Are all men created "equivalent?

12/11/2014 09:20 AM |

From the pages of The Morning Consult:

Bioequivalence is going mainstream.

Ever since the FDA’s Pharmaceutical Science and Clinical Pharmacology Advisory Committee concluded in April of 2010 (in an 11-2 vote) that current bioequivalence standards are not sufficient for narrow therapeutic index (NTI) drugs, there’s been a growing focus and understanding on the fact that less variability equals better predictability.

(Narrow therapeutic index, per the FDA, means that, “small changes in blood concentration have the potential to result in serious therapeutic failures and/or serious adverse drug reactions.”)

Currently, the “sameness” of a brand product and a generic version is evaluated based on a two-treatment crossover study to prove bioequivalence, the aim being to show that the 90 percent confidence intervals of the geometric mean test/reference ratios for both maximum plasma concentration and the area under the plasma concentration-time curve fall within a range of 80 percent to 125 percent.

(“Equivalent” doesn’t mean the same thing as “identical.”)

“All men are created equivalent” just doesn’t have the same ring, does it?

This is an urgent public health issue – and it’s got momentum.

It’s too simplistic to call these “quality” problems. There’s a range from sub-standard Active Pharmaceutical Ingredient (API) and manufacturing issues, to excipient changes (excipients are the substances other than the pharmacologically active drug contained in a pill) and, most importantly, bioequivalence and bioavailability standards.

“We are losing control over what people are swallowing,” said Dr. Harry Lever, a cardiologist at the Cleveland Clinic who is trying to raise awareness of the matter among U.S. lawmakers. “Now, when a patient comes in who is not doing well, the first thing I do is look at their drugs and find out who makes it.”

Bioequivalence does not always equal therapeutic equivalence – and that’s especially true for Toprol XL. Recently two large Indian manufacturers, Wockhardt and Dr. Reddy’s Laboratories, have announced recalls over the last two months totaling more than 100,000 bottles of Toprol XL because their products were not dissolving properly — therefore probably not working as they should. The drug is a beta blocker that treats high blood pressure and heart ailments.

The issue of bioequivalence and therapeutic substitution will be at or near the top of the budget agenda in state capitols across the United States. NTI generic drugs, biosimilars and non-biologic complex drugs (NBCDs) are a medical option, but as every state in the union attempts to tighten its budget, requiring patients to use these follow-on products is an enticing, but incorrect and dangerous policy option. Placing short-term budgetary considerations before long-term patient well-being is pennywise and pound foolish, and is deleterious to both the public purse and public health. As an article in the Journal of Infection so aptly stated, “Nothing is more expensive than treatment failure.”

FDA’s recent draft guidances on bioequivalence for both generic and innovator products, as well as the move towards independent labeling for generic products are additional steps the agency has recently taken to address the issue of drug quality beyond safety and efficacy. And the implications for NTI generics, biosimilars and NBCDs is obvious.

(Something else to consider is for the FDA to report bioequivalence data in labels.)

The bioequivalence issue is clearly rising up the list of FDA priorities. Consider the agency’s action last week when it informed Mallinckrodt its methylphenidate hydrochloride tablets might not be therapeutically equivalent to Concerta, which is made by Johnson & Johnson ’s Janssen Pharmaceuticals Inc.

The FDA, in a statement, said the drug produced by Mallinckrodt may deliver the drug at a slower rate than another generic version of Concerta. As a result of its analysis, the FDA said the Mallinckrodt products are still approved and are eligible to be prescribed, but it no longer recommends them as an automatic substitution for Concerta.

But there’s a serious process issue that cannot be ignored. Mallinckrodt said the FDA informed the company that the change was based on new draft guidance for determining equivalency between the drugs that was published on November 6^th – but the guidance has an open comment period that runs through January 5th, 2015. The FDA said this change was based on the application of its new Draft Guidance for determining bioequivalence of methylphenidate hydrochloride products just published on November 6, 2014. Although the Draft Guidance has an open comment period through January 5, 2015, the agency nevertheless confirmed that this change would be reflected on November 13, 2014 in the on-line Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations.

That may or may not be the proper public health decision – but it certainly doesn’t seem fair relative to thoughtful public comment. Not surprisingly, Mallinckrodt is suing the U.S. Food and Drug Administration for “unlawful” reclassification.

This is not a trivial issue. Regulatory predictability is at the foundation of the problem – and is the keystone of the solution. Minus sound and timely guidance, companies will think twice about whether or not to proceed with generic copies of medicines with a narrower therapeutic index. And that equates to less competition – which results in higher prices. This is as true for NTI medicines as it is for biosimilars. The good news is that guidances exist. The same is not true (at least not yet) for NBCDs. That should be next on the agenda – especially as it relates to A/B ratings. After all, if there are going to four categories of biosimilars, each with its significant impact on therapeutic interchangability, shouldn’t there be a commensurate finesse for similarly complex non-biologics approved under the Hatch-Waxman generic approval process?

As my friend and colleague, Dr. Scott Gottlieb has written:

The complex drugs fall in a regulatory gap. FDA has tried to retrofit the “Hatch Waxman” generic drug law and policies that govern approval of small molecule drugs to these complex drugs, with sometimes troubling results. Regardless of the decision FDA makes with Copaxone, it remains clear that Congress and FDA alike need to re-examine the regulatory process when it comes to these intricate drugs.

The problem is that FDA has refused to define these complex drugs as distinct from normal, small molecule medicines. That has forced the agency to rely on less information in approving these complex copies than it probably would like. The agency’s desire to try and squeeze these complex drugs through its existing generic law approval pathway may have as much to do with political expediency as with good science. FDA is probably well aware that getting Congress to define a distinct category for these medicines, and give FDA proper tools, could be a heavy political lift. So FDA is doing what it often does: trying to massage its existing authorities and regulatory practices to fit novel challenges. But at what cost?

