple standards for drug approvals. What matters is how a drug is manufactured, stored, and dispensed. It sounds easy, but is extraordinarily hard.”
For his part, Thurston is doggedly optimistic.
In this instance (as it generally is with schemes to advance importation, “doggedly optimistic” = “deaf and dumb to reality.”
Let’s cut right to the chase. Generic drugs (85% + of all medicines volume in the US are LESS expensive than in Canada or any European country. Next, for the overwhelming number of Americans with private health insurance, the co-pays for their products are LESS expensive then buying them retail at either a brick-and-mortar of Internet Canadian pharmacy. Biologics? 85% of all biologics are administered in hospitals. Is Senator Sanders suggesting that American hospitals should import drugs that may or may not have been shipped under proper refrigeration conditions? FDA inspections speak otherwise.
The on-the-ground reality of state and local importation schemes has been dismal and politically embarrassing. Remember Illinois’ high profile “I-Save-RX” program? Over 19 months, only 3,689 Illinois residents used the program—that’s .02 percent of the population.
And what of Minnesota’s RxConnect? According to its latest statistics, Minnesota RxConnect fills about 138 prescriptions a month. That’s in a state with a population of 5,167,101.
Remember Springfield, Massachusetts and “the New Boston Tea Party?” Well, the city of Springfield has been out of the “drugs from Canada business” since August 2006.
And speaking of tea parties, according to a story in the Boston Globe, “Four years after Mayor Thomas M. Menino bucked federal regulators and made Boston the biggest city in the nation to offer low-cost Canadian prescription drugs to employees and retirees, the program has fizzled, never having attracted more than a few dozen participants.”
The Canadian supplier for the program was Winnipeg-based Total Care Pharmacy. When Total Care decided to end its relationship with the city, only 16 Boston retirees were still participating.
Programs like this wouldn’t do any better on a national basis. A study by the non-partisan federal Congressional Budget Office showed that importation would reduce our nation’s spending on prescription medicines a whopping 0.1 percent—and that’s not including the tens of millions of dollars the FDA would need to oversee drug safety for the dozen or so nations generally involved in foreign drug importation schemes.
In addition to importing foreign price controls, Americans would end up jeopardizing their health by purchasing unsafe drugs while not saving money.
A better policy for our new President and Congress to focus on is the issue of increasing insurance company co-pays and co-insurance. Dropping drug co-pays would also help patients stick to their prescribed treatment regimes. All too often, people skip a dose, don’t get a refill, or stop taking their drugs prematurely in order to save money. In the long run, though, not adhering to a drug regimen leaves patients less healthy — and increases national medical expenses by an estimated $300 billion annually.
When consumers say, “My drugs are too expensive,” what they mean is that their co-pays and co-insurance are too expensive. And they’re right. Major insurance companies and pharmacy benefit managers (PBM) receive significant discounts from the manufacturers. So why doesn’t this result in lower co-pays for consumers? That’s a good issue for our new political leadership to debate – both in Salt Lake City and Washington, DC.
Seeking a way to alleviate high drug prices, a Utah lawmaker hopes to introduce a bill that would allow the state to import prescription medicines from Canada, a move that is likely to accelerate a fierce debate over drug costs and patient safety.
Over the next several weeks, Rep. Norman Thurston, a Republican, plans to submit legislation to authorize state officials to designate an existing pharmaceutical wholesaler to purchase prescription drugs from a wholesaler in Canada. His hope is that retail pharmacies based in Utah would then be able to buy and sell medicines at lower prices.
“We’re still trying to work out some of the details, but we envision a safe supply chain that would result in significant cost savings for the citizens of Utah,” he told us. To allay safety concerns, he envisions the bill would require prescription medicines to be approved by regulators in both Canada and the U.S.
“And the bill would establish a chain of custody just like we have for U.S. distribution,” he said. “It shouldn’t be a significant cost to the state to set up a program, fill out paperwork and get approval (from the U.S. Human and Health Services secretary). According to federal law, that’s the only approval we need.”
Even so, the move is likely to receive considerable pushback.
In general, importation sparks debate that Americans could be exposed to counterfeit medicines.
Last year, four former Food and Drug Administration commissioners penned an open letter arguing against importation, citing such concerns. And the pharmaceutical industry has regularly lobbied against any and all efforts to allow importation. Over the years, Congress has failed to pass various bills that were proposed. And more than a decade ago, several states pursued web sites to allow residents to purchase medicines from Canada, but those efforts eventually sputtered, as well.
“Good luck with this. No HHS Secretary of either party has ever declared that importation is safe,” said Peter Pitts, a former FDA associate commissioner who heads the Center for Medicine in the Public Interest, a think tank that is funded, in part, by the pharmaceutical industry.
“We have a closed regulatory system. Health Canada may be world class, but it doesn’t mean we can have multiple standards for drug approvals. What matters is how a drug is manufactured, stored, and dispensed. It sounds easy, but is extraordinarily hard.”
For his part, Thurston is doggedly optimistic.
In this instance (as it generally is with schemes to advance importation, “doggedly optimistic” = “deaf and dumb to reality.”
Let’s cut right to the chase. Generic drugs (85% + of all medicines volume in the US are LESS expensive than in Canada or any European country. Next, for the overwhelming number of Americans with private health insurance, the co-pays for their products are LESS expensive then buying them retail at either a brick-and-mortar of Internet Canadian pharmacy. Biologics? 85% of all biologics are administered in hospitals. Is Senator Sanders suggesting that American hospitals should import drugs that may or may not have been shipped under proper refrigeration conditions? FDA inspections speak otherwise.
The on-the-ground reality of state and local importation schemes has been dismal and politically embarrassing. Remember Illinois’ high profile “I-Save-RX” program? Over 19 months, only 3,689 Illinois residents used the program—that’s .02 percent of the population.
And what of Minnesota’s RxConnect? According to its latest statistics, Minnesota RxConnect fills about 138 prescriptions a month. That’s in a state with a population of 5,167,101.
Remember Springfield, Massachusetts and “the New Boston Tea Party?” Well, the city of Springfield has been out of the “drugs from Canada business” since August 2006.
And speaking of tea parties, according to a story in the Boston Globe, “Four years after Mayor Thomas M. Menino bucked federal regulators and made Boston the biggest city in the nation to offer low-cost Canadian prescription drugs to employees and retirees, the program has fizzled, never having attracted more than a few dozen participants.”
The Canadian supplier for the program was Winnipeg-based Total Care Pharmacy. When Total Care decided to end its relationship with the city, only 16 Boston retirees were still participating.
Programs like this wouldn’t do any better on a national basis. A study by the non-partisan federal Congressional Budget Office showed that importation would reduce our nation’s spending on prescription medicines a whopping 0.1 percent—and that’s not including the tens of millions of dollars the FDA would need to oversee drug safety for the dozen or so nations generally involved in foreign drug importation schemes.
In addition to importing foreign price controls, Americans would end up jeopardizing their health by purchasing unsafe drugs while not saving money.
A better policy for our new President and Congress to focus on is the issue of increasing insurance company co-pays and co-insurance. Dropping drug co-pays would also help patients stick to their prescribed treatment regimes. All too often, people skip a dose, don’t get a refill, or stop taking their drugs prematurely in order to save money. In the long run, though, not adhering to a drug regimen leaves patients less healthy — and increases national medical expenses by an estimated $300 billion annually.
