Latest Drugwonks' Blog
The passage of the Generating Antibiotic Incentives Now (GAIN) provisions in the latest PDUFA agreement is being applauded for adding incentives like an additional five years of market exclusivity and priority review for qualifying antibiotics – but they may not be the game-changing incentives as some in the industry hoped.
High development hurdles for antibiotics, the availability of low-cost generics and reimbursement challenges for pricey new antibiotics are likely to keep most investors on the sidelines at least until big pharma starts to show more interest in the space.
The pharmaceutical industry, particularly at the top tier, has largely abandoned the therapeutic area because of development, regulatory and commercial challenges.
GAIN, which had been a pending stand-alone bill for years, was created as a partial solution to the dilemma, driven by groups like the Infectious Diseases Society of America, the Robert Wood Johnson Foundation and the Pew Health Group’s Antibiotics and Innovation Project as well as major companies in the space – what one lobbyist called the perfect storm of academia and industry, with industry using the thought leaders’ support to make it happen on the Hill. GAIN is intended to encourage development of new antibiotics as part of an effort to combat growing antibiotic resistance by providing incentives to companies developing drugs that target resistant pathogens.
One of the key challenges facing antibiotic drug developers is uncertainty in the approval pathway for antibiotics. One of the provisions in GAIN requires FDA to review antibiotic guidelines and update them where appropriate. The agency already has been working to update guidance for industry by type of infection, as required by the previous round of PDUFA, and has turned its efforts to complicated urinary tract infections, acute bacterial skin and skin structure infections, and community- and hospital- acquired pneumonia. Nonetheless, the clinical trial requirements, statistical analyses and endpoints in some cases are considered overly burdensome by many in the industry.
A more dramatic change to FDA’s approval requirements for antibiotics could spark a sea change in antibiotic R&D. Industry had pushed Congress to consider more aggressive changes that would reduce the clinical trial requirements for new antibiotics by allowing drug makers to study new drugs by pathogen rather than by indication, or only in the most severely ill patients, which would raise the threshold for safety and create a market for antibiotics similar to that for orphan drugs, where high-priced treatments are used in only a small subset of critically ill patients. IDSA asked Congress to consider such an approach, which it calls the Limited Population Antibacterial Drug mechanism.
Beyond the regulatory hurdles, generic antibiotics are widely available, posing reimbursement challenges for expensive new brands that do reach the market. Antibiotics for resistant pathogens are mainly used in hospitals so they face the added pressure of needing to secure placement on hospital formularies. On top of all that, antibiotics are prescribed for short-course therapy, generally just a matter of days, which limits their sales potential compared to chronic treatments, and in turn, limits a company’s return on investment.
The increasing prevalence of drug resistant pathogens means there is a clear need for new agents – and a significant market opportunity for drugs that can fight resistant strains and demonstrate a compelling pharmacoeconomic value story in the process, mainly by reducing the length of time patients are required to stay in the hospital. Almost two million Americans per year develop hospital-acquired infections resulting in 99,000 deaths, according to the Centers for Disease Control and Prevention. Sepsis and pneumonia alone killed nearly 50,000 Americans in 2006 and cost the health care system more than $8 billion.
How much antibiotic developers will benefit from the GAIN provisions depends on the molecules in development. The five years of additional market exclusivity, which comes on top of the five years of exclusivity already granted to brand manufacturers through Hatch-Waxman, is a big incentive but only in cases where patent protection doesn’t run in parallel.
My question is: so what? Has the Obama administration already raised premiums for about 1 in 15 seniors because the are wealthier? Yes. Will premiums go up over all in old style Medicare? Yes. Are co-pays in real dollars increasing across the board? Yes.
Meanwhile, here's what GAO said about Medicare advantage:
"Enrollment is up for Medicare Advantage plans, the private plan alternative to Medicare's traditional fee-for-service program, and premiums for beneficiaries are down, according to a report from the Government Accountability Office (GAO).
The GAO report, released December 1, found enrollment in Medicare Advantage plans increased by about 6%, from 7.9 million to 8.4 million beneficiaries, from April 2010 through April 2011, and the premiums seniors paid for these plans decreased 14%, saving them nearly $50 million. The average monthly premium decreased from $28 to $24 (http://tinyurl.com/7jf2cxp)."