The good news is that the FDA recognizes the need for more specific, regular, and predictable standards. That’s precisely why the agency has asked industry to identify drug products that require explicit bioequivalence testing guidances.

Robert Lionberger, head of the FDA’s Office of Research and Standards, said the agency’s objective is to develop a product-specific BE guidance before a manufacturer files an ANDA for the drug in question.

That bad news, per a report in Drug Industry Daily, is that the agency has more than 1,200 product-specific guidances posted to aid ANDAs, leaving hundreds of potential generic targets without an FDA-sanctioned roadmap for development. Their absence has complicated the process of submitting successful ANDAs.

Is the NBCD pathway, for example, something that should be considered as part of the pending 21^st Century Cures legislation?

We are increasingly living in an n-of-1 world. Small is the new Big. We must think differently about bioequivalence on the front end and pharmacovigilance on the back-end. While we must continue to capture adverse event data, we must also strive to capture Substandard Pharmaceutical Events (SPEs). SPEs occur when a product does not perform as expected—perhaps because of API or excipient issues – or too broad of a bioequivalence range and issues relating to therapeutic interchangeability.

When it comes to 21st-century pharmacovigilance, we have to both broaden and narrow our views about bioequivalence to the patient level. Outcomes is so much more than a value-based reimbursement issue.

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Who Are The Most Powerful People in Healthcare?

12/10/2014 02:12 PM |

  I think people living with cancer will be a powerful political force in the years to come.   More powerful than the HIV community was in the 1980s.  This political force will right the wrongs and tear down the obstacles that have made progress against cancer slower than is scientifically possible.   I predict the new cancer advocacy will be the vanguard in reforming Obamacare, holding greedy health insurers to account and reducing the cost and time required to develop and access new medicines.  

There is a growing awareness that science of attacking cancer is reaching a critical mass and is producing a truly transformational approach to treatment: one that re-engineers our natural immune responses to do the job of not just killing cancer cells but teaches the remaining ones to start become healthy.    

There is a growing awareness that the way insurers have shifted cost to patients is discriminatory and that the claim that it’s a reaction to high prices is bogus. 

There is a growing recognition that the value new medicines yield must be measured in terms of every month of every life gained.   More people are alive today because each era of treatments keeps people alive longer for the next generation of therapies that improve and lengthen life even more.  

And there is a growing recognition that the pace of progress is too damn slow, too dependent on outdate scientific methods that require people dying of disease to be randomized to different treatments or different combinations of treatments in ways that have little to do with their unique and increasingly accessible biological differences.  

There is an increasing emphasis on improving the quality of life and the fact being treated for cancer does not mean being treated like a victim.   

And finally, people are increasingly aware that by sharing information more quickly about the real world experience with medicines is the most scientific and efficient way to cure cancer.

I am honored to be part of this courageous community of advocates, patients, scientists and biopharmaceutical companies that express their awareness with growing discontent with the status quo.   As Thomas Edison said: “Discontent is the first necessity of progress.”

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How do you say "biosimilar quality" in Hindi?

12/10/2014 09:32 AM |

At the same time that regulators in France, Germany, Belgium and Luxembourg are suspending the marketing approval of 25 generic drugs due to concerns over the quality of data from clinical trials conducted by India's GVK Biosciences, another Indian firm, Zydus Cadila, has launched a biosimilar of Adalimumab (an anti-TNF-α monoclonal antibody, which is approved in many countries for the treatment of inflammatory diseases, including rheumatoid arthritis, plaque psoriasis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease and ulcerative colitis.)

Bad timing and, perhaps, bad science.

The quality of Indian pharmaceuticals has come under fire this year, with regulators in Europe and the United States citing problems ranging from data manipulation to sanitation and banning the import of certain products from several firms. And, it should be noted, these violations are for generic drugs, not biosimilars.

French and German regulators are investigating drug approvals based on clinical trials meant to show that these generic drugs were equivalent to the original branded versions conducted by GVK Bio between 2008 and 2014.

A Zydus Cadila spokesman commented that, “This therapy will offer a new lease of life to millions in India who have not had access to this therapy so far.” But the reality is that their product is more likely to be aggressively marketed for export.

Most importantly is the question of quality – or lack thereof. As company’s ranging from biotech innovator Amgen to multinational generics manufacturer Sandoz struggle to fulfill the clinical requirements for an Adalimumab biosimilar, two obvious questions arise -- (1) What does Zydus Cadila know that large multinational manufacturers don’t; and (2) What do Indian regulators know that their counterparts in the US and the EU are struggling to understand?

To not aggressively ask these questions is to bury one’s head in the sand.

And here’s an even tougher question -- In order to boost pharmaceutical exports, are Indian regulators willing to license substandard products?

According to a May 2012 article in The Lancet,

“To say that India's drug regulatory authority, the Central Drugs Standard Control Organisation (CDSCO)-whose remit includes new drug approval, licensing of manufacturing facilities, and regulation of drug trials-is not fit for purpose seems a gross understatement.”

 “If I have to follow U.S. standards in inspecting facilities supplying to the Indian market,” G. N. Singh, India’s top drug regulator, said in an interview with an Indian newspaper, “we will have to shut almost all of those.”

Does that mean US standards are too high or that Indian ones are too low? Well, where you stand depends on where you sit. And if you’re sober and sitting up straight, the answer is obvious.

According to Dilip Shah, Secretary General of the Indian Pharmaceutical Alliance, some Indian manufacturers “doctor their data.” The solution? “Regulators should have regular liaison with manufacturers in India and China to explain to them how GMP works and that they don’t have to cheat.”

Feel better now?