When consumers say, “My drugs are too expensive,” what they mean is that their co-pays and co-insurance are too expensive. And they’re right. Major insurance companies and pharmacy benefit managers (PBM) receive significant discounts from the manufacturers. So why doesn’t this result in lower co-pays for consumers? That’s a good issue for our new political leadership to debate – both in Salt Lake City and Washington, DC.
Biosimilarity? No one said it was going to be easy.
A smart and timely cross-post from RAPS ...
Sandoz Raises Questions With FDA Draft Guidance on Statistical Approaches for Biosimilars
Martin Schiestl, chief science officer at Novartis' Sandoz, on Tuesday explained how the US Food and Drug Administration's (FDA) draft guidance on statistical approaches to evaluate analytical similarity poses risks that could end up causing true biosimilars to be rejected randomly.
Schiestl told attendees of DIA's biosimilars conference in Bethesda, MD, that the problem is related to equivalence testing, which FDA says in the draft, "is typically recommended for quality attributes with the highest risk ranking and should generally include assay(s) that evaluate clinically relevant mechanism(s) of action of the product for each indication for which approval is sought."
The draft, released about a month ago, also notes: "Determining an appropriate margin is a critical but challenging step for equivalence testing in any setting. Ideally, it would be possible to establish and pre-specify a biologically or clinically meaningful equivalence margin based on scientific knowledge or past experience. Often, however, such a margin is not readily available for every quality attribute deemed important enough for Tier 1 testing in a biosimilar development program. With this limitation, FDA currently recommends use of an equivalence margin that is a function of the reference product's variability for the attribute being tested."
But Schiestl noted that monitoring the mean is useful in process development and post approval process monitoring.
However, for lot release decisions, "Compliance with a preset mean is an impossible criteria."
He added, "Strict adherence to equivalence testing for Tier 1 attributes makes biosimilar development a gamble. Justifications which may overrule a failed equivalence test should be added in the guidance."
Such justifications may include a scientific understanding of a variation and an "inconsistent mean of the reference product which might be caused by inherent process fluctuations within acceptable ranges, manufacturing changes or movements within a design space," Schiestl added.
A smart and timely cross-post from RAPS ...
Sandoz Raises Questions With FDA Draft Guidance on Statistical Approaches for Biosimilars
Martin Schiestl, chief science officer at Novartis' Sandoz, on Tuesday explained how the US Food and Drug Administration's (FDA) draft guidance on statistical approaches to evaluate analytical similarity poses risks that could end up causing true biosimilars to be rejected randomly.
Schiestl told attendees of DIA's biosimilars conference in Bethesda, MD, that the problem is related to equivalence testing, which FDA says in the draft, "is typically recommended for quality attributes with the highest risk ranking and should generally include assay(s) that evaluate clinically relevant mechanism(s) of action of the product for each indication for which approval is sought."
The draft, released about a month ago, also notes: "Determining an appropriate margin is a critical but challenging step for equivalence testing in any setting. Ideally, it would be possible to establish and pre-specify a biologically or clinically meaningful equivalence margin based on scientific knowledge or past experience. Often, however, such a margin is not readily available for every quality attribute deemed important enough for Tier 1 testing in a biosimilar development program. With this limitation, FDA currently recommends use of an equivalence margin that is a function of the reference product's variability for the attribute being tested."
But Schiestl noted that monitoring the mean is useful in process development and post approval process monitoring.
However, for lot release decisions, "Compliance with a preset mean is an impossible criteria."
He added, "Strict adherence to equivalence testing for Tier 1 attributes makes biosimilar development a gamble. Justifications which may overrule a failed equivalence test should be added in the guidance."
Such justifications may include a scientific understanding of a variation and an "inconsistent mean of the reference product which might be caused by inherent process fluctuations within acceptable ranges, manufacturing changes or movements within a design space," Schiestl added.
Last week’s commentary on Cigna’s plan to replace Oxycontin ER with Xtampza ER on its core formulary (Is Cigna Trading Patient Choice for Hidden Profits?) resulted in a very open and honest chat with a senior Cigna executive. He assured me that patient co-pays wouldn’t go up for Xtampza ER and that if a patient stays on Oxycontin after prior authorization, that the co-pay would also stay the same. So, good news for patients there.
I asked how this change in tiering would “guard against opioid abuse” (since both products are formulated with properties designed to deter intranasal – snorting, and intravenous -- injection abuse, and one isn't "better" than the other). The answer was that, because of the value-based contract, Collegium would be rewarded for “appropriate prescribing.” But since Collegium (the manufacturer of Xtampza ER) doesn’t prescribe (they sell) would their role be in detailing “best practices?” The executive didn’t know -- but promised to get get back to me with an answer. So, watch this space for more details.
I also mentioned to him that Purdue Pharma (as far as I know) is the only company actively detailing the CDC Opioid prescribing guidelines. The CDC guidelines seem to be a baseline requirement for enhanced physician education, and who better to do this than the manufacturers who are detailing directly to them? While the process in the development of the guidelines was not as transparent as they could have been, the guidelines themselves are a sensible foundation. Hopefully Cigna’s deal with Collegium will drive better prescriber awareness.
I asked how this change in tiering would “guard against opioid abuse” (since both products are formulated with properties designed to deter intranasal – snorting, and intravenous -- injection abuse, and one isn't "better" than the other). The answer was that, because of the value-based contract, Collegium would be rewarded for “appropriate prescribing.” But since Collegium (the manufacturer of Xtampza ER) doesn’t prescribe (they sell) would their role be in detailing “best practices?” The executive didn’t know -- but promised to get get back to me with an answer. So, watch this space for more details.
I also mentioned to him that Purdue Pharma (as far as I know) is the only company actively detailing the CDC Opioid prescribing guidelines. The CDC guidelines seem to be a baseline requirement for enhanced physician education, and who better to do this than the manufacturers who are detailing directly to them? While the process in the development of the guidelines was not as transparent as they could have been, the guidelines themselves are a sensible foundation. Hopefully Cigna’s deal with Collegium will drive better prescriber awareness.
From STAT News …
Why do we need drug rebates, anyway? A top lawmaker wants to know
WASHINGTON — Sen. Lamar Alexander has a question: why do we have drug rebates, anyway?
“Why do we need rebates?” the Tennessee Republican asked a panel of pharmaceutical industry representatives at a Senate committee hearing. The Health, Education, Labor, and Pensions committee met Tuesday morning for the second of three hearings on drug pricing, and heard testimony from five interest groups representing companies that play different roles in getting medicines to patients.
Rebates are payments made by drug manufacturers to “pharmacy benefit managers,” middlemen that negotiate drug prices on behalf of companies, unions, and government agencies. PBMs come up with lists of drugs that receive preferred coverage from insurers and also arrange rebates from drug makers in exchange for favorable insurance coverage.
Sometimes the payments that drug manufacturers make to PBMs are passed on to insurers, and sometimes insurers pass on to patients the savings from those rebates. But the amount of those payments are kept secret.
Sound complicated and opaque? Alexander seems to thinks so too.
“Why don’t we just get rid of rebates and let you negotiate directly with manufactures, take that $100 billion a year, and just reduce the list price?” Alexander asked Mark Merritt, president and chief executive officer of the Pharmaceutical Care Management Association, which represents pharmacy benefit managers. “Wouldn’t it be simpler for us to understand where the money goes?”