Let's set aside the fact that most seniors in old style Medicare have supplemental insurance that pays for everything else Medicare doesn't pay for. The fact that seniors are increasingly shifting to a more competitive -- Ryan-Wyden-like -- Medicare that offers more and charges less is a good thing. Right? The proponents of single payer Medicare want to take away that existing choice and not expand it. And that's good?
Claiming that seniors would have to pick up the cost of lower priced Medicare plan is not just incorrect factually. It is the opposite of true.
Good omnibus PDUFA V article in the August issue of Nature Biotechnology.
Here’s the opening paragraph:
After months of broad discussion followed more recently by narrower negotiations among legislators, late in June the US House of Representatives and Senate passed the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA), also known as the Prescription Drug User Fee Act V (PDUFA V). With wide bipartisan majorities, President Barack Obama signed FDASIA into law on July 9, ahead of looming deadlines. Whereas some are concerned that Congress sidestepped key issues in its haste to pass the legislation, industry has generally welcomed the new law, particularly its implications for research on treatments for rare diseases.
And some selected quotes:
In terms of fostering product development for rare diseases, FDASIA encapsulates “certainly the strongest language to date, but it's not that strong,” says Peter Pitts, president of the Center for Medicine in the Public Interest in New York. Moreover, the development and review of such products “can't be expedited until the agency becomes more transparent about its risk-benefit analysis...and really explains its decisions so that they can be replicated. We need the agency to be more predictable, even if its heart is in the right place.”
More generally, Pitts says, “I give this version of PDUFA only a gentleman's B. It could have been better.” For one thing, the new law mandates only that FDA work toward developing a “risk-benefit grid” instead of setting a specific date to complete this as well as other comparably challenging projects, he says. “The agency agreed to hold meetings, and it's good to talk. But it won't get to the right place as soon as it might.”
Pitts also points out that language in the new law will not make it easy to “hold [FDA] feet to the fire.” However, on the plus side, “Congress recognized the need for more regular oversight on technical aspects of regulation,” he says. “It's one thing to have hearings on politically expedient issues, but rarely does Congress take on the sophisticated but more boring aspects of drug regulation.”
The article also offers a nice table of PDUFA V highlights:
FDASIA reforms to FDA
* Accelerated Approval: Fast Track designation and accelerated approval for “a broad range of serious or life-threatening diseases or conditions”
* Advisory Committee Conflicts: No cap on conflict-of-interest waivers for advisory committee members
* Breakthrough Therapies: Expedited development and review of drugs for serious and/or life-threatening diseases that show major improvement over the standard of care in phase 1/2 trials
* Biosimilars Performance Goals: Commitment to process 70% of original biosimilar biological product application submissions within 10 months of the receipt date in 2013 (up to 90% in 2017)
* Communication Training: Staff at CDER and CBER to better communicate with drug development teams and manufacturing. Independent auditors to evaluate interactions between sponsors and FDA in discussions on labeling, REMS and other potential issues before submission and during review. FDA to consult with patients during product development and review and to host four meetings with patient groups per year in different diseases
* Critical Path Appropriation: $6 million annually for FY13–FY17 to promote public-private partnerships
* Drug Review Timelines: Extends by two months the PDUFA deadlines for Standard and Priority Review of NMEs and original BLAs
* Foreign Clinical Trials: Encourages collaboration with European and Asian regulators to prevent duplicative trials
* Guidances: FDA to issue guidance on development of abuse-deterrent drugs and on online promotion of regulated products, including social media. Sixty days before issuing any draft or final guidance on laboratory-developed tests, FDA must notify Congress
* Pediatrics: Formalizes the Best Pharmaceuticals for Children Act and Pediatric Research Equity Act and extends Priority Review voucher program to rare pediatric diseases
* Qualified Infectious Disease Products: Priority review and additional five years of exclusivity for novel anti-infective drugs against pathogens with “potential to pose a serious threat to public health”
* Rare Disease Experts: FDA to establish list of rare disease experts whom FDA may consult
The complete Nature Biotechnology article can be found here.
