A key point in the debate over renewing the Prescription Drug Fee User Act, or PDUFA, has been the ability of the FDA to review drugs as quickly as possible. Along with the pharmaceutical industry, various members of Congress complain the agency moves too slowly. But a new study in The New England Journal of Medicine contradicts those assumptions and also questions whether the speed of the review process is justified as part of PDUFA reauthorization.

To wit, the study compared first and total regulatory review time among all novel therapeutic applications submitted to the FDA from 2001 to 2010. The upshot? The FDA was approximately two months faster than the other two key agencies – the European Medicines Agency and Health Canada – in issuing approvals. And the FDA was three months faster when examining a sub-sample of therapeutics that had been approved by all three agencies during this time period.

Another interesting point: among therapeutics that had been approved in both the US and Europe, 64 percent were approved for use in the US first. Among those approved in both the US and Canada, 86 percent were approved for use in the US first. As a result, the study authors contend that concerns the FDA has emphasized safety at the expense of efficient approvals is misplaced. PDUFDA, by the way, is up for renewal every five years.

“There are a lot of concerns that FDA has been slowing down, because in the last PDUFDA, safety was emphasized. And so there are concerns that safety is slowing things down,” says Joseph Ross, an assistant professor at the Yale University School of Medicine. “But there’s not a lot of data is out there. FDA issues reports on performance goals, but they’re hard to understand in context. By comparing speed with which FDA is reviewing applications with European and Canadian agencies, we have an ability to benchmark. They serve similar populations and are under similar pressures.

“I think this shows pretty clearly that FDA has not slowed down and is moving at about the exact same speed in this PDUFA period as in the last PDUFA period and, more than that, moving faster than other regulators. But what’s the right speed? I don’t know what that is or what’s right or wrong. FDA has to balance these things. But to me, I think the concerns are overstated.”

As for the numbers, the authors identified 510 applications for novel therapeutic agents, of which 225 were endorsed by the FDA, 186 by the EMA and 99 by Health Canada. Of these, 289 were unique agents. The median time the FDA took to complete a first review was 303 days, compared with 366 days by the EMA and 352 days by Health Canada. The median total review time was also shorter at the FDA. Among the 289 unique novel therapeutic agents, 190 were approved in both the US and Europe, of which 121, or almost 64 percent, were first approved by the FDA. Meanwhile, 154 were aproved by both the FDA and Health Canada, and 132, or nearly 86 percent, were first approved by the FDA (here is the abstract).

Drilling down, the FDA also outperformed the other agencies when reviewing two different therapeutic categories. For cardiovascular, diabetes and endocrine drugs, the FDA median review time was 305 days, compared with 356 for the EMA and 352 for Health Canada. The FDA trailed in total review, though, posting 365 days, compared with 356 for the EMA, although Health Canada posted 472 days.

For oncology meds, the FDA was fasted across the board. When comparing median time, the FDA took 237 days, while the EMA used 384 days and Health Canada needed 345 days. The FDA total time was 264 days, compared with 382 for the EMA and 354 for Health Canada. There were similar contrasts for respiratory and gastrointestinal drugs: median FDA time was 308 days versus 362 for the EMA and 345 days for Health Canada. Total FDA review time was 335 days compared with 362 for EMA and 345 for Health Canada.

Findings were mixed, however, for other categories. For anti-infectives, median FDA time was 275 days versus 348 days for EMA and 245 days for Health Canada. Total FDA review time was 284 days, while EMA took 348 days and Health Canada needed just 245 days. For musculoskeletal and pain drugs, median FDA time was 369 days, while EMA needed 399 days and Health Canada took 411 days. Total FDA time was 431 days versus 399 for the EMA and 478 for Health Canada.

For psychiatric and central nervous system drugs, median FDA review time was 335 days compared with 413 for the EMA and 404 for Health Canada. Total FDA time was 463 days compared with 413 for the EMA and 514 for Health Canada. For all other drugs, the median FDA review time was 303 days versus 345 days for the EMA and 378 for Health Canada. Total FDA review time was 349 days, while the EMA needed 345 days and Health Canada used 402 days.