Alexander’s question seemed to betray a misunderstanding of the situation — as he admitted, “I have yet to figure out where [the money] goes” — because pharmacy benefit managers do negotiate directly with manufacturers to determine the rebate amount.
Merritt didn’t say yes or no, but classified rebates as basically “volume discounts,” enabling groups that purchase more drugs to get lower prices.
After the hearing, Merritt clarified to STAT that he would be open to axing rebates.
“We’d be happy if manufacturers would just go to lowering the actual price as opposed to rebating different suppliers and so forth,” Merritt said. “But I don’t see that happening anytime soon.”
Why do we need drug rebates, anyway? A top lawmaker wants to know
WASHINGTON — Sen. Lamar Alexander has a question: why do we have drug rebates, anyway?
“Why do we need rebates?” the Tennessee Republican asked a panel of pharmaceutical industry representatives at a Senate committee hearing. The Health, Education, Labor, and Pensions committee met Tuesday morning for the second of three hearings on drug pricing, and heard testimony from five interest groups representing companies that play different roles in getting medicines to patients.
Rebates are payments made by drug manufacturers to “pharmacy benefit managers,” middlemen that negotiate drug prices on behalf of companies, unions, and government agencies. PBMs come up with lists of drugs that receive preferred coverage from insurers and also arrange rebates from drug makers in exchange for favorable insurance coverage.
Sometimes the payments that drug manufacturers make to PBMs are passed on to insurers, and sometimes insurers pass on to patients the savings from those rebates. But the amount of those payments are kept secret.
Sound complicated and opaque? Alexander seems to thinks so too.
“Why don’t we just get rid of rebates and let you negotiate directly with manufactures, take that $100 billion a year, and just reduce the list price?” Alexander asked Mark Merritt, president and chief executive officer of the Pharmaceutical Care Management Association, which represents pharmacy benefit managers. “Wouldn’t it be simpler for us to understand where the money goes?”
Alexander’s question seemed to betray a misunderstanding of the situation — as he admitted, “I have yet to figure out where [the money] goes” — because pharmacy benefit managers do negotiate directly with manufacturers to determine the rebate amount.
Merritt didn’t say yes or no, but classified rebates as basically “volume discounts,” enabling groups that purchase more drugs to get lower prices.
After the hearing, Merritt clarified to STAT that he would be open to axing rebates.
“We’d be happy if manufacturers would just go to lowering the actual price as opposed to rebating different suppliers and so forth,” Merritt said. “But I don’t see that happening anytime soon.”
And there are just as many reasons to say "yes" to HHS.
WHY GOTTLIEB SHOULD STAY AT FDA
BY STEVE USDIN, WASHINGTON EDITOR, BIOCENTURY
Reports that FDA Commissioner Scott Gottlieb tops President Donald Trump’s list for replacing ousted HHS Secretary Tom Price are reverberating around the Washington echo chamber. The speculation has made its way into so many articles, blogs, tweets and cellphone conversations overheard on the Red Line Metro cars frequented by lobbyists, lawyers and journalists that it has acquired a patina of credibility, even inevitability.
I don’t claim to know whether the job will be offered to Gottlieb or if he would accept it. I do think the interests of patients, FDA, regulated industry and, most likely, Gottlieb himself would be best served if he remains at FDA. Here are four reasons why:
1. FDA NEEDS A STRONG PERMANENT L EADER
FDA needs stable leadership to produce the regulatory innovation that can turn today’s scientific advances into tomorrow’s medicines.
While the agency can maintain critical functions on autopilot, only a congressionally confirmed leader can break new ground or take controversial steps. Gottlieb has started to take FDA in new directions, for example by making public health arguments for lowering drug prices by tackling pharma company “gamesmanship,” and for making cigarettes less addictive. He has announced plans to release a plan for advancing biomedical innovation that will go beyond the requirements in the recently enacted 21st Century Cures Act and FDA Reauthorization Act.
These projects reflect Gottlieb’s personal experience and vision. It will take years to get them started and on a firm footing. They would likely wither if he departed.
2. FDA NEEDS A COMPETENT LEADER
While there certainly are other individuals with the necessary experience and competence to lead FDA, there is no reason to believe they would be nominated if Gottlieb departed.
When Gottlieb was nominated, serious contenders for the position included individuals who want to discard the standards and principles that have made FDA the gold standard for medical product regulation. These guys are still out there, tanned, rested and ready for their opportunity to dismantle the regulatory state and make the world safe for purveyors of snake oil.
3. GOTTLIEB’S NOT RIGH T FOR HHS
Gottlieb lacks the kind of experience required to successfully manage an organization with a trillion-dollar budget and 80,000 employees.
Someone who has been a state governor or headed a state health department or possibly a large university system would be better qualified to deal with the massive budgets, to manage government departments with diverse missions and to placate members of Congress with competing interests.
4. HEADING HHS IS A THANKLESS TASK
The person who steps into Price’s shoes will be pinned between a mercurial president prone to humiliating cabinet secretaries, and feuding Republican factions in Congress that are promoting incompatible and impossible healthcare agendas.
The next HHS secretary will be castigated by Republicans for failing to strangle the Affordable Care Act and vilified by Democrats for failing to shore it up. The secretary also will have to defend the Trump administration’s proposals to slash funding for public health and biomedical research. It is difficult to imagine anyone coming out of the job with their integrity and self-respect intact.
If he departs now, Gottlieb will leave no mark behind at FDA, and there aren’t great prospects for advancing the public good at HHS. In contrast, based on his current trajectory, if he stays on the job, Gottlieb is on track to leave with a strong, positive legacy.
WHY GOTTLIEB SHOULD STAY AT FDA
BY STEVE USDIN, WASHINGTON EDITOR, BIOCENTURY
Reports that FDA Commissioner Scott Gottlieb tops President Donald Trump’s list for replacing ousted HHS Secretary Tom Price are reverberating around the Washington echo chamber. The speculation has made its way into so many articles, blogs, tweets and cellphone conversations overheard on the Red Line Metro cars frequented by lobbyists, lawyers and journalists that it has acquired a patina of credibility, even inevitability.
I don’t claim to know whether the job will be offered to Gottlieb or if he would accept it. I do think the interests of patients, FDA, regulated industry and, most likely, Gottlieb himself would be best served if he remains at FDA. Here are four reasons why:
1. FDA NEEDS A STRONG PERMANENT L EADER
FDA needs stable leadership to produce the regulatory innovation that can turn today’s scientific advances into tomorrow’s medicines.
While the agency can maintain critical functions on autopilot, only a congressionally confirmed leader can break new ground or take controversial steps. Gottlieb has started to take FDA in new directions, for example by making public health arguments for lowering drug prices by tackling pharma company “gamesmanship,” and for making cigarettes less addictive. He has announced plans to release a plan for advancing biomedical innovation that will go beyond the requirements in the recently enacted 21st Century Cures Act and FDA Reauthorization Act.
These projects reflect Gottlieb’s personal experience and vision. It will take years to get them started and on a firm footing. They would likely wither if he departed.
2. FDA NEEDS A COMPETENT LEADER
While there certainly are other individuals with the necessary experience and competence to lead FDA, there is no reason to believe they would be nominated if Gottlieb departed.