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Missouri and PDMPs -- The Don't Show Me State

12/08/2014 07:38 AM |

The bad news is that Missouri is the only state that does not have a prescription drug monitoring program.

According to the New York Times, Missouri is the only state in America that has declined to keep a prescription drug database — the primary tool the other 49 states use to identify people who acquire excess prescriptions for addictive painkillers and tranquilizers, as well as the physicians who overprescribe them … Not having the database has not only hampered Missouri’s ability to combat prescription drug abuse, but also attracted people from neighboring states looking to stockpile pills and bring them home to take themselves or sell to others, according to law enforcement officials, legislators and data compiled by a prescription drug processing firm.

“Welcome to Missouri — America’s Drugstore,” said Dr. Douglas Char, an emergency room physician in St. Louis. “We aren’t just allowing abuse, we’ve created a business model for dealers.”

The good news is that Republican State Representative Holly Rehder is drafting a bill to change that.

The prescription drug-monitoring program (PDMP) is a database that collects information to let doctors and pharmacists lets doctors and pharmacists know a patient's prescription history. The program is used to reduce the amount of medications that are sold on the street and to reduce the risk of doctor shopping and abusing painkillers for nonmedical reasons.

One of the reasons the Show Me State has remained the Don't Show me State are unfounded concerns over privacy and Big Brotherism. Rehder’s proposed program would allow for only doctors and pharmacists to obtain the information and police officers would have to obtain a warrant to access the information.

Bob Twillman from the American Academy of Pain Management said the program helps identify not only if people are abusing drugs, but identifying their addiction so they can get professional help.

The bill previously passed in the House but has run into some roadblocks in the Senate, including St. Joseph Senator Rob Schaaf, who said the database would violate the privacy of citizens. After successfully sinking a 2012 version of the bill, Mr. Schaaf said of drug abusers, “If they overdose and kill themselves, it just removes them from the gene pool.”

Really?

Rehder said she is willing to work with Schaaf and others in order to get the bill passed.

Holly – don’t go lightly.

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ACA: Pennywise and Pound Foolish?

12/05/2014 10:17 AM |

From the pages of the Deseret News:

ACA should allow prescription drugs

President Barack Obama is fully vested in the claim that his Affordable Care Act is a success.

During a recent news conference, he pointed to the supposedly salutary effect the ACA has had on mitigating rising health care costs. "Health care inflation has gone down every single year since the law passed, so that we now have the lowest increase in health care costs in 50 years," Obama said.

Obama is right that health care inflation has slowed. The Centers for Medicare and Medicaid Services have reported exactly that for the past several years. But his praise is misplaced. Thanks is not due to the ACA but rather to increased access to prescription drugs, which help folks manage illnesses and stay out of the hospital. The ACA actually threatens to increase health care spending by keeping these vital prescription drugs out of reach for many Americans.

If policymakers are serious about slowing runaway health care costs, they need to ensure that sick people have good access to prescription medicines that will make them better.

Consider the example of Medicare Part D. In 2006, Medicare Part D expanded access and reduced the costs of prescription drugs for millions of Americans. The following year, prescriptions filled by Medicare beneficiaries jumped by 14 percent, and, as a result, the annual growth in spending per beneficiary dropped by almost half.

A new National Bureau of Economic Research study credited Part D coverage with an 8 percent drop in hospital admissions for seniors and around $1.5 billion in reduced hospital spending.

The Congressional Budget Office reached a similar conclusion in 2012, finding that spending on medical services dropped by 0.2 percent for every 1 percent increase in prescriptions filled.

In fact, failure to regularly take prescribed medications puts considerable strain on the health care system. A study from the Annals of Internal Medicine estimates that non-adherence already costs the health care system $100 billion to $289 billion a year. That includes avoidable hospitalizations, nursing home admissions and premature deaths.

Given the power of prescription drugs, the Obama administration should be pushing to increase their accessibility. Instead, the administration is actively working against them.

Since Medicare Part D began, the government has required insurers to cover drugs in six treatment areas. The Obama administration, however, proposed early this year to limit coverage of immunosuppressants, antidepressants and antipsychotic medicines for diseases like schizophrenia. The proposal caused an outcry from patients, health care providers and members of both political parties, and the administration scrapped the plan.

But now the Obama administration is doing damage elsewhere — by limiting prescription drugs through the health care exchanges created by the ACA.

Plans available through the exchanges often charge patients significant out-of-pocket fees to access needed prescription drugs. For moderate to low-income patients, these high costs may force them to miss prescriptions.

Insurance companies decide how to share costs with patients by using a tiered system. A patient who needs a drug in the lowest tier might have to pay only a $15 copay. But for those drugs in the highest tier, patients can pay as much as 40 percent of the actual cost of the drug, which can run up to tens of thousands of dollars.

Too many key medications on too many plans are now listed in the highest tier. A recent study from Avalere Health found that more than a fifth of all "Silver" Plans — the most popular coverage — require patients to pay 40 percent of the costs associated with seven classes of drugs. And 60 percent of Silver Plans placed all drugs for multiple sclerosis and rheumatoid arthritis on the highest cost-sharing level.

Just as expanded access to drugs reduces overall health care spending, restricting access drives up costs. Patients who can't readily afford to spend thousands of dollars on, say, their AIDS medication, will probably end up skipping doses. This non-adherence will increase hospitalization rates and overall health care spending.

If the Obama administration wants to put a brake on health care spending, it must preserve robust access to prescription drugs. The White House's attempts to limit prescription drug access in Medicare Part D are incredibly shortsighted. Instead, the administration should be doing all it can to ensure that more Americans have access to these vital drugs.

Peter J. Pitts, a former Food and Drug Administration associate commissioner, is president of the Center for Medicine in the Public Interest.