Ross also pointed out that the study also debunks the notion that drugmakers should seek approval elsewhere first, since he and his colleagues were able to document that, for meds approved in Europe and the US, the available median time was about three months faster in the US. In other words, drugmakers “seem to be going to the agencies at the same time, but their drugs end up becoming available first in the US,” he says.

Some numbers: among 289 unique novel therapeutic agents, 190 were approved in both the US and Europe, 154 in both the US and Canada, and 137 in both Europe and Canada. Among meds approved in both the US and Europe, 64 percent were first approved in the US, with the drugs available a median of 96 days earlier in the US. Similarly, among drugs approved in the US and Canada, 86 percent were first approved in the US, and median availability was 355 days earlier in the US.

Three years ago, a former Bristol-Myers Squibb senior vice president named Andrew Bodnar pleaded guilty to lying to federal authorities about a botched patent deal involving the Plavix blood thinner, an episode that contributed to an overhaul of its c-suite. As for Bodnar, a judge did something highly unusual that quickly became a wry joke – instead of throwing the book at him, he ordered Bodnar to write a book so others might learn from his alleged mistakes.

Now, the book is out…sort of. A 253-page manuscript, which was entitled ‘The First Question,’ was filed in federal court last October as part of the deal (which also included a $5,000 fine). Although his memoir may not be considered a page turner (he is no Keith Richards), Bodnar does provide some useful insights into some of the behind-the-scenes workings of the pharmaceutical industry. And he mostly does so in a confessional tone.

“He ordered me to tell my story. To write a cautionary tale. To tell others how to avoid the Gehenom (which is Hebrew and roughly means netherworld) in which I have found myself for the past five years. Thankfully, for everyone other than me, this hell is so particular, that no judge’s order could ever generalize it. And, yet, by order of the court, I must write the story. And so I have,” Bodnar writes.

The tale begins when Bodnar is traveling and receives an urgent phone call from a lawyer at Cravath, Swaine and Moore that the FBI has raided his office – and the office of Peter Dolan, who was the Bristol-Myers ceo at the time. Chaos reigns but, as I will soon learn, this is as nothing compared to the vacuum that is about to suck the air from my every breath for years to come,” he writes.

After deciding that he would not begin the book by urging readers to ‘call me schlemiel,’ the 64-year-old Bodnar proceeds to tell his version of events. The feds say he lied to the Federal Trade Commission about the arrangement between Bristol and its Plavix marketing partner, Sanofi, to keep Apotex from launching a generic version of Plavix. Bodnar writes the feds clung to a “mistaken belief that I had made a statement to the government that I knew to be false.”

Much of his recounting is inside baseball, but offers interesting glimpses into the approach taken toward generic competition and, particularly, dealings with Apotex. There is also a lot of detail concerning the government investigation and subsequent haggling over events, especially those that will determine his fate. There are also sections that review his uncomfortable dealings with New Jersey Gov. Chris Christie, who was the US Attorney at the time.

But the often-dry story is interspersed with sweet memories of his childhood and family life, which are told in third person. Notably, Bodnar recounts how his mother survived the Holocaust, the escape from Communist Hungary as the Soviets invaded in 1956 and the life of an immigrant family in the United States during an era when prosperity and achievement seemed always in reach.

Although his mother, Magda, developed Alzheimer’s, Bodnar imagines she would have told him that ” ‘at least they had to go to a judge to get a search warrant,’ continuing to make the argument she never stopped making for the ‘Land of the Free’ to which she had, at great peril and to her own well being, brought her son,” he writes. She passed shortly before he was indicted.

We asked his attorney about publication for the public, but have not heard back. We will update you accordingly. Meanwhile, if you have some free time, you can read ‘The First Question’ right here. [UPDATE: One of his attorneys wrote us to say that they "have nothing more to say about Dr. Bodnar...As you can imagine, Dr. Bodnar has moved on and does not wish to re-visit a painful part of his life.]