When Gottlieb was nominated, serious contenders for the position included individuals who want to discard the standards and principles that have made FDA the gold standard for medical product regulation. These guys are still out there, tanned, rested and ready for their opportunity to dismantle the regulatory state and make the world safe for purveyors of snake oil.
3. GOTTLIEB’S NOT RIGH T FOR HHS
Gottlieb lacks the kind of experience required to successfully manage an organization with a trillion-dollar budget and 80,000 employees.
Someone who has been a state governor or headed a state health department or possibly a large university system would be better qualified to deal with the massive budgets, to manage government departments with diverse missions and to placate members of Congress with competing interests.
4. HEADING HHS IS A THANKLESS TASK
The person who steps into Price’s shoes will be pinned between a mercurial president prone to humiliating cabinet secretaries, and feuding Republican factions in Congress that are promoting incompatible and impossible healthcare agendas.
The next HHS secretary will be castigated by Republicans for failing to strangle the Affordable Care Act and vilified by Democrats for failing to shore it up. The secretary also will have to defend the Trump administration’s proposals to slash funding for public health and biomedical research. It is difficult to imagine anyone coming out of the job with their integrity and self-respect intact.
If he departs now, Gottlieb will leave no mark behind at FDA, and there aren’t great prospects for advancing the public good at HHS. In contrast, based on his current trajectory, if he stays on the job, Gottlieb is on track to leave with a strong, positive legacy.
From the pages of the Wall Street Journal …
A Flawed Study Depicts Drug Companies as Profiteers
Peter J. Pitts
Even the authors admit their selection criteria are a ‘critical limitation.’ That’s an understatement.
Are drug companies ripping off cancer patients? Of course they are, suggests a much-hyped study published last month in the journal JAMA Internal Medicine. The truth is more complicated.
Drug companies receive a staggering return on investment “not seen in other sectors of the economy,” write Vinay Prasad of Oregon Health and Science University and Sham Mailankody of Memorial Sloan Kettering Cancer Center. They estimate that pharmaceutical firms spend $720 million on average to develop a single cancer drug, while the average cancer therapy generates sales of $6.7 billion.
The editors at JAMA are brilliant physicians, but they could use a refresher on the economics of drug development. Several methodological flaws in the study lead the authors to underestimate drug-development costs.
Messrs. Prasad and Mailankody examined 10 publicly traded companies that secured their first-ever Food and Drug Administration approval between 2006 and 2015. They pulled data on companies’ research spending and revenues from annual financial reports filed with the Securities and Exchange Commission. These selection criteria are a joke. By looking at 10 companies that produced only one cancer drug each, the authors screened out big multinational corporations that had previously secured FDA approval for one or more drugs. Small biotech firms that hadn’t secured FDA approval for any treatments were also excluded.
The authors admit that the selection criteria are a “critical limitation.” No kidding: They only looked at 15% of all cancer drugs approved from 2006 to 2015, ignoring the other 85% of cancer therapies introduced that decade. This helped them “prove” their hypothesis.
The analysis also overlooks hundreds of millions of dollars of research spending at companies that never develop an FDA-approved medicine. Nine of every 10 publicly traded drug companies lost money in 2014, according to a 2016 International Trade Administration report. Most therapies don’t make it out of the lab and into clinical trials. Of those that do, only 12% are brought to market.
Those that defy the odds and win FDA approval don’t accurately represent the broader biopharmaceutical industry. Consider the success of these 10 drugs against those that are still going through clinical trials. Even if all of these companies’ other experimental drugs in the development pipeline failed, the success of this study’s 10 drugs would have resulted in an overall clinical approval success rate of 23%, twice the industry average.
Worse, five of the companies in question had purchased their drugs from smaller biotech firms. The authors didn’t count any of the research-and-development spending of these “nurturer” firms, only by the acquiring firm.
The other five drugs were developed entirely in-house—and the authors lowballed cost estimates for developing these drugs. Messrs. Prasad and Mailankody counted only two years of development costs before the first mention of the drugs in the medical literature. They figured this would accurately reflect preclinical costs, such as lab tests.
Their assumption is wrong. In reality, the initial, preclinical research period often lasts four years or more. And for four of the 10 drugs examined, companies started lab research at least seven years before the first mention of the drug in any published medical studies.
Drug development is much more expensive than the JAMA study suggests. More reliable is a November 2014 study from the Tufts Center for the Study of Drug Development. This more thorough examination estimates total research costs are about $2.6 billion for new cancer drugs. Politicians who advocate price controls undoubtedly will cite the JAMA study anyway. Never mind that government-imposed price caps would hamstring researchers and prevent the development of new treatments and cures.
In the past 17 years, biopharmaceutical companies have invented more than 550 FDA-approved medications. More than 800 experimental cancer drugs are currently under development at companies of all sizes, from tiny biotechs to giant multinationals. By misinforming readers, the JAMA study undermined the great work that drug companies are doing today.
Mr. Pitts, a former FDA associate commissioner (2002-04), is president of the Center for Medicine in the Public Interest
A Flawed Study Depicts Drug Companies as Profiteers
Peter J. Pitts
Even the authors admit their selection criteria are a ‘critical limitation.’ That’s an understatement.
Are drug companies ripping off cancer patients? Of course they are, suggests a much-hyped study published last month in the journal JAMA Internal Medicine. The truth is more complicated.
Drug companies receive a staggering return on investment “not seen in other sectors of the economy,” write Vinay Prasad of Oregon Health and Science University and Sham Mailankody of Memorial Sloan Kettering Cancer Center. They estimate that pharmaceutical firms spend $720 million on average to develop a single cancer drug, while the average cancer therapy generates sales of $6.7 billion.
The editors at JAMA are brilliant physicians, but they could use a refresher on the economics of drug development. Several methodological flaws in the study lead the authors to underestimate drug-development costs.
Messrs. Prasad and Mailankody examined 10 publicly traded companies that secured their first-ever Food and Drug Administration approval between 2006 and 2015. They pulled data on companies’ research spending and revenues from annual financial reports filed with the Securities and Exchange Commission. These selection criteria are a joke. By looking at 10 companies that produced only one cancer drug each, the authors screened out big multinational corporations that had previously secured FDA approval for one or more drugs. Small biotech firms that hadn’t secured FDA approval for any treatments were also excluded.
The authors admit that the selection criteria are a “critical limitation.” No kidding: They only looked at 15% of all cancer drugs approved from 2006 to 2015, ignoring the other 85% of cancer therapies introduced that decade. This helped them “prove” their hypothesis.
The analysis also overlooks hundreds of millions of dollars of research spending at companies that never develop an FDA-approved medicine. Nine of every 10 publicly traded drug companies lost money in 2014, according to a 2016 International Trade Administration report. Most therapies don’t make it out of the lab and into clinical trials. Of those that do, only 12% are brought to market.
Those that defy the odds and win FDA approval don’t accurately represent the broader biopharmaceutical industry. Consider the success of these 10 drugs against those that are still going through clinical trials. Even if all of these companies’ other experimental drugs in the development pipeline failed, the success of this study’s 10 drugs would have resulted in an overall clinical approval success rate of 23%, twice the industry average.
Worse, five of the companies in question had purchased their drugs from smaller biotech firms. The authors didn’t count any of the research-and-development spending of these “nurturer” firms, only by the acquiring firm.