And speaking of fast track authority, Representative Brian Bilbray (R, CA) has drafted “The Patient Choice Act,” which would amend PDUFA V and provide a must swifter fast tract for critical and life-saving medicines.
Under “PROVISIONAL APPROVAL FOR ADEQUATELY SAFE FAST TRACK PRODUCTS” the draft bill reads:
Subject to the requirements of this subsection, if the Secretary determines that a drug that is designated as a fast track product under this section is adequately safe, the Secretary shall grant provisional approval and the drug may be introduced into interstate commerce on or after the date such provisional approval is granted.
Interestingly, all the power (per the draft language) rests with “the Secretary,” not the FDA. Considering the highly disturbing recent Plan B precedent – do we really want fast track approval authority residing with the Secretary of Health and Human Services?
Mr. Bilbray’s draft bill can be found here.
It is likely the last place you will ever see it.
Interesting article in the Lancet (Volume 380, Issue 9841, Pages 611 - 619, 11 August 2012 doi:10.1016/S0140-6736(12)60861-7), Hypertension in developing countries.
Here’s the summary:
Data from different national and regional surveys show that hypertension is common in developing countries, particularly in urban areas, and that rates of awareness, treatment, and control are low. Several hypertension risk factors seem to be more common in developing countries than in developed regions. Findings from serial surveys show an increasing prevalence of hypertension in developing countries, possibly caused by urbanisation, ageing of population, changes to dietary habits, and social stress. High illiteracy rates, poor access to health facilities, bad dietary habits, poverty, and high costs of drugs contribute to poor blood pressure control. The health system in many developing countries is inadequate because of low funds, poor infrastructure, and inexperience. Priority is given to acute disorders, child and maternal health care, and control of communicable diseases. Governments, together with medical societies and non-governmental organisations, should support and promote preventive programmes aiming to increase public awareness, educate physicians, and reduce salt intake. Regulations for the food industry and the production and availability of generic drugs should be reinforced.
Common sense? Not to everyone. It seems that members of uncivil society are somewhat perturbed since they prefer to focus on evil multinational corporations (MNCs) and patents as the key public enemies of public health in the developing world. They become defensive whenever issues like governments buying poor quality generics comes up, or the use of counterfeits, or the inconvenient fact that in Africa, 99% of all essential drugs are off patent or were never patented, but millions of patients don't have reliable access to them -- which puts the spotlight back on generics companies, kleptocratic governments and the failures of their health systems.
Uncivil society groupies appear reluctant to delve into the factors behind why millions of people in Africa and other LDCs don't have access to non patented, off patented, legally generic (and reliably high quality) essential drugs in Africa --but they'll devote gallons of ink to their claims about the predations of patents and MNCs.
Love, so to speak, among the ruins.
“That’s like a person already deeply in debt planning to buy a $50,000 car and finance it over ten years. Thanks to a dealer rebate, he pays $46,000. He has not reduced his debt by $4,000 but increased it by $46,000—plus interest.”
Read more here.
According to a new report in the Mayo Clinic Proceedings, many patients who are being treated with "off-label" drugs are unaware that the medications they have been prescribed by their doctor aren't being used in ways that would meet U.S. Food and Drug Administration approval, research shows.
Quelle surprise.
"Health care providers and patients should educate themselves about off-label drugs to weigh the risks and benefits before a physician prescribes one or a patient takes one,” says study lead author Dr. Christopher Wittich, an internal medicine physician at the Mayo Clinic in Rochester, Minn.
While this report states the obvious, the more important question is what are physicians telling their patients about the medicines they prescribe … and where is that information coming from.
Now that industry detailers are getting the cold shoulder and many inveigh against industry supported CME – wither knowledge about off label or, for that matter, on label indications?
It’s time for pharma detailers to start detailing the label – with such a detail aid being developed and approved by the FDA at launch.
The researchers also surmise that the high costs and lengthy process of obtaining FDA approval may deter drug companies from seeking approval for a new drug indication,.
How insightful.
Thomas Sowell said it best: " Prices are perhaps the most misunderstood thing in economics. Whenever prices are “too high” — whether these are prices of medicines or of gasoline or all sorts of other things — many people think the answer is for the government to force those prices down.