Hat tip to The Wall Street Journal, which first reported the appearance of the book in the court system.

As the FDA continues to grapple with devising a final blueprint for developing biosimilars, big drugmakers and biotechs are jockeying for position. A decision, however, is not due for some time. Still, the law that allows biosimilars on the marketplace is two years old and the FDA has yet to receive an application. The implications, of course, will be enormous on the US health system, given the high cost of biologics and the potential for altering the cost of treatment for assorted diseases. We asked Gillian Woollett, a vice president at Avalere Health, a healthcare consulting firm, for an update on where the issue may be headed…

We have ‘Moore’s Law’ of Biotech. With nearly 30 years of experience in the science enabling the creation and manufacture of biologics, the possibilities for these products continue to expand exponentially. To date, there have been 149 approvals by the FDA for the marketing of a recombinant biologic in the US and many more classic naturally-sourced biologics, such as vaccines and blood products, continue to serve major health needs. We have over 900 in clinical development. Currently, each biologic is single sourced and these valuable products are premium priced for good reason – they save and change lives. However, they also cost on average $22 a day versus brand drugs at around $2 a day and small molecule generics that cost just cents.

Establishing a US Market. A confluence of factors has led to the creation of a market for biosimilars, but the main driver is the clear success of the originator products, totaling some $100 billion in annual sales in 2010 and expected to reach $150 billion by 2016. Indeed, by 2016, seven of the top 10 pharmaceuticals worldwide will be biologics. Over the three decades, recombinant biologics have become ingrained in our clinical armamentarium to prevent, manage and treat conditions from infectious diseases to cancer. And now, a slew of patents for the leading biologics are expiring, creating the immediate and obvious question as to what will be the nature of the competition?

A wide range of stakeholders, from payers to patients, are encouraging the FDA to implement the new regulatory pathways mandated by the Affordable Care Act, a pathway largely enacted based on the expectation of significant savings. FDA can encourage biologics sponsors to make and submit for approval similar products, hence their name biosimilars, that serve the same market need and compete with the original biologic, but ultimately it is up to the sponsors to actually submit applications. The implementation of this pathway, as well as policies that allow patient access, are the key ingredients to produce cost-effective, high-quality, safe, pure and potent biosimilars that can enable a wider range of treatment choices for patients and their physicians. But to date, FDA has received no biosimilar applications.

Success in Europe Creates Pressure in the US. Europe approved their first biosimilar in 2006, two years after the new directive was enacted, and they now have 14 biosimilars approved for Somatropin, Epoetin alfa and Filgrastim. While initially slow, the uptake for these products has expanded, and in some countries, the biosimilars now outsell the originator by quantity – for example, filgrastim in Sweden. And in other countries, they have changed the practice of medicine through affordability enabling access – for example, filgrastim in the UK. And there have been no reported problems with quality, safety or efficacy for any marketed biosimilars.

When a biosimilar is approved in Europe it gets approved centrally, but the European Medicines Agency is silent on interchangeability of the biosimilar with its originator reference product (FDA does have the authority to designate biosimilars as interchangeable, meaning that they are substitutable without the involvement of the original prescriber). The European regulatory approach is built on a regulatory concept created by the FDA that is called comparability, which enables manufacturing changes to be made to already-approved biologics without requiring complete redevelopment. However, while biologics pre- and post-manufacturing change are fully-interchangeable, Europe leaves interchangeability/substitution up to the health authorities in each member state. In some ways, this is not that different from how the FDA licenses centrally and then each state in the US has its own rules on the practice of medicine/pharmacy, including substitution.

Europe and Changing Costs. The use of the biosimilar and how it is ‘preferred,’ or not relative to its reference product, is the decision of each of the individual health authorities in each of the 27 countries that comprise the European Union. This is where it gets interesting, and this is where we can learn the most about incentives and what changes medical practice. Some countries in Europe use tenders and companies compete on price (like US generic drugs), while others use various levels of central control. Savings have varied tremendously. Some health authorities have reportedly achieved savings with some products of over 75 percent. In other instances, 30 percent to 50 percent have become more routine. More products do lead to greater competition and even originator products have shown reductions in price to defend market share, such as in Germany with the erythropoeisis stimulating agents, where even second and third generation products cut their prices when biosimilars to the first generation became available.