The other five drugs were developed entirely in-house—and the authors lowballed cost estimates for developing these drugs. Messrs. Prasad and Mailankody counted only two years of development costs before the first mention of the drugs in the medical literature. They figured this would accurately reflect preclinical costs, such as lab tests.
Their assumption is wrong. In reality, the initial, preclinical research period often lasts four years or more. And for four of the 10 drugs examined, companies started lab research at least seven years before the first mention of the drug in any published medical studies.
Drug development is much more expensive than the JAMA study suggests. More reliable is a November 2014 study from the Tufts Center for the Study of Drug Development. This more thorough examination estimates total research costs are about $2.6 billion for new cancer drugs. Politicians who advocate price controls undoubtedly will cite the JAMA study anyway. Never mind that government-imposed price caps would hamstring researchers and prevent the development of new treatments and cures.
In the past 17 years, biopharmaceutical companies have invented more than 550 FDA-approved medications. More than 800 experimental cancer drugs are currently under development at companies of all sizes, from tiny biotechs to giant multinationals. By misinforming readers, the JAMA study undermined the great work that drug companies are doing today.
Mr. Pitts, a former FDA associate commissioner (2002-04), is president of the Center for Medicine in the Public Interest
Are drug companies ripping off cancer patients? Of course they are, suggests a much-hyped study published last month in the journal JAMA Internal Medicine. The truth is more complicated.
Drug companies receive a staggering return on investment “not seen in other sectors of the economy,” write Vinay Prasad of Oregon Health and Science University and Sham Mailankody of Memorial Sloan Kettering Cancer Center. They estimate that pharmaceutical firms spend $720 million on average to develop a single cancer drug, while the average cancer therapy generates sales of $6.7 billion.
The editors at JAMA are brilliant physicians, but they could use a refresher on the economics of drug development. Several methodological flaws in the study lead the authors to underestimate drug-development costs.
Messrs. Prasad and Mailankody examined 10 publicly traded companies that secured their first-ever Food and Drug Administration approval between 2006 and 2015. They pulled data on companies’ research spending and revenues from annual financial reports filed with the Securities and Exchange Commission. These selection criteria are a joke. By looking at 10 companies that produced only one cancer drug each, the authors screened out big multinational corporations that had previously secured FDA approval for one or more drugs. Small biotech firms that hadn’t secured FDA approval for any treatments were also excluded.
The authors admit that the selection criteria are a “critical limitation.” No kidding: They only looked at 15% of all cancer drugs approved from 2006 to 2015, ignoring the other 85% of cancer therapies introduced that decade. This helped them “prove” their hypothesis.
The analysis also overlooks hundreds of millions of dollars of research spending at companies that never develop an FDA-approved medicine. Nine of every 10 publicly traded drug companies lost money in 2014, according to a 2016 International Trade Administration report. Most therapies don’t make it out of the lab and into clinical trials. Of those that do, only 12% are brought to market.
Those that defy the odds and win FDA approval don’t accurately represent the broader biopharmaceutical industry. Consider the success of these 10 drugs against those that are still going through clinical trials. Even if all of these companies’ other experimental drugs in the development pipeline failed, the success of this study’s 10 drugs would have resulted in an overall clinical approval success rate of 23%, twice the industry average.
Worse, five of the companies in question had purchased their drugs from smaller biotech firms. The authors didn’t count any of the research-and-development spending of these “nurturer” firms, only by the acquiring firm.
The other five drugs were developed entirely in-house—and the authors lowballed cost estimates for developing these drugs. Messrs. Prasad and Mailankody counted only two years of development costs before the first mention of the drugs in the medical literature. They figured this would accurately reflect preclinical costs, such as lab tests.
Their assumption is wrong. In reality, the initial, preclinical research period often lasts four years or more. And for four of the 10 drugs examined, companies started lab research at least seven years before the first mention of the drug in any published medical studies.
Drug development is much more expensive than the JAMA study suggests. More reliable is a November 2014 study from the Tufts Center for the Study of Drug Development. This more thorough examination estimates total research costs are about $2.6 billion for new cancer drugs. Politicians who advocate price controls undoubtedly will cite the JAMA study anyway. Never mind that government-imposed price caps would hamstring researchers and prevent the development of new treatments and cures.
In the past 17 years, biopharmaceutical companies have invented more than 550 FDA-approved medications. More than 800 experimental cancer drugs are currently under development at companies of all sizes, from tiny biotechs to giant multinationals. By misinforming readers, the JAMA study undermined the great work that drug companies are doing today.
Mr. Pitts, a former FDA associate commissioner (2002-04), is president of the Center for Medicine in the Public Interest.
Here’s the CNN headline, “In an attempt to reduce opioid use amid a nationwide abuse epidemic, insurance giant Cigna will no longer cover most OxyContin prescriptions in its group plans beginning January 1.”
Cigna has signed a value-based contract with Collegium Pharmaceutical for the drug Xtampza ER, an oxycodone equivalent with abuse-deterrent properties. According to Cigna’s Chief Pharmacy Officer Jon Maesner "Our focus is on helping customers get the most value from their medications -- this means obtaining effective pain relief while also guarding against opioid misuse.”
That’s fine, but there’s one fact that’s strangely absent – both drugs, Oxycontin and Xtampza ER are equally “abuse-deterrent.” Here’s another important fact – OxyContin was reformulated and in 2013 and became the first opioid with FDA-approved labeling describing abuse-deterrent characteristics. Once the poster-child for abuse, Oxycontin is now at or near the bottom of the “junkie-preferred” chart.
It’s important to understand that both products are formulated with properties designed to deter intranasal (snorting) and intravenous (injection) abuse, but that neither is abuse proof -- and one isn't "better" than the other.
What Cigna isn’t saying is that it’s customers will no longer have access to a range of FDA-approved products with abuse deterrent properties -- limiting a physician’s options to help patients and address the opioid crisis via more personalized, appropriate therapeutic choices.
So, why the switch from Oxycontin to Xtampza ER? Could it be that Cigna negotiated a better deal with Collegium than it had with Purdue Pharma (the manufacturer of Oxycontin)? Unfortunately, this decision appears to be more about pharmaceutical rebates than “guarding against opioid misuse.”
Alas, Cigna’s hyperbole has been met with silence when it comes to pricing transparency.
Cigna has signed a value-based contract with Collegium Pharmaceutical for the drug Xtampza ER, an oxycodone equivalent with abuse-deterrent properties. According to Cigna’s Chief Pharmacy Officer Jon Maesner "Our focus is on helping customers get the most value from their medications -- this means obtaining effective pain relief while also guarding against opioid misuse.”
That’s fine, but there’s one fact that’s strangely absent – both drugs, Oxycontin and Xtampza ER are equally “abuse-deterrent.” Here’s another important fact – OxyContin was reformulated and in 2013 and became the first opioid with FDA-approved labeling describing abuse-deterrent characteristics. Once the poster-child for abuse, Oxycontin is now at or near the bottom of the “junkie-preferred” chart.
It’s important to understand that both products are formulated with properties designed to deter intranasal (snorting) and intravenous (injection) abuse, but that neither is abuse proof -- and one isn't "better" than the other.
What Cigna isn’t saying is that it’s customers will no longer have access to a range of FDA-approved products with abuse deterrent properties -- limiting a physician’s options to help patients and address the opioid crisis via more personalized, appropriate therapeutic choices.