It so happens there is a history of price controls and their consequences in countries around the world, going back literally thousands of years. But most people who advocate price controls are as unaware of, and uninterested in, that history as I was in the law of gravity.
Prices are not just arbitrary numbers plucked out of the air or numbers dependent on whether sellers are “greedy” or not. In the competition of the marketplace, prices are signals that convey underlying realities about relative scarcities and relative costs of production.
Those underlying realities are not changed in the slightest by price controls. You might as well try to deal with someone’s fever by putting the thermometer in cold water to lower the reading.
Costs don’t go away because you refuse to pay them, any more than gravity goes away if you refuse to acknowledge it. You usually pay more in different ways, through taxes as well as prices, and by deterioration in quality when political processes replace economic process."
With that as a context, the upcoming Great Oxford Debate on drug prices seems to frame the issue in ways that go beyond the usual sophmoric level attained by policymakers and pundits...
Medicines and cost: what does GOD think?
UK NEWS | AUGUST 07, 2012
The problem with pharmaceutical policy is that it has become “over-focused to the point of obsession on issues of price and cost”, Professor Richard Sullivan, Director, Institute of Cancer Policy, will argue during the PharmaTimes Great Oxford Debate on 20 September at Oxford University, UK.
Professor Sullivan, who is also a member of the Kings Health Partners Integrated Cancer Centre, will join Eric Low, chief executive of Myeloma UK, and Stephen Whitehead, chief executive of the Association of the British Pharmaceutical Industry, at the prestigious annual debating event to propose that ‘patients have the right to the best medicines, regardless of cost’.
“The argument is not that we should pay whatever a company demands for a licensed medicine irrespective of how little benefit it bestows, rather that value is a much more subtle and complex issue than price alone,” Professor Sullivan says.
However, Professor Sullivan and co will have their work cut out for them as arguing against the motion, will be the Rt Hon Stephen Dorrell, MP, Chairman of the Health Select Committee, Professor Mike Pringle, President Elect of the Royal College of General Practitioners and Laura Weir, Head of Policy & Campaigns, MS Society and Chair, Patients Involved in NICE.
Says Dorrell: “I am strongly in favour of using the NHS budget to secure the best possible outcome for patients, but not in favour of a motion that appears to give treatments based on pharmaceutical products a higher priority than other forms of treatment, nor am I in favour of implying that decisions about healthcare should never be constrained by a real life requirement to decide about priorities.”
But isn’t it society’s moral and ethical duty to ensure that as new medicines are researched and developed they find their way to patients to prolong and improve patients’ wellbeing?
What do you believe? Do patients have the right to the best medicines under the NHS Constitution? If the best medicine is the NICE approved medicine, just what are patients' rights? Are those aged over 65 being discriminated against? Or is it that the NHS simply cannot afford the best medicines?
Join the debate on 20 September at the Oxford Union. For more details and to register your attendance click here or contact Hannah Smith hannah@pharmatimes.com or phone 0208 487 9119.
What? A large government entitlement program that comes in under budget and has high participant satisfaction rates?
That would be Medicare Part D. User satisfaction rates push 90 percent and the program’s cost is below budget, with an anticipated price tag of nearly $120 billion less than originally estimated over the next decade.
And here’s another gold to add to the Part D Olympic medal count – according to HHS, Medicare beneficiaries will pay almost the same premium for prescription drugs next year as they did this year.
Part D is the Michael Phelps of healthcare reform – providing victories today and a policy roadmap towards real healthcare evolution.
Premiums for drug plans that accompany basic Medicare coverage for the elderly and disabled will be an average of $30 in 2013, the department said today in a statement. The estimate is based on bids from private insurers who offer the plans to Medicare patients.
Smart partnership between government and the free market worksSATURDAY, AUGUST 4, 2012
Why I've Always Written So Much With Such Intensity And why I won't stop now.
By Barry Rubin
Nothing is stranger than having a normal life and then within a few hours knowing that it might end at almost any moment. That’s what happened to me when I was just diagnosed with what is called inoperable lung cancer. I am still waiting final results of the tests and the choice of therapies.