The Price of Market Access Matters. Europe has gained confidence through its approval of successful biosimilars and the US can learn from this, but the big question is whether these biosimilars from other highly-regulated markets will be the able to access the US market or if biosimilars will be able to compete here at all. For instance, it is not yet clear whether global development for biosimilars will be possible in the manner that we have come to expect for originator products. No one has yet filed an application for a biosimilar in the US, and we are now over two years after enactment of the law here. FDA is advocating what the agency is calling a “more scientific” approach than EU, and has three draft guidances out for discussion, an imminent public meeting and more guidances proposed. Stakeholders are responding along expected lines, but the for and against biosimilar poles are perhaps softening. One concern is that the addition of more science by FDA adds to cost of the ultimate products, and does not change the products in and of themselves, hence adds little value for patients.

Payers and Their Policies. If biosimilars are approved in the US, how will the payers react? Initially, there were expectations that they would be treated like generic drugs, and the competition would be about price. More recently, with the cost of development now estimated at up to $250 million for each biosimilar, the indication that detailing will be required, and that FDA is not ready to use their interchangeable authority, means that biosimilars are increasingly looking more like branded products. However, the best of both worlds is still possible. If markets can expand, with no compromise in quality, safety or efficacy, biosimilars may allow the practice of medicine to change through affordability.

For instance, in the UK, the use of filgrastim prophylactically (and according to UK and US treatment guidelines) rather than just as a treatment when febrile neutropenia occurs after chemotherapy, became possible through biosimilar availability and affordability. This illustrates how markets are rarely saturated when individual and collective costs are high. However, in the US we have many payers, and each may see the opportunities differently. Already, activities in different US states suggest that even public payers may differ in their enthusiasm to use biosimilars to help manage health care costs.

Decisions Today And Choices Tomorrow. As I mentioned earlier, biologics will account for more than half of the Top 10 selling drugs by 2016. These next few years will also bring a large number of patent expirations to the pharmaceutical industry, making many companies strategize around how to best to compete head-to-head with one another in negotiating their share of the market space. Incentives can work in interesting ways, but ultimately these are multi-billion dollar markets for an industry collectively facing challenges with their approvals of originator products. There will be competition, but as we get there all stakeholders need to consider the results of their demands carefully, and both for the short terms consequences and the longer term impacts.

In the end, the market for biosimilars will depend on the costs and who pays, and implicit in that who makes the decisions. And even if the new pathway included in provisions under the Biologics Price Competition and Innovation Act (BPCIA) is overturned by the Supreme Court or not chosen for other reasons, competition will still exist and decisions will need to be met in order to negotiate access to large and expanding markets for biologics. Whatever we call the products, ultimately patients need access to therapies and access is often a matter of life and death.

Two years ago, nearly two dozen medical journal editors and pharma execs convened a roundtable to grapple with growing controversy about the credibility of published research. Specifically, they were sorting out complaints concerning ghostwriting (see here), the extent to which researchers are given full access to clinical trial data and perceptions that industry-sponsored research can be tainted, among other things.

Now, they have published a list of 10 recommendations, which appeared last week in Mayo Clinic Proceedings, and the participants in the so-called Medical Publishing Insights and Practices initiative hope to “elevate trust, transparency and integrity.” Although there is nothing mandatory about the output – these are 10 recommendations, not 10 commandments – the MIPP urges drug and device makers to “ensure uniform adoption.”

So what do they recommend? All trial results, favorable or unfavorable, should be made public on a timely basis; improve understanding and disclosure of potential researcher conflicts; improve disclosure of authorship contributions and writing assistance and look to end ghostwriting and guest authorship; report adverse event data more transparently; provide access to more complete protocol info; transparently report statistical methods used in analysis; ensure authors can access complete study data and support sharing prior reviews from other journals (here is the complete list with conflict disclosures).