So, why the switch from Oxycontin to Xtampza ER? Could it be that Cigna negotiated a better deal with Collegium than it had with Purdue Pharma (the manufacturer of Oxycontin)? Unfortunately, this decision appears to be more about pharmaceutical rebates than “guarding against opioid misuse.”
Alas, Cigna’s hyperbole has been met with silence when it comes to pricing transparency.
Per this article from the Washington Post, it's important to note that "not doing additional clinical trials," as I was quoted as saying, does not mean ignoring a more regular and robust use of electronically collected and validated real world data to ascertain the performance of off-label use. The FDA is required by the 21st Century Cures act to develop standard protocols for the use of real world data -- and nowhere is this more crucial than in determining the safe and effective use of medicines via off-label prescribing.
Pressure mounts to lift FDA restrictions on off-label drugs
By Michael Ollove
When the Food and Drug Administration gives its okay for a new drug to be sold, it specifies the diseases or conditions for which the medicine has been approved. That does not mean doctors can’t prescribe that drug for other ailments. They do. All the time. And it’s perfectly legal.
But for decades drugmakers have been barred from promoting their drugs for uses that hadn’t gone through clinical trials. Worried about safety issues, the FDA has prosecuted numerous drugmakers for illegal promotion of off-label uses and extracted billions of dollars in fines and settlements.
Those restrictions could be giving way, perhaps in part because of the appointment of Scott Gottlieb as the new FDA commissioner in May. Before his nomination, Gottlieb, a physician and a resident fellow at the conservative American Enterprise Institute, advocated loosening the restrictions on off-label communications.
That’s exactly what Arizona did earlier this year when it became the first state to allow drugmakers to communicate directly with doctors and insurers about alternative uses of approved prescription drugs. Advocates for the loosening of the restrictions say they expect similar measures to be introduced in other state legislatures in the coming year.
These developments come on the heels of two legal cases in which federal district courts ruled that the First Amendment does not allow the FDA to prevent manufacturers from providing truthful information about their products to doctors.
Supporters say it makes sense to get rid of the restrictions on off-label drugs at a time when plenty of information and misinformation about prescription drugs is readily available to anyone with an Internet connection. And, they insist, who better to provide accurate facts about their products than their makers?
“We believe it’s a disservice to patients and physicians to prevent them from getting information from manufacturers who know their medicines best,” said Naomi Lopez Bauman, director of health-care policy at the Goldwater Institute, the libertarian think tank that devised the Arizona legislation and is promoting it in other states.
Bauman said she expects bills to be filed elsewhere in the coming year, but she refused to disclose which states Goldwater is targeting.
Many critics, however, remain firmly opposed to such efforts. “There have literally been dozens and dozens of examples of off-label uses of drugs encouraged by pharmaceutical companies in reckless ways that have led to substantial patient morbidity and mortality,” said Aaron Kesselheim, director of the Program on Regulation, Therapeutics and Law at Harvard Medical School.
Wide off-label use
Before a new drug can be sold in the United States, the FDA must affirm that it is safe and effective for specified uses, which are then described in the medicine’s labeling. But once a drug is approved, doctors are free to prescribe it for uses not specified in the labeling. That is because the FDA regulates products but not the practice of medicine.
Prescribing for off-label uses has become common. A 2013 study found that 30 percent of the prescriptions for oncology drugs were used for off-label purposes. Another found that 70 percent of a popular category of pediatric antipsychotic drugs were prescribed for purposes not cited in the FDA’s approval of those medicines, including, for example, for the treatment of attention-deficit/hyperactivity disorder.
Sometimes the off-label use of prescription drugs comes to be considered the best treatment for certain conditions. “For some cancer drugs, the best therapeutic use is for off-label purposes,” said Peter Pitts, president and co-founder of the Center for Medicine in the Public Interest, a nonprofit research and advocacy organization that is funded by the pharmaceutical industry.
One example is tricyclic antidepressants, a class of drugs that do not have FDA approval as treatment for nerve-related pain yet are considered by doctors to be the first choice of drugs for that purpose.
Nevertheless, a recent study published in the journal JAMA found a higher incidence of adverse drug effects from off-label use than from on-label use.
Pitts does not think the FDA should prohibit drugmakers from dispensing information that might be relevant to those off-label uses. “In fact, it’s almost irresponsible not to let them dispense that information as long as it’s truthful, accurate and not misleading,” he said.
Pitts and others say it is unreasonable to expect drug manufacturers to embark on additional clinical trials to demonstrate the safety and efficacy of already approved drugs for new purposes. That effort, like the original process, could cost drugmakers hundreds of millions of dollars in new testing and take years.
“If your drug is approved for X, why would you ever commit millions in additional testing to get approval for Y, when it’s already legal to use it for Y?” Pitts said.
Undermining the process?
The answer, according to opponents of loosening the restrictions, is public safety. If the FDA didn’t approve a drug for off-label uses, they say, that means the drugmaker hasn’t produced evidence to demonstrate the drug is safe and effective for those other uses.
“If you take it as your premise that an objective approval by someone with no financial interest is necessary to protect patients, then marketing a drug for unapproved uses is the same as marketing an unapproved drug,” said Allison Zieve, director of the litigation group at Public Citizen, a consumer watchdog group that opposes loosening the communication restrictions. To allow drugmakers to do so, she said, would undermine the whole system of FDA drug approval.
Zieve and other opponents point out that the limitations do not prevent the manufacturers from sharing peer-reviewed, scientific articles about off-label uses of their drugs with doctors and others. They just can’t promote off-label use in their marketing.
The Goldwater Institute — named for Barry Goldwater, who was a U.S. senator from Arizona — wrote the model law upon which the Arizona legislation was based. “It just seemed to me that this was a way to give physicians more information to help them treat their patients,” said Phil Lovas, a Republican who sponsored the bill while he was a member of the Arizona legislature.
The pharmaceutical industry did not formally lobby on behalf of the bill, although it has called for a revision in the FDA policies on communications about off-label uses.
Some critics say the Arizona law is meaningless because states cannot preempt federal law and because they don’t believe pharmaceutical companies will promote off-label uses unless given more direction from either the FDA, Congress or higher courts.
But the Goldwater Institute insists the federal law prohibiting drugmakers from promoting off-label use is unconstitutional. The group points to two rulings, one in 2012 and the other in 2015, in which federal courts in New York found that the FDA restriction violated the free-speech provisions of the First Amendment.
The Goldwater Institute also was behind another recent issue involving prescription drugs: what is called the “right-to-try” laws that give desperately ill patients the opportunity to receive promising experimental drugs that do not yet have FDA approval. Since 2014, 37 states have adopted right-to-try legislation, although critics too said at the time that those laws didn’t supersede federal law, which sharply restricts the dissemination of experimental drugs.
But the state laws did create momentum, which may have contributed to passage of a right-to-try bill in the U.S. Senate this summer. “I firmly believe state activity with right-to-try pushed it forward at the federal level,” said Lovas, who left the Arizona legislature in the spring to take a position in the Trump administration. “I’d like to see the same thing happen with this.”
It might. U.S. Reps. H. Morgan Griffith of Virginia and Brett Guthrie of Kentucky, both Republicans, filed separate bills this spring to ease the flow of information on off-label drugs. The House held a hearing on the bills in July but has taken no action since.