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HIV Impact With and WIthout Expensive New Medicines

12/02/2014 05:40 PM |

Yesterday was World AIDS Day.   In 1989, the first drugs to slow the progression of HIV were introduced.  They were attacked for being too expensive and showing no survival benefit.  According to critics then and now, it was a drug that did not deserve to be priced at $10K a year (about $20K in today's dollars).  Ditto next generation medicines. Alarms about the lifetime costs of therapy were raised. Only rarely did people look at the economic and social value of these new treatments.  

Here's a snapshot of what the impact HIV would have today on hospitalization, hospital costs and hospital deaths if we had listened to the naysayers.  Data for chart below is from Agency for Healthcare Research and Quality (AHRQ), based on data collected by individual States and provided to AHRQ by the States for the Clinical Classification Code for HIV   Read More & Comment...

High Cancer Drug Prices Are NOT Making Health Care Costs 'Unsustainable"

11/30/2014 11:54 PM |

Hagop Kantarjian and Peter Bach claim drug prices have doubled in the past decade, from an average of $5,000 per month to more than $10,000.

Eleven of the 12 cancer drugs the Food and Drug Administration approved for fighting cancer in 2012 were priced at more than $100,000 per year, double the average annual household income, according to a report by the Journal of National Cancer Institute.

Those claims are inaccurate at best and lies at worst. 

First,  as a Milliman study showss, the average cost of chemotherapy is about $25000.  A far cry from the $120K Kantarjian and Bacn assert.  

And while most of the new targeted cancer drugs are expensive, the average price -- including a standard discount and not counting any patient assistance -- is $5000 a month.  

The fact is,  cancer drugs, as a percentage of what people spend, of cancer care and total health care spending is small.   



An HHS study shows that prescription drugs, on average, cost people with cancer about $800 a year.   























 Kantarjian and others claim cancer drug prices cause bankruptcy.  Also misleading.   Cancer patients filing for bankruptcy comprise  2.2 percent of total filings. That's about 36,000 people a year.  The vast majority are low income and are unemployed.   That is a financially crushing combination for many more cancer patients beyond those who file for bankruptcy.  But drug prices are not to blame.

It is true that many more people are paying thousdands for cancer drugs but as my next blog reveals the Kantarjians and Bachs of the world deliberately ignore the role insurance comapne play in turning life saving drugs into a finanially sickening challenges.   More on that in my next post.  

 

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Has health care improved with reclassification of hydrocodone?

12/01/2014 08:48 AM |

This Sunday, the Boston Globe asked, “Has health care improved with reclassification of hydrocodone?”

Here’s the response of the dynamic Cindy Steinberg, policy chair for the Massachusetts Pain Initiative and national director of policy and advocacy for the US Pain Foundation:

No.

Severely restricting access to the most commonly used and highly effective pain medication is unjustly punishing the millions of law-abiding citizens who struggle to live with pain every day while doing little to solve the problem of abuse and addiction.

Hydrocodone combination products are effective for both acute and chronic pain and are useful and appropriate for a wide range of painful conditions and diseases. They have relatively few side effects and have been shown to have lower abuse potential than single entity opioids. In 2011, approximately 47 million Americans used hydrocodone analgesics for pain relief.

The number of Americans now living with pain is staggering. The Institute of Medicine has documented that there are more than 100 million living with chronic pain in this country. Ten million Americans live with chronic pain so severe that it has disabled them, and this number is expected to increase as the population ages.

When prescribed to individuals with pain severe enough to require these medications, the incidence of abuse and addiction is extremely low. For many with chronic pain, these medications mean the difference between a life worth living or not.

The new rules took effect Oct. 6. They require patients to obtain an original hard copy prescription for every 30 days of their medication — necessitating many more doctor visits — and then hand-delivering the script to their pharmacy. Doctors can no longer call in, fax, or electronically submit these prescriptions. Refills are prohibited.

According to Rebecca Fortelka, who suffers from cerebral palsy and several other chronic pain conditions writing in the Nov. 18 National Pain Report, hydrocodone combinations are one of the only pain medications she can tolerate. Soon after the new rules went into effect, she contacted her doctor’s office as she was running out of her medicine and needed a renewal. “My pain was spiraling out of control as I was rationing meds to prevent being out of them,” she wrote. It took her doctor’s office four weeks to get the hard copy prescription ready, leaving her to suffer.

Cutting off the supply of pain medication will not solve abuse and addiction. Those who are predisposed to the disease of addiction will turn to other medications or illicit substances, leaving those with the disease of chronic pain with fewer options. People with addiction disorders need better treatment for the disease of addiction, coordinated follow-up, and continuing support.

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Do High Priced Drugs Drive Up Healthcare Spending?

11/30/2014 10:24 AM |

Recent critics of cancer drug prices claim that the new higher priced medications drive up  total health care spending.  

In fact, the opposite is the case.  The evidence is overwhelming.   In fact, the addition of new medicines under Medicare's drug plan (Part D) has led to an absoute reduction in what's been spent on Medicare overall, $380 billion less to be exact.    A recent Health Affairs blog notes:  "Much attention in particular has focused on the remarkable slowdown in Medicare spending over the past few years, and rightfully so: Spending per beneficiary actually shrank (!) by one percent this year (or grew only one percent if one removes the effects of temporary policy changes).

Yet the disproportionate role played by prescription drug spending (or Part D) has seemingly escaped notice. Despite constituting barely more than 10 percent of Medicare spending, our analysis shows that Part D has accounted for over 60 percent of the slowdown in Medicare benefits since 2011 (beyond the sequestration contained in the 2011 Budget Control Act)."


