“All parties should take the opportunity to extend these efforts toward raising the standards for all research activities, irrespective of industry sponsorship. Such efforts are vital to closing the credibility gap in reporting industry-sponsored clinical research,” concludes he MIPP, which is funded by Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Merck, Pfizer, and Takeda Pharmaceuticals North America.

Overall, the move is applauded for being undertaken, but a pair of Yale University School of Medicine professors, who have regularly advocated for greater dissemination of clinical trial results (read this), say the recommendations do not go far enough and, moreover, lack any enforcement mechanisms that could ensure journals and companies implement them.

“It’s great to have principles articulated, but I wonder about accountability and enforcement – how will we know if the promulgation of these principles actually improves the quality of the research? I am concerned that the only thing that will truly bridge the gap is the availability of data, so that the reproducibility of the science – and its quality – can be directly assessed by external scientists,” Yale’s Harlan Krumholz writes us in an e-mail. “Nevertheless, many of these recommendations are likely to improve the current situation.”

His colleague, Joseph Ross, adds this: “I have no problem with the recommendations they have made, but these simply represent good clinical trial research practice. That they are recommending that clinical studies address important questions and that all results be published is absurd. To me, it is clearly unethical not to do these things. If anything, these recommendations merely confirm our strong skepticism of the industry-funded clinical trial universe, as they imply that the unethical practices these recommendations address are just as widespread as we believed.”

Another academic who has chastised journals and industry over research disclosures, Joel Lexchin, a professor of health policy at York University in Toronto, believes the recommendations are filled with “should and could,” and complains that some are “weak.” As an example, he writes us that the recommendation on data disclosure “does not actually require companies to allow authors to have unrestricted access to all data. It merely states that companies should make their policies on data disclosure clear to authors.”

He notes that drugmakers are not asked to submit full protocols along with manuscripts and journals are not required to publish protocols. “The recommendations just ask journals to make their policies on protocols clear,” he continues. Journal editors are not recommended to disclose conflicts, he continues, nor is there mention of publishing companies and drugmakers establishing false journals, as Elsevier did for Merck in Australia.

He adds that meta-analysis have found research sponsored by drugmakers is more likely to show positive results than research supported by other funding. “This current set of recommendations, in my opinion, will not eliminate this relationship between funding and results,” he writes (we should note that Lexchin provided the same comments to Medscape, which first reported the recommendations).

Good morning, everyone, and how are you today? Tis the middle of the week and that means a cup or three of stimulation is in order. Please feel free to join us. This will be another busy day as we go out of our way to forage for documents and attempt to contact the uncontactable (this is not really a word, but we enjoy the imagery). We trust you will be equally busy, so here are a few tidbits to get you started. Hope your day goes well and drop us a note if you come across anything interesting…

Court To Review Appeal of PA Risperdal Dismissal (Philadelphia Inquirer)

Piramal To Buy Decision Resources For $635 Million (Hindu Business Line)

UK’s NICE Backs J&J Zytiga Prostate Cancer Med (Dow Jones)

The Run-Up To The ASCO Meeting (Dow Jones)

Eight Drugs To Watch At ASCO (Xconomy)

UK’S NICE Delays Drugs For Years: Report (Daily Mail)

Family With Alzheimer’s Gene Gets Roche Drug In Trial (San Francisco Chronicle)

Pfizer Cuts 50 Jobs At Estrogen Facility (Alberta Farm Express)

MSF Calls Global Vaccine Plan Flawed (Pharma Times)

BASi Plans More Cost Cutting (Outsourcing Pharma)

Pfizer Torisel Cancer Trial Failed To Best Bayer Drug (Pharma Times)

FDA Clears New Bristol-Myers Plant (Associated Press)

EDITOR’S NOTE: Please check this post for updates

morning coffee pic thx to chichacha on flickr

Last week, the American Psychiatric Association unexpectedly backed down from two controversial proposals that would have increased the number of people who could have been diagnosed with psychotic or depressive disorders. The change meant that attenuated psychosis syndrome and mixed anxiety depressive disorder will not be listed in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, or DSM, to be published next year.

