Latest Drugwonks' Blog

You can call me ALS

  • 04.24.2015
You mean it really isn't always the FDA's fault?

According to a report in FierceBiotech …

The Wall Street Journal has caught up with the Genervon controversy, recapping a series of events from the last few days that followed the big social media campaign to gain an instant approval for a new ALS drug based on the results of a 12-patient study. FierceBiotech readers will know already that the data for GM604 were questioned by Steve Perrin, president and chief scientific officer of the ALS Therapy Development Institute, and that the FDA followed up a day later with an extraordinary challenge to Genervon to publish the data on a drug that the biotech has touted as a major advance for patients.

The Journal, though, did manage to nail down an answer from the company, run by Winston Ko, about the application the patient community believes has been filed for accelerated approval.

There isn't one.

Genervon tends to prefer email communications these days. And the company told the Journal that it is "at the point of communicating with FDA about whether [the agency] would accept our formal application" for accelerated approval.

Genervon, meanwhile, has already repeated claims to us that it made a "formal request" for accelerated approval, an assertion that dates back at least to last month. The company has stated in releases that it has "met with the FDA and has submitted an Accelerated Approval application." The biotech has also claimed several times that an accelerated approval decision was already in the works at the FDA, and it's done nothing to stop publications like The Washington Post from reporting that an application is at the FDA as it repeatedly prodded dying patients and their families to back calls for a quick approval as their only chance of getting the drug and staying alive.

Back in mid-February, Genervon issued a statement saying that it had met with the FDA and asked for accelerated approval three times during the course of the get-together, then asserted that the agency had 30 to 60 days to respond. That mid-April deadline--which has been repeated by the petition's sponsors--helped trigger a frenzy of petition signing at, which currently has more than 535,000 signatures backing instant approval.

But that's not going to happen, because without an actual application, there is no 60-day response time for the agency to accept or reject the application for review. Given the FDA's challenge to Genervon, and its clear doubts about the data from the tiny study, the company's chances of being received at a wary FDA with open arms lies somewhere between none and zero.

As far as making any public statements about Genervon, though, the agency's hands are tied by federal law.

Patients and their families should know that there is no decision pending at the FDA. They might also ask themselves if Winston Ko and Genervon have been stirring false hope among the dying in an attempt to create a social media campaign that would push the FDA to sanction the drug's sale on questionable data.


It looks like the FDA (and specifically John Jenkins) has had enough and isn't going to take it anymore.

From the pages of Medical Marketing & Media …

FDA takes unusual stance on ALS drug

The FDA said Genervon should supply more data if it wants an accelerated approval.

The FDA took an unusual public stand Friday when it publicly asked Genervon Biopharmaceuticals to release all data from the California drugmaker's recently completed trial for an experimental drug for amyotrophic lateral sclerosis, a neurodegenerative disease also referred to as ALS and Lou Gehrig's disease.

Doing this would allow a more informed discussion of the trial findings among ALS stakeholders for GM604, the FDA said.

“It is certainly not a routine practice,” FDA spokesperson Sandy Walsh told MM&M.

The FDA's request follows a surge of patient activism, including a petition that is urging the FDA to grant an accelerated approval to the drug based on a Phase-IIa study comprising 12 patients. An accelerated approval would allow the drug to be distributed as is to the general patient population as opposed to using pathways like the FDA's compassionate use provision, which grants patient-by-patient access to unapproved investigational drugs.

The FDA has a history of taking patient lobbying efforts into consideration, such as when it approved Sanofi's Lemtrada for multiple sclerosis.

Steven Perrin, CEO of the ALS Therapy Development Institute, which conducts ALS research, highlighted what he considers problems with the research on his blog. He told MM&M that the data set is far too small for a regulatory decision for reasons that include the size of the clinical trial and because ALS progression differs patient by patient. He said this makes it difficult to back efficacy claims.

Perrin said putting ALS patients on a drug lacking sufficient data could jeopardize other experimental drugs that do have Phase-III data because patients taking GM604 would not be able to take another candidate, be it one that his group supports or one that is backed by another company.

Perrin said he doesn't want to kill the drug but he does want Genervon to “do the right thing” and adhere to traditional regulatory protocols and run a larger clinical trial.

Perrin is not Genervon's only critic. The Washington Post reported earlier this month that one of the researchers involved in the study said more data was needed.

Genervon said in press releases that finding a treatment for the disease requires an unconventional approach. Genervon declined to provide answers to queries including if the company plans to pursue late-stage clinical trials and if it has provided the FDA with all of the information it has on hand. Chief Operating Officer Dorothy Ko referred MM&M to its website.

Genervon said in an April 13 press release that pursuing an accelerated approval has some risks because it would mean exposing this early-stage treatment to “a full spectrum of heterogeneous ALS patients,” rather than if the drug went through traditional testing, which the company described as “a more secure and conservative approach.” Genervon also said drug sales from an accelerated approval would allow the company to fund further development.

The FDA noted in its public request that it is not allowed to release clinical trial data about experimental medications, but the drugmaker can.

Perrin acknowledged that it is easy to understand the appeal of an experimental medication but that choosing a drug that is not scientifically supported can prevent patients from trying one that has more verifiable outcomes. “They are desperate for hope and they want access to stuff, even if there is not a lot of data,” he said.

Genervon told MM&M it is reviewing the FDA's request.

What happened to keeping politics away from science?

Some fine legislators in the World’s Greatest Deliberative Body -- Senators Joe Manchin (D/WVA), David Vitter (R/LA), Shelly Moore Capito (R/WVA) and Tim Kaine (D/VA.) -- have just introduced the so-called FDA Accountability for Public Safety Act. So-called, because these fine legislators do not seem to understand that there is no such thing as a drug that is 100% safe.

Among other items, the legislation would require the FDA to hold advisory committee meetings for all opioids under review and submit a report to Congressional committees explaining why the agency approved an opioid against an advisory committee's vote, including scientific evidence related to patient safety.

Note to fine legislators –“safety” is a relative concept viewed through the perspective of benefit/risk.

The bill also would force FDA to publicly justify its approval of any opioid drugs not recommended by advisory committees for safety reasons. Note to fine legislators – all drugs have risks. Products are not abused because they are “unsafe.”

Many raise the FDA adcomm vote on Zohydro as an example of the agency acting to approve an opioid after a negative committee vote. The soundbite you’ve likely heard is that the vote was against approval of the drug. That’s true. What you probably don’t know is that, by a vote of 11-2, the experts affirmed that there was no evidence to suggest Zohydro had greater abuse or addiction potential than any other opioid.

Note to fine legislators – facts are stubborn things.

The bill also stipulates that the FDA commissioner make a final decision regarding approval of opioids not recommended by the committees due to safety concerns. Note to fine legislators – all approvals are done under the name of the Commissioner – and then testify before Congress if called upon. Really? Can you hear those political sabers rattling?

In addition, the