Critics will respond that the decline in Medicare spending was a function of the recession.  Not true.  "The recession and its aftermath appear to have had little effect on Medicare Part A and Part B spending; senior’s incomes are less influenced by economic downturns and the large majority of beneficiaries have supplemental coverage that shields them from most Part A and Part B cost-sharing. The primary analysis on the topic from CBO, in fact, found that only one-eighth of the slowdown in Parts A and B from 2007-2010 could be explained by factors related to the economy – and not through the usual channel of utilization impacts that take place in the private market."

Finally, some argue that the decline in spending was due to increased use of generic drugs on the part of Medicare consumers.  In fact,  most of the increase in Part D spending is the result of the use of new medicines for cancer, MS, diabetes and other drugs for the most expensive conditions Medicare patients deal with.  This is in line with studies conducted by Frank Lichtenberg and others showing that each dollar spent on new medicines reduces what would be spent on hospitals, doctors, etc. by $6.  

Looking at the price of a new medicine or what we spend on biopharmaceuticals in isolation is misleading.  Use of innovative  medicines should be looked at in terms of the impact it has on other medical spending and the lives of patients.   

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Why High Drug Prices Are Good For Us and the Economy

11/28/2014 03:00 PM |

This is Part One in a Series Entitled Why High Drug Prices Are Good For You.    Each blog will destroy a commonly held myth about health care costs and the blame people assign to new drugs for total health care spending.    Today we will look at the claim that "health care spending in the United States is rising at an unsustainable rate and faster than in Europe.  Following the example of Jonathan Gruber, I will try to use graphics and images that even someone like me can understand.    Here's the mythbuster Number One





Source: World Health Organization National Health Account database (see http://apps.who.int/nha/database/DataExplorerRegime.aspx for the most recent updates).  Read More & Comment...

Got HIV/AIDS? ACA doesn't care.

11/25/2014 07:21 AM |

According to a story in the Austin Statesman, Federal law doesn’t deliver HIV care as promised.” The ACA, per the story, “brought a lot of hope … but the law didn’t live up to expectations” because … “the plans on the federally created health insurance exchange, the Internet-based marketplace where consumers can compare and buy health plans, didn’t offer affordable ways to buy the life-saving medications” or allow patients to see “physician with expertise in HIV and AIDS.

Carl Schmid, the deputy executive director at the David Powell Clinic AIDS Institute, blamed insurance companies that offer plans that he said discriminate against HIV and AIDS patients and require huge out-of-pocket payments for their expensive medications.

“They are designing their benefits in such a way to dissuade people with HIV and other conditions from choosing their plans,” he said, “and that’s against the law.” Schmid’s national public policy group filed a complaint with the Office of Civil Rights in the U.S. Department of Health and Human Services. The case is pending.

David Wright, one of the first physicians in Central Texas to treat AIDS patients, said, “For a lot of patients, it actually created more barriers. It’s kind of overwhelming.”

Peter Pitts, a former U.S. Food and Drug Administration official and current president of the Center for Medicine in the Public Interest, echoed Wright’s assessment. He said before the law’s rollout, the standard talking point of proponents was that people shouldn’t have to choose between food or medicine.

“Unfortunately not only did the ACA not solve that problem, it made it worse,” Pitts said. “That’s shameful.”

The complete story can be found here.

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Process and Innovation

11/24/2014 11:47 AM |

One of the often-overlooked benefits of biosimilars is that it will drive innovation in manufacturing. Competition is the mother of invention.

Or, in the case of Amgen, reinvention. They’ve just launched a biologics manufacturing facility in Singapore that required one-quarter of the capital investment of a conventional operation, will operate one-third cheaper and took half the time to build.

(The plant will manufacture Prolia and Xgeva at a site that at 120,000 square feet is 80% smaller than a comparable conventional facility.)

When the company announced deep job and cost cuts in July, including at manufacturing facilities in Colorado and Washington, Amgen CEO Robert Bradway said that the company would be "exiting 20-year-old manufacturing technologies and continuing to invest in what we think are state-of-the-art, cutting-edge technologies that will enable us to rationalize and, we think, make product more reliably and more cost effectively.”

And, while there are yet many regulatory hurdles to leap, this is an excellent example of an innovator working to stay competitive in the age of biosimilars.

According to a report in Fierce Pharma, other drug makers, like GlaxoSmithKline are building plants utilizing the technology and Singapore appears to be the place to build them. GSK is working on a $50 million continuous manufacturing plant in Singapore that CEO Andrew Witty said will be 100 square meters instead of the usual 900 and so result in a "massive reduction in capital deployment" reducing costs by about 50%

As Eli Lilly & Co. CEO John Leichleiter said, "Creating and maintaining the conditions for innovation to flourish is challenging and complicated work - work that is never finished.”

But, the big question remains – will better and less costly manufacturing technologies (assuming they are approved by leading global regulators) lead to lower costs? More specifically, will it make off-patent biologics more price competitive with their biosimilar cousins?

Stay tuned.

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Important Victory in Opioid Abuse Deterrence

11/20/2014 01:37 PM |

There are few "eureka!" moments in healthcare.  Innovations are often incremental -- but doesn't make them any less important. Advances in abuse-deterrent opioids are no exception. Here's an advance important enough for an FDA press release. FDA approves extended-release, single-entity hydrocodone product with abuse-deterrent properties