The move was greeted with applause by critics who more often accuse the organization of wantonly adding to the list of psychiatric diagnoses that may greatly increase the number of people considered mentally ill and, therefore, eligible for psychiatric and medical treatment. The DSM, which is known as the Bible of psychiatry, is officially a reference tool, although its outsized influence stokes concerns that many psychiatrists rely too heavily on its diagnoses for guidance.

The DSM “has become the arbiter of who is ill and who is not, and often the primary determinant of treatment decisions, insurance eligibility, disability payments and who gets special school services,” Allen Frances, a former psychiatry department chair at Duke University School of Medicine who led the DSM-4 task force, wrote in The New York Times. “DSM drives the direction of research and the approval of new drugs. It is widely used (and misused) in the courts.”

Assembling the upcoming DSM-V has, meanwhile, spawned enormous controversy. For instance, the definition of addiction is being revised to include gambling and may also introduce a more general diagnosis called “behavioral addiction — not otherwise specified.” The APA maintains such moves can save health care dollars down the road, but critics say resources may be used unnecessarily to treat substance abusers who are classified as addicts.

There has also been debate about Premenstrual Dysphoric Disorder, or PMDD, and whether the affliction should be updated as a full-blown problem alongside the likes of Major Depressive Disorder or remain a diagnosis in need of further study. The head of the APA task force, which will make a recommendation, insists PMDD is a legitimate health problem and evidence exists to warrant a diagnosis (read more here).

A backdrop to the DSM-V controversy are ties between members of the various APA working groups and drugmakers, which would benefit if new diagnoses are listed or definitions expanded in ways that more medications would be prescribed. A recent paper in PLoS Medicine noted that 69 percent of the DSM-5 task force members have ties to drugmakers, which is up from 57 percent of the DSM-IV task force members (see here).

Frances disagrees. “Many critics assume, unfairly, that DSM-V is shilling for drug companies. This is not true. The mistakes are rather the result of an intellectual conflict of interest; experts always overvalue their pet area and want to expand its purview, until the point that everyday problems come to be mislabeled as mental disorders, he wrote. “Arrogance, secretiveness, passive governance and administrative disorganization have also played a role.”

This point is likely to remain a debate within a debate. Nonetheless, the wider issue remains in play. And Frances proposes that a federal agency ought to assume the job of developing the DSM, although he believes a new organization would be required, one that could be housed in the US Department of Health and Human Services, if not the Institute of Medicine or the World Health Organization. An equivalent of the FDA is needed to “mind the store,” as he puts it.

This may raise a different set of objections, of course. To what extent, for instance, should a federal agency delve deeply into determining diagnoses and definitions? On the other hand, perhaps this would remove the concerns over self-interest and conflict that have tainted the process. What do you think?

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An FDA panel may have recommended a new Pfizer pill for rheumatoid arthritis last week, but of course, the drugmaker must still win over regulators, doctors and payers. And while Wall Street is betting the FDA will approve tofacitinib, convincing payers of its worth may prove more difficult. Although pricing will be a major determinant in coverage, it is clearly not the only factor.

How so? A new survey finds that nearly 39 percent of managed care entities will require patients to first fail at least two other treatments – such as the Humira or Enbrel anti-TNF inhibitors – before providing coverage. But only 27 percent held the same view before the FDA advisory committee met last week. Why? The FDA panel noted it was not possible to make conclusions about the effect of tofacitinib on the progression of structural damage in RA.

This particular point had an impact on payers. Unfavorable impressions of the pill rocketed from 0 – as in zero – to 39 percent, and favorable impressions among payers plunged to just 8 percent from 54 percent. Meanwhile, neutral impressions held by payers increased to 54 percent from 46 percent before the panel, according to Reimbursement Intelligence, a market research firm that queried 30 large payers after the FDA advisory panel on tofacitinib was held.