Pressure mounts to lift FDA restrictions on off-label drugs
By Michael Ollove
When the Food and Drug Administration gives its okay for a new drug to be sold, it specifies the diseases or conditions for which the medicine has been approved. That does not mean doctors can’t prescribe that drug for other ailments. They do. All the time. And it’s perfectly legal.
But for decades drugmakers have been barred from promoting their drugs for uses that hadn’t gone through clinical trials. Worried about safety issues, the FDA has prosecuted numerous drugmakers for illegal promotion of off-label uses and extracted billions of dollars in fines and settlements.
Those restrictions could be giving way, perhaps in part because of the appointment of Scott Gottlieb as the new FDA commissioner in May. Before his nomination, Gottlieb, a physician and a resident fellow at the conservative American Enterprise Institute, advocated loosening the restrictions on off-label communications.
That’s exactly what Arizona did earlier this year when it became the first state to allow drugmakers to communicate directly with doctors and insurers about alternative uses of approved prescription drugs. Advocates for the loosening of the restrictions say they expect similar measures to be introduced in other state legislatures in the coming year.
These developments come on the heels of two legal cases in which federal district courts ruled that the First Amendment does not allow the FDA to prevent manufacturers from providing truthful information about their products to doctors.
Supporters say it makes sense to get rid of the restrictions on off-label drugs at a time when plenty of information and misinformation about prescription drugs is readily available to anyone with an Internet connection. And, they insist, who better to provide accurate facts about their products than their makers?
“We believe it’s a disservice to patients and physicians to prevent them from getting information from manufacturers who know their medicines best,” said Naomi Lopez Bauman, director of health-care policy at the Goldwater Institute, the libertarian think tank that devised the Arizona legislation and is promoting it in other states.
Bauman said she expects bills to be filed elsewhere in the coming year, but she refused to disclose which states Goldwater is targeting.
Many critics, however, remain firmly opposed to such efforts. “There have literally been dozens and dozens of examples of off-label uses of drugs encouraged by pharmaceutical companies in reckless ways that have led to substantial patient morbidity and mortality,” said Aaron Kesselheim, director of the Program on Regulation, Therapeutics and Law at Harvard Medical School.
Wide off-label use
Before a new drug can be sold in the United States, the FDA must affirm that it is safe and effective for specified uses, which are then described in the medicine’s labeling. But once a drug is approved, doctors are free to prescribe it for uses not specified in the labeling. That is because the FDA regulates products but not the practice of medicine.
Prescribing for off-label uses has become common. A 2013 study found that 30 percent of the prescriptions for oncology drugs were used for off-label purposes. Another found that 70 percent of a popular category of pediatric antipsychotic drugs were prescribed for purposes not cited in the FDA’s approval of those medicines, including, for example, for the treatment of attention-deficit/hyperactivity disorder.
Sometimes the off-label use of prescription drugs comes to be considered the best treatment for certain conditions. “For some cancer drugs, the best therapeutic use is for off-label purposes,” said Peter Pitts, president and co-founder of the Center for Medicine in the Public Interest, a nonprofit research and advocacy organization that is funded by the pharmaceutical industry.
One example is tricyclic antidepressants, a class of drugs that do not have FDA approval as treatment for nerve-related pain yet are considered by doctors to be the first choice of drugs for that purpose.
Nevertheless, a recent study published in the journal JAMA found a higher incidence of adverse drug effects from off-label use than from on-label use.
Pitts does not think the FDA should prohibit drugmakers from dispensing information that might be relevant to those off-label uses. “In fact, it’s almost irresponsible not to let them dispense that information as long as it’s truthful, accurate and not misleading,” he said.
Pitts and others say it is unreasonable to expect drug manufacturers to embark on additional clinical trials to demonstrate the safety and efficacy of already approved drugs for new purposes. That effort, like the original process, could cost drugmakers hundreds of millions of dollars in new testing and take years.
“If your drug is approved for X, why would you ever commit millions in additional testing to get approval for Y, when it’s already legal to use it for Y?” Pitts said.
Undermining the process?
The answer, according to opponents of loosening the restrictions, is public safety. If the FDA didn’t approve a drug for off-label uses, they say, that means the drugmaker hasn’t produced evidence to demonstrate the drug is safe and effective for those other uses.
“If you take it as your premise that an objective approval by someone with no financial interest is necessary to protect patients, then marketing a drug for unapproved uses is the same as marketing an unapproved drug,” said Allison Zieve, director of the litigation group at Public Citizen, a consumer watchdog group that opposes loosening the communication restrictions. To allow drugmakers to do so, she said, would undermine the whole system of FDA drug approval.
Zieve and other opponents point out that the limitations do not prevent the manufacturers from sharing peer-reviewed, scientific articles about off-label uses of their drugs with doctors and others. They just can’t promote off-label use in their marketing.
The Goldwater Institute — named for Barry Goldwater, who was a U.S. senator from Arizona — wrote the model law upon which the Arizona legislation was based. “It just seemed to me that this was a way to give physicians more information to help them treat their patients,” said Phil Lovas, a Republican who sponsored the bill while he was a member of the Arizona legislature.
The pharmaceutical industry did not formally lobby on behalf of the bill, although it has called for a revision in the FDA policies on communications about off-label uses.
Some critics say the Arizona law is meaningless because states cannot preempt federal law and because they don’t believe pharmaceutical companies will promote off-label uses unless given more direction from either the FDA, Congress or higher courts.
But the Goldwater Institute insists the federal law prohibiting drugmakers from promoting off-label use is unconstitutional. The group points to two rulings, one in 2012 and the other in 2015, in which federal courts in New York found that the FDA restriction violated the free-speech provisions of the First Amendment.
The Goldwater Institute also was behind another recent issue involving prescription drugs: what is called the “right-to-try” laws that give desperately ill patients the opportunity to receive promising experimental drugs that do not yet have FDA approval. Since 2014, 37 states have adopted right-to-try legislation, although critics too said at the time that those laws didn’t supersede federal law, which sharply restricts the dissemination of experimental drugs.
But the state laws did create momentum, which may have contributed to passage of a right-to-try bill in the U.S. Senate this summer. “I firmly believe state activity with right-to-try pushed it forward at the federal level,” said Lovas, who left the Arizona legislature in the spring to take a position in the Trump administration. “I’d like to see the same thing happen with this.”
It might. U.S. Reps. H. Morgan Griffith of Virginia and Brett Guthrie of Kentucky, both Republicans, filed separate bills this spring to ease the flow of information on off-label drugs. The House held a hearing on the bills in July but has taken no action since.
Per FDA Commissioner Scott Gottlieb:
Complex drugs comprise high cost medicines like metered dose inhalers used to treat asthma, as well as some costly injectable drugs. These medicines generally have at least one feature that makes them harder to “genericize” under our traditional approaches. As a consequence, these drugs can face less competition. In some cases, costly, branded drugs that are complex drugs have lost their exclusivity, but are subject to no generic competition.
When considering the scope of complex drugs, people often first think of drug products where the active ingredient itself is complex. Glatiramer acetate injection, a drug used in the treatment of multiple sclerosis, is a good example. However, the terms “complex drug product” and “complex generic drug” are used to refer to a much larger and diverse group of drug products. In addition to drug products with complex active ingredients, or sites of action, complex drug products also include complex drug-device combination products.