The U.S. Food and Drug Administration today approved Hysingla ER (hydrocodone bitartrate), an extended-release (ER) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Hysingla ER has approved labeling describing the product’s abuse-deterrent properties consistent with the FDA’s 2013 draft guidance for industry, Abuse-Deterrent Opioids – Evaluation and Labeling. Hysingla ER has properties that are expected to reduce, but not totally prevent, abuse of the drug when chewed and then taken orally, or crushed and snorted or injected. The tablet is difficult to crush, break or dissolve. It also forms a viscous hydrogel (thick gel) and cannot be easily prepared for injection. The FDA has determined that the physical and chemical properties of Hysingla ER are expected to make abuse by these routes difficult. However, abuse of Hysingla ER by these routes is still possible. It is important to note that taking too much Hysingla ER, whether by intentional abuse or by accident, can cause an overdose that may result in death. “While the science of abuse deterrence is still evolving, the development of opioids that are harder to abuse is helpful in addressing the public health crisis of prescription drug abuse in the U.S.,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “Preventing prescription opioid abuse is a top public health priority for the FDA, and encouraging the development of opioids with abuse-deterrent properties is just one component of a broader approach to reducing abuse and misuse, and will better enable the agency to balance addressing this problem with ensuring that patients have access to appropriate treatments for pain.” Hysingla ER is not approved for, and should not be used for, as-needed pain relief. Given Hysingla ER’s risks for abuse, misuse and addiction, it should only be prescribed to people for whom alternative treatment options are ineffective, not tolerated or would be otherwise inadequate to provide sufficient pain management. As a single-entity opioid, Hysingla ER does not carry the serious liver toxicity risks associated with hydrocodone combination products containing acetaminophen. The FDA encourages health care professionals to review and consider all available information as part of their decision-making when prescribing opioid analgesics. Strengths of Hysingla ER contain 20, 30, 40, 60, 80, 100 and 120 milligrams (mg) of hydrocodone to be taken every 24 hours. Doses of 80 mg per day and higher should not be prescribed to people who have not previously taken an opioid medication (opioid non-tolerant). While Hysingla ER contains larger amounts of hydrocodone compared to immediate-release hydrocodone combination products, the range of tablet strengths of Hysingla ER is comparable to existing approved ER opioids.  The safety and effectiveness of Hysingla ER were evaluated in a clinical trial of 905 people with chronic low back pain. Additional data from studies conducted in laboratories and in people demonstrated the abuse-deterrent features of Hysingla ER for certain types of abuse (oral, snorting and injection). The most common side effects of Hysingla ER are constipation, nausea, fatigue, upper respiratory tract infection, dizziness, headache and drowsiness (somnolence).  The FDA is requiring postmarketing studies of Hysingla ER to assess the effects of the abuse-deterrent features on the risk for abuse of Hysingla ER and the consequences of that abuse in the community. In addition, Hysingla ER is part of the ER/LA Opioid Analgesics Risk Evaluation and Mitigation Strategy (REMS), which requires companies to make available to health care professionals educational programs on how to safely prescribe ER/LA opioid analgesics and to provide Medication Guides and patient counseling documents containing information on the safe use, storage, and disposal of ER/LA opioids. Hysingla ER is manufactured by Stamford-based Purdue Pharma L.P. For more information: •       FDA Approved Drugs: Questions and Answers •       FDA: Opioid Medications

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Grubernomics

11/20/2014 12:52 PM |

Grubernomics:  Economic analyses that are shielded from criticism and cited to the exclusion of other viewpoints in media outlets because they confirm existing biases.  

Here's why Jonathan Gruber was at once so prominent and arrogant:  He knew his audience wouldn't challenge him and critics would have no outlets to offer alternative research in the mainstream media, blogosphere, policy circles and academic publications.  In short, Gruber, like many liberal economists who are self-pronounced health economists,  had a monopoly.    The fact that Gruber received NIH money to study part D right after the election and White House cash to confirm that Obamacare would boost insurance enrollment, save money and improve health AND was flacking for Obamacare was not considered a conflict.  

Compare his treatment to that of Joseph DiMasi, another leading economist who studies the economic and opportunity costs of developing drugs.  DiMasi's critics have what amounts to an open mike in the media.  Academic publications have allowed critics to assail his research without any evidence or economic analyses.  DiMasi's research credibility is attacked as suspect because pharmaceutical companies provided support to the Tufts Center for the Study of Drug Development, where he heads up economic research.   But above all, DiMasi is dissed because his research -- which shows that drug development is costly because it's risky and sometimes done inefficiently --  doesn't fit the liberal narrative that drug companies sell useless drugs at outrageous prices because of monopolies and their ability to bribe doctors and the FDA.    


So Grubernomics can only survive if other viewpoints are systematically silenced or suppressed while media outlets, economic conferences, etc give the Gruber-views exalted status/

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PCMA on FDA and Biosimilars: Wrong, Wrong, and Wrong

11/20/2014 09:29 AM |

According to a report in Pharmtech.com:

“The Pharmaceutical Care Management Association (PCMA), an organization that represents the nation's leading pharmacy benefit managers (PBMs), which administer prescription drug plans for over 210 million Americans, released a new white paper investigating FDA’s influence on drug prices and competition in the pharmaceutical marketplace. The PCMA argues that competition within branded drugs is undervalued in FDA priorities and that FDA’s structures and regulations fundamentally hinder competition.”

The report's bias and ignorance can be summed up via this segment, “Without a statutory and regulatory agenda for the FDA that carefully examines the agency’s effect on pharmaceutical competition, some consumer welfare may be unnecessarily lost.”

Note to PCMA -- the FDA does not factor issues such as "competition" into it's regulatory calculations. Facts cannot be ignored because they are inconvenient.

The report takes specific aim at the FDA’s biosimilar pathway development process, stating that the delay in final guidance has “thwarted the development of a U.S. biosimilars industry—thus preventing the savings that competition would generate.” The report also calls out nomenclature issue for biosimilars as a potential impediment to the utilization of these products, and could also reduce the probability that drug makers would pursue a biosimilar for a product.

Wrong, wrong, and wrong.