“Clearly, payers have some concerns,” Rhonda Greenapple, who heads the market research firm, tells us. “After reviewing the panel recommendations, a substantial number of payers changed their responses when we asked them how they thought their plan would manage access to tofacitinib… The question is do they view it as equal or not equal to the anti-TNF inhibitors, and I interpret this to mean that most do not. This means it will be a third or fourth line treatment.”

In general, almost 42 percent of payers viewed tofacitinib safety as neutral and 43 percent had the same take on efficacy. As a result, Greenapple says that payers believe the Pfizer pill will have only 6 percent market share six months after becoming available and that will rise to 13 percent after one year. And so, she adds, tofacitinib will have the same share as the Remicade treatment sold by Johnson & Johnson.

The survey also found that 71 percent of payers would require prior authorization, and 42 percent would require patients to fail on methotroxate, which is widely used as a first-line treatment, before covering the Pfizer pill. At the same time, nearly 39 percent would require patients to first try and fail treatment with at least one anti-TNF inhibitor. The numbers exceed 100 percent because managed care can demand prior authorization and other requirements.

All of this suggests that pricing will play an important role in how tofacitinib actually fares with managed care. Pfizer has not discussed its pricing strategy, but Wall Street increasingly expects the drugmaker to offer discounts compared with anti-TNF inhibitors – notably, Humira, which is sold by Abbott Laboratories – in order to gain the best possible positioning on formularies.

EDITOR’S NOTE: An earlier version of this post described tofacitinib as a biologic. The drug is is part of a new class known as JAK inhibitors, which are small-molecule medications.

As Novartis gears up for an important court case in India that can be traced to the pricing and accessibility of its Gleevec cancer med, the drugmaker is now facing a grassroots challenge in the US over the same issue. A petition was recently created on Change.org to demand that Novartis lower the price and that Congress should intervene if the drugmaker fails to do so voluntarily.

“Novartis developed this drug in the 1990s. In the years since then, the price of the drug has increased astronomically. Novartis must have paid their research costs long ago, but the price just keeps rising. Patients with CML leukemia are dependent on the drug to keep them alive. Our US representatives should work with FDA to pressure Novartis to reduce the cost of Gleevec,” the petition states. As of today, more than 300 people have signed (see here).

The petition is “notable as a reflection of the growing economic desperation here,” writes Joana Ramos, an independent health policy consultant in Seattle. “The already-high, formerly global price has climbed sharply upward in recent years, and coincides with privately insured patients being now forced to shoulder much more of the cost themselves, increasingly impossible for so many. (An) informal survey shows the retail price of an average monthly (supply) of 400mg tablets seems to now be in the $6,000 to $7,500 range” (look here for one example).

Debate over Gleevec pricing has long plagued Novartis, which initially charged about $2,400 a month when the medication was launched in 2001. Five years ago, Brian Druker, who was the key researcher behind the discovery of the drug and who heads the Knight Cancer Institute at Oregon Health and Science University, caused a stir when he publicly chastised Novartis for pricing that caused him “considerable discomfort” (see here).

“Pharmaceutical companies that have invested in the development of medicines should achieve a return on their investments. But this does not mean the abuse of these exclusive rights by excessive prices and seeking patents over minor changes to extend monopoly prices. This goes against the spirit of the patent system and is not justified given the vital investments made by the public sector over decades that make the discovery of these medicines possible,” he wrote in an essay at the time.

The issue has been most prominently on display in India, where the Supreme Court will hear arguments this summer over whether the government had the right to deny a patent to Novartis for the cancer med. The drugmaker wants a patent based on a new form of its drug, which would offer a 20-year extension. A previous government ruling denied its request after deciding the new form did not meet a standard for enhanced efficacy. Patient advocates argue that a Novartis victory would amount to evergreening, a reference to patent extensions based on minor changes, and inhibit access since generic drugmakers would be prevented from making lower-cost versions (see this).