Together, this diverse collection of drug products has one or more elements that are more complex than an average drug product. This complexity, in turn, means that the scientific and regulatory pathways for approval of generic versions of these drug products are not as well traveled by generic drug developers. In some cases, use of another established regulatory pathway may be appropriate to streamline development.
Bioequivalence for complex generic drugs can be challenging with complex drug products that can’t be easily measured in the blood, or when the drug’s therapeutic effect is delivered locally to a particular organ, rather than systemically, through the bloodstream. In other instances, showing active ingredient sameness can be challenging when the drug product contains an active mixture of components and not a single active molecule.
We recognize these problems and are taking a number of new steps to support the development of high quality ANDAs for complex generic drugs.
First, FDA is issuing a draft guidance to assist ANDA applicants and prospective ANDA applicants in creating and submitting pre-ANDA meeting requests, including meeting package materials, so FDA can give better advice to sponsors looking to develop complex generic drugs.
The guidance provides information on requesting and conducting product development meetings, pre-submission meetings, and mid-review cycle meetings with FDA. These meetings will allow for enhanced communication between generic drug applicants and FDA early in the generic drug development process, allowing for more efficient generic drug development, review, and approval pathways. We’ve found from analyzing our new drug program, that early and better meetings between FDA and sponsors can improve development timelines. We want to bring these same types of opportunities to developers of complex generics.
Second, we’re issuing a draft guidance to help applicants determine when submission of ANDAs for certain complex products, known as peptides, would be appropriate. Peptides are compounds made up of 40 or fewer amino acids, the building blocks of proteins. There are a number of branded medicines that are peptides, where exclusivity has lapsed, but these drugs face little or no competition. This new guidance applies to ANDAs for certain specific synthetic peptides, namely, glucagon, liraglutide, nesiritide, teriparatide, and teduglutide, that reference brand-name versions of these peptides manufactured using recombinant DNA technology.
We’re doing all of this without sacrificing the scientific rigor of the process one bit. A central aspect of our approach, and our efforts to spur innovation and generic competition, is focused on adopting more rigorous and sophisticated science, including sophisticated quantitative methods and computational modeling, in drug development, evaluation, and review.
We’ll soon release other important policies aimed at spurring competition to complex drugs. But we know that better guidance isn’t the only answer. Some drugs lack generic competition because they cannot be measured through traditional in vivo bioequivalence methods and there’s no efficient and convincing bioequivalence test method available.
In these instances, an applicant needs to conduct more extensive clinical endpoint testing to show bioequivalence of a generic drug to a brand-name drug. This can be burdensome and discourage generic product development. A further barrier to generic competition for certain complex drug products is the lack of established methods for showing the sameness of the active ingredient of a proposed generic drug to a brand-name drug for certain complex drugs.
Over the next year, FDA’s generic drug regulatory science program will work to identify gaps in the science and develop more tools, methods, and efficient alternatives to clinical endpoint testing, where feasible. To help with this task, we’re holding a series of important scientific workshops, beginning today, that will identify opportunities for complex generic drug development, discuss quantitative modeling approaches and principles and aid product-specific guidance development. The workshops will also help in the development of new analytical tools that will help overcome the unique development and regulatory challenges for demonstrating active ingredient sameness in complex products. We intend for these efforts to speed product development, reduce development costs, and improve access to these products.
Scott's full announcement can be found here.
Complex drugs comprise high cost medicines like metered dose inhalers used to treat asthma, as well as some costly injectable drugs. These medicines generally have at least one feature that makes them harder to “genericize” under our traditional approaches. As a consequence, these drugs can face less competition. In some cases, costly, branded drugs that are complex drugs have lost their exclusivity, but are subject to no generic competition.
When considering the scope of complex drugs, people often first think of drug products where the active ingredient itself is complex. Glatiramer acetate injection, a drug used in the treatment of multiple sclerosis, is a good example. However, the terms “complex drug product” and “complex generic drug” are used to refer to a much larger and diverse group of drug products. In addition to drug products with complex active ingredients, or sites of action, complex drug products also include complex drug-device combination products.
Together, this diverse collection of drug products has one or more elements that are more complex than an average drug product. This complexity, in turn, means that the scientific and regulatory pathways for approval of generic versions of these drug products are not as well traveled by generic drug developers. In some cases, use of another established regulatory pathway may be appropriate to streamline development.
Bioequivalence for complex generic drugs can be challenging with complex drug products that can’t be easily measured in the blood, or when the drug’s therapeutic effect is delivered locally to a particular organ, rather than systemically, through the bloodstream. In other instances, showing active ingredient sameness can be challenging when the drug product contains an active mixture of components and not a single active molecule.
We recognize these problems and are taking a number of new steps to support the development of high quality ANDAs for complex generic drugs.
First, FDA is issuing a draft guidance to assist ANDA applicants and prospective ANDA applicants in creating and submitting pre-ANDA meeting requests, including meeting package materials, so FDA can give better advice to sponsors looking to develop complex generic drugs.
The guidance provides information on requesting and conducting product development meetings, pre-submission meetings, and mid-review cycle meetings with FDA. These meetings will allow for enhanced communication between generic drug applicants and FDA early in the generic drug development process, allowing for more efficient generic drug development, review, and approval pathways. We’ve found from analyzing our new drug program, that early and better meetings between FDA and sponsors can improve development timelines. We want to bring these same types of opportunities to developers of complex generics.
Second, we’re issuing a draft guidance to help applicants determine when submission of ANDAs for certain complex products, known as peptides, would be appropriate. Peptides are compounds made up of 40 or fewer amino acids, the building blocks of proteins. There are a number of branded medicines that are peptides, where exclusivity has lapsed, but these drugs face little or no competition. This new guidance applies to ANDAs for certain specific synthetic peptides, namely, glucagon, liraglutide, nesiritide, teriparatide, and teduglutide, that reference brand-name versions of these peptides manufactured using recombinant DNA technology.
We’re doing all of this without sacrificing the scientific rigor of the process one bit. A central aspect of our approach, and our efforts to spur innovation and generic competition, is focused on adopting more rigorous and sophisticated science, including sophisticated quantitative methods and computational modeling, in drug development, evaluation, and review.
We’ll soon release other important policies aimed at spurring competition to complex drugs. But we know that better guidance isn’t the only answer. Some drugs lack generic competition because they cannot be measured through traditional in vivo bioequivalence methods and there’s no efficient and convincing bioequivalence test method available.
In these instances, an applicant needs to conduct more extensive clinical endpoint testing to show bioequivalence of a generic drug to a brand-name drug. This can be burdensome and discourage generic product development. A further barrier to generic competition for certain complex drug products is the lack of established methods for showing the sameness of the active ingredient of a proposed generic drug to a brand-name drug for certain complex drugs.
Over the next year, FDA’s generic drug regulatory science program will work to identify gaps in the science and develop more tools, methods, and efficient alternatives to clinical endpoint testing, where feasible. To help with this task, we’re holding a series of important scientific workshops, beginning today, that will identify opportunities for complex generic drug development, discuss quantitative modeling approaches and principles and aid product-specific guidance development. The workshops will also help in the development of new analytical tools that will help overcome the unique development and regulatory challenges for demonstrating active ingredient sameness in complex products. We intend for these efforts to speed product development, reduce development costs, and improve access to these products.
Scott's full announcement can be found here.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