I have no desire to make this my focus but it’s been suggested that I write something about it that might be of broader interest.
First, for those of us whose understanding of cancer is based on past information, it is very important to understand that a lot has changed. That diagnosis twenty or thirty years ago would have given a person only a few months to live. Today, with many of the new therapies invented, one has a fighting chance. Still, it is tough to have your life expectancy lowered from around twenty years to a minimum of two within moments.
People always asked me why I wrote so much and so intensively. I never told them one of the real reasons: I always expected my life would be limited. My grandfathers died, respectively, at 42 and 44, both of things that could have been cured today. My father died of a heart attack at 62, and his life probably could have been extended many years today by all the new tests and drugs available. But I felt that once I passed that birthday, less than a year ago, I might be living on borrowed time.
They say that when you are fighting cancer that becomes a full-time job in itself. Supported by my truly wonderful family, I’m working on it. Right away one starts paring things down: unsubscribing to lots of things; knowing that I will never again have time for hobbies. The decision to start reading a book is like a major life choice.
And I know I won’t be going canoeing down the Jordan River with an old friend in August. In fact, having passed out briefly about a half-dozen times—though we think we’ve solved that problem—I’ll probably never drive again nor, after cancelling two trips, travel internationally. In fact, the way things are going at the moment, I might never eat solid food again.
The best thing to do is to accept everything calmly—bargaining, hysteria, rage, won’t do any good--and then decide that one is going to fight with the object of beating the disease. Unlike much of political life, this is not caused by malevolent forces.
This is not, however, the only transformative event I’ve had this week. I don’t want this to come out wrong but I have been touched and encouraged by an outpouring of emails from friends, acquaintances, and readers about how much they appreciated my work. Up until now, I’ve really thought that my articles have gone into a void.
As you know, we live in an era where many ideas, much truth, and certainly the kind of things that I think are largely barred from the most prestigious (although daily less so) media and institutions. We are either ignored or vilified. Now, though, the counter-audience has grown so long and people are so hungry for accuracy and cutting through the nonsense that our ranks have grown into the millions. When someone tells you that you’ve helped them, informed them, encouraged them, or even changed their lives it is an immeasurable feeling.
And while I wouldn’t go so far as to say that the cost has been worth receiving these messages, it is closer than one might ever believe.
There are some constructs I’ve come up with that I find comforting. Briefly:
Every living thing that has ever existed has died, at least in terms of being on this earth. If they could do it I can do it.
I feel like I have been captured by an enemy force (you all can insert specific names) and they want to execute me. I hope to escape or to be rescued by my friends.
Even if I didn’t have this disease, I could leave life on any day due to many causes without warning.
For 2000 years my ancestors dreamed of returning to their homeland and reestablishing their sovereignty. I have had the privilege of living that dream. How amazing is that?
We have to judge ourselves by whether we’ve lived up to our ideals and done our best. Not by the accumulation of power, wealth or fame; not for failing to achieve the impossible.
A famous Jewish story about that is the tale of Rabbi Zosia who said that he did not expect God to berate him for not having been Moses—who he wasn’t—but for not having been Zosia.
To me, that means we must do the best to be ourselves while trying to make ourselves as good as possible. I’ve really tried to do that. I don’t have big regrets, nor bitterness, nor would I have done things very differently.
And I’ve discovered the brave community of those who are supporting and encouraging each other in the battle against this disease.
Finally, I find myself identifying with a poem by a Turkish writer named Ilhami Bekir that goes like this:
“Neither vineyards, nor gardens
Do I ask.
Nor horses, nor sheep.
Don't take my soul away,
O God!
I am curious.
I must see how this game ends!”
The game, of course, doesn’t end and I don’t expect to live to see utopia realized. But it would be nice to live long enough to see America and the world pass out from this current dreadful era, to see some restoration of sanity and reality, some kind of victory for goodness, some kind of restoration of intellectual standards, and a higher level of justice.
Some friends tell me they think we’ve turned the corner and that there’s real hope of beating the terrible forces that have messed up our societies and insulted our intelligence and tried to sully our reputations.
That’s something worth living for and fighting for. I hope to do it with you people as long as possible.
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.