Wrong that guidance should be rushed. (Isn’t it more important to get it right?) Wrong that discrete nomenclature will in any way deter use. (Isn’t it more important to ensure safety?) Wrong that manufacturers will decide to walk away because “it’s hard.” (Isn’t that table stakes?)

Speaking of transparency, it’s important to note that PBMs, such as Express Scripts, have a vested interest in keeping drug costs low. The PBM industry has largely supported the biosimilar movement from an early stage, as their utilization could produce an estimated 15% to 20% savings from innovator drug prices. This white paper screams, “cost over care.” According to Express Scripts President George Paz, “The cheapest drugs is (sic) where we make our profits.” (In 2008, Express Scripts agreed to pay $9.3 million to 28 states and $200,000 in reimbursement to consumers to settle lawsuits that accused the company of deceptive business practices in allegedly overstating the economic benefits to consumers of switching to certain drugs.)

Here’s the conclusion of the PharmaTech article:

“I believe the intent of Congress in providing a biosimilar pathway is to allow greater access through increased competition,” Peter Pitts, president of the Center for Medicine in the Public Interest and former FDA associate commissioner, told BioPharm International in a call. “The FDA’s job is to provide a pathway that’s transparent and predictable to allow enough companies to get into the game. If FDA doesn’t do that, it isn’t fully representing the intent of the legislation.”

Pitts believes FDA is doing the best job that it can, given the circumstances. “The creation of biosimilar regulations has to be a thoughtful and evolutionary process. The agency wants to make sure it’s as comprehensive as possible to create a level playing field.” Pitts adds, “The same proposition to transparency is relevant to nonbiologic, complex drugs as well, such as Lovenox.”

The complete PharmaTech article can be found here.

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Joe vs. the Volcano

11/19/2014 07:39 AM |

Much chatter about the Tuft’s Center’s new number for the cost of drug development.

Here’s the thoughtful comment from those lovely folks at Médecins Sans Frontières :

“The pharmaceutical industry-supported Tufts Center for the Study of Drug Development claims it costs US$2.56 billion to develop a new drug today; but if you believe that, you probably also believe the earth is flat.”

NGO’s can poo-poo the important work of Joe DiMasi and crew this as much as they like – but serious analysis can’t just be tsk-tsked away by using the “industry-supported” evasion.

Here’s the news – and it’s important.

Tufts Center for the Study of Drug Development Releases New Data on the Average Cost to Develop a New Medicine

The Tufts Center for the Study of Drug Development released new research on the average cost of drug development.  The research conducted by Joseph DiMasi, Tufts Center for the Study of Drug Development, Henry Grabowski, Department of Economics, Duke University, and Ronald Hansen, William E. Simon School of Business, University of Rochester. 

The estimates are based on research and development (R&D) costs for 106 randomly selected new drugs (87 small molecule drugs and 19 biologic medicines) obtained from a survey of 10 pharmaceutical firms The methodology used is consistent with prior research.  The studies use compound-level data on the cost and timing of development for a random sample of new drugs first investigated in humans and annual company pharmaceutical R&D expenditures obtained through surveys of a number of pharmaceutical firms. The new compounds were first tested in humans anywhere in the world from 2005 and 2007 and development costs were obtained through 2013. ^[i]

The estimates represent the average cost of developing a new medicine, including the costs of the majority of compounds which do not make it through clinical trials, and the large cost of capital associated with the long-term investments required for drug discovery and development.

• The average R&D cost required to bring a new, FDA-approved medicine to patients is estimated to be $2.6 billion over the past decade (in 2013 dollars), including the cost of failures. When costs of post-approval R&D^[ii] are included the cost estimate increases to $2.8 billion. 
• Average R&D costs have more than doubled over the past decade.

*Previous research by same author estimated average R&D costs in the early 2000s at $1.2 billion in constant 2000 dollars (see J.A. DiMasi and H.G. Grabowski. "The Cost of Biopharmaceutical R&D: Is Biotech Different?" Managerial and Decision Economics 2007; 28: 469–479).  That estimate was based on the same underlying survey as the author's estimates for the 1990s to early 2000s reported here ($800 million in constant 2000 dollars), but updated for changes in the cost of capital.

• The overall probability of clinical success (i.e., likelihood drug entering clinical testing will eventually be approved) was estimated to be 11.83%--this is significantly lower than the rate of 21.5% estimated previously.
• While the length of the process did not contribute to increases in R&D costs, it remained a very large share (45%) of total capitalized costs.
• Factors contributing to rising R&D costs cited by the researchers include:

o   Increases in out-of-pocket costs for individual drugs are attributed to a range of factors including but not limited to increased clinical trial complexity and larger clinical trial sizes and a greater focus on targeting chronic and degenerative diseases.

o   Higher failure rates for drugs tested in human subjects. The researchers noted an increase in the proportion of projects failing early, before reaching more costly Phase III trials.

These findings reinforce the challenges and complexities related to drug development, including technical challenges as companies are often focusing their R&D where the science is difficult and the failure risks are also higher.

For more information, please see: http://csdd.tufts.edu/news  

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Pain advocates to Massachusetts Governor-Elect: "Listen up!"

11/18/2014 07:19 AM |

Pain patient advocate extraordinaire, Cindy Steinberg lays it on the line for Massachusetts Governor-Elect Charlie Baker.

Memo To Gov.-Elect: Include Pain Sufferers As You Seek Opiate Solution

By Cindy Steinberg


 Cindy Steinberg is the policy chair for the Massachusetts Pain Initiative and the national director of policy and advocacy for the U.S. Pain Foundation.

“Charlie Baker vows to tackle state opiate problem,” was the Boston Globe headline two days after Election Day.

It’s good to hear from our newly elected governor that he plans to take steps to curb the ongoing problem with illegal use of prescription medication in our state. There’s little doubt that too many lives are being harmed by drug abuse and addiction.