We asked Novartis about the petition and received this reply from a spokesman: “Novartis seeks to provide treatment options at prices which reflect the value they bring to patients and society, the scientific innovation they represent and the necessary investment in clinical studies to support development of innovative medicines.” He added that the drugmaker runs patient assistance program that provided $144 million of free Gleevec to 4,000 people in the US last year.

The Gleevec patent, by the way, will expire in 2015 in the US.

pill pic thx to anolobb on flickr

Hat tip to Healthwatched

Hello, everyone, and how are you today? A spot of rain has descended on the Pharmalot corporate campus, where we have successfully hustled the short people off to their schoolhouses. And not a moment too soon, either, since we have another busy day filled with reading documents, phoning people and, hopefully, learning some interesting tidbits. We know you can relate, so here a few items to get you started. We hope your day goes well and that you accomplish much. See you soon…

Cardinal Facility Banned From Shipping Controlled Substances (Associated Press)

US Launches Ambitious Plan To Research Alzheimer’s Treatments (Reuters)

Who Isn’t Looking At Amylin? (Bloomberg News)

Achillion Gets FDA Fast Track For Hepatitis C Drug (Reuters)

J&J Returns Impotence Pill Rights To Furiex (Reuters)

A Personalised Vaccine For Fighting Brain Tumors (London Evening Standard)

AstraZeneca Anti-Trust Fine Should Stand: EU Court Aide (Bloomberg News)

Merck KGgA Committed To Big Cost Cutting As Profits Fall (Pharma Times)

UK Lawmakers Urge Action On Drug Shortages (Reuters)

Hospira Recalls Pain Drug Cartridges On Overfill Concerns (Dow Jones)

AstraZeneca Cuts 400 Jobs In Sweden (The Local)

SNBL Claims To Have Fixed Troubled Facility (Outsourcing Pharma)

EDITOR’S NOTE: Please check this post for updates

rain pic thx to sterlic on flickr

As their European counterparts did last month, the FDA has recommended continued use of the Gilenya multiple sclerosis pill sold by Novartis, but did say the drug should carry stronger warnings about heart risks and that some patients should undergo increased monitoring. The move was largely expected after the European Medicines Agency issued a similar alert, despite arguments by a non-profit safety watchdog that further restrictions are needed.

Although cardiovascular risks were known at the time of approval two years ago, the regulatory review was undertaken in response to patient deaths, including an unexplained sudden death of one person within 24 hours after taking Gilenya for the first time (back story). The back-to-back regulatory decisions will likely ease investor concerns over the prospects for the pill, which Novartis continues to hope will generate blockbuster sales.

The drugmaker has been counting on Gilenya to help compensate for the loss of patent protection on such big-selling drugs as the Diovan blood pressure pill. Meanwhile, competition in the MS market looms as Biogen Idec plans to seek FDA approval for an oral pill shortly. Last month, Novartis execs maintained that between just 4 percent and 7 percent of MS patients may be at risk for the sort of cardiovascular issues that prompted the FDA and EMA reviews.

The FDA advised doctors not to prescribe Gilenya to patients with a history of cardiovascular and cerebrovascular disease or those on heart-rate lowering meds. If Gilenya is considered needed, heart rates should be monitored at least overnight following the first dose. But all patients should have an electrocardiogram and blood pressure measured before a first dose and for six hours after treatment. And continuous ECG monitoring is recommended.

In reaching its decision, the FDA noted data show the maximum heart rate lowering effect usually occurs within six hours of the first dose, but the maximum effect may occur as late as 20 hours after the first dose in some patients (read the FDA statement and data summary here and the EMA report here). Despite these warnings, the FDA did not suggest that all Gilenya patients should be monitored overnight, which Wall Street viewed as a worst-case scenario because such a step would likely have inhibited more widespread usage.

Last month, the Institute for Safe Medicine Practices called on the agency to substantially restrict Gilenya usage and enhance patient monitoring after reviewing adverse events that were reported to the FDA during the second quarter of 2011, shortly after the drug was approved. The watchdog group also criticized the agency for placing Gilenya in its fast-track approval process (read here).