But in a quest to fix one problem, policymakers need to consider the potential unintended negative consequences for the patients for whom these medications are a lifeline.

Gov.-elect Baker said in that Globe interview that he plans to convene a coalition of lawmakers, health care providers and labor leaders to confront the opioid crisis in our state. Representatives of the pain community — an estimated 1.2 million Massachusetts residents live with chronic pain — must be included in these discussions as well.

For many with chronic pain, the right medications mean the difference between a life worth living or not.

But despite these legitimate needs, more and more I’m hearing from residents of our state who are unable to access treatment that their doctors say they need and that they depend on. These are not addicts; these are people who are trying to manage their lives with debilitating conditions such as cancer, diabetic neuropathy, sickle cell, daily migraine, fibromyalgia, severe back pain and many others.

These are not addicts; these are people who are trying to manage their lives with debilitating conditions such as cancer, diabetic neuropathy, sickle cell, daily migraine, fibromyalgia.

Not including members of the pain community in discussions about how these medications are prescribed, regulated and controlled marginalizes the lives of thousands of Massachusetts citizens who live with pain caused by a myriad of conditions and serious injuries.

There is not a silver bullet solution to solving the abuse of prescription drugs. We need to take a thoughtful, multifaceted approach to ensure that those who need pain medication have access to it, and that those who choose to abuse these medications are stopped. There is no group more invested in making sure that medications are responsibly controlled than members of the pain community.

Last legislative session, Massachusetts lawmakers did take a step forward: they passed legislation on medications specially formulated to deter abuse.

“Abuse deterrent formulations” are opioids with physical and chemical properties that prevent chewing, crushing, grating, grinding, or extracting, or contain another substance that reduces or defeats the euphoria that those susceptible to substance abuse disorders experience. The new law requires insurance companies to provide the same coverage for the new abuse deterrent formulations as non-abuse deterrents, and they are not permitted to shift any additional cost of these medications to patients. It makes doctors more able to prescribe these medications without pushback from insurance companies.

Abuse deterrent formulations are not the only solution, but they are a good first step in balancing the legitimate needs of pain patients with the need to reduce medication abuse.

Other efforts must also include more robust education of medical professionals and of consumers to keep the medication out of the hands of potential abusers in the first place. Government statistics show that 78.5 percent of those who abuse prescription pain medication did not obtain them from a doctor themselves.

As someone who personally suffers from debilitating chronic pain, I have firsthand experience with the myriad challenges faced each day by the millions of Americans with severe chronic pain. I encourage Governor Baker to work to eliminate improper use of prescription medications, while remembering the medical needs of the chronic pain community.

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FDA data at the base of the pharmacovigilance pyramid

11/17/2014 09:28 AM |

A new article in the DIA's Therapeutic Innovation and Regulatory Science journal discusses the pitfalls and potential for the FDA's openFDA program.

This past June, the FDA launched openFDA, a new initiative designed to make it easier for web developers, researchers, and the public to access large, important public health datasets collected by the agency.

The crowd-sourcing of adverse event data may or may not yield interesting results, but it’s a good place to start. It represents an opportunity for the agency to begin designing a more evolved approach to 21st-century pharmacovigilance.

To borrow a term from the nuclear disarmament discussion, 21st-century pharmacovigilance must work with its various colleagues to ‘‘trust, but verify.’’ Again, this fits hand-in-glove with the spirit of openFDA.

Access to data is important—but 21st-century pharmacovigilance must also take into consideration the realities of funding, existing staff levels and training programs, and existing regulatory authority. Perhaps creative public use of FDA data via openFDA will help develop not only new solutions but also awareness of the magnitude of the task at hand.

The full open FDA: An Open Question article can be found here.

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All you need is a dollar and a dream

11/14/2014 09:17 AM |

A new agreement will expand access to Pfizer’s contraceptive, Sayana Press, for Women Most in Need in the World’s Poorest Countries. But there's more to story.

Per the Pfizer press release, “Collaboration will help advance progress and support global efforts to increase access to voluntary family planning information, services and contraceptives by 2020.”

Together with the Bill & Melinda Gates Foundation and the Children’s Investment Fund Foundation, Pfizer has announced an agreement to expand access to it’s injectable contraceptive, Sayana Press (medroxyprogesterone acetate), for women most in need in 69 of the world’s poorest countries. Sayana Press will be sold for $1 per dose to qualified purchasers, who can help enable the poorest women in these countries to have access to the contraceptive at reduced or no cost.

John Young, President, Pfizer Global Established Pharma Business: “This is a great example of applying innovation to a Pfizer heritage product to help broaden access to family planning, Pfizer saw an opportunity to address the needs of women living in hard-to-reach areas, and specifically enhanced the product’s technology with public health in mind.””

The Pfizer/Gates/CIFF effort is a result of the July 2012 London Summit on Family Planning, which set an ambitious and achievable goal of providing an additional 120 million women in the world’s 69 poorest countries with access to voluntary family planning information and services by 2020.

John Young, “I’m so pleased with the leadership from the Bill & Melinda Gates Foundation, the Children’s Investment Fund Foundation and other collaborating organizations that are helping create a sustainable market through an approach that could be a model for other medicines.”

Bravo for Pfizer and partners. But the bigger story here is the creative redesign of legacy products for use in the developing world at low or no cost with NGO and other non-industry collaborators. It’s a model worth deeper investigation and broader implementation. Innovation comes in many forms.

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Super Gruber Saves Stupid Americans

11/13/2014 06:55 PM |

No one could explain Obamacare to stupid American votes... until a superhero from academia appeared. 







Yes,  Jonathan Gruber created a comic book character around his persona...  I guess that's less narcissistic than naming the ACA Grubercare...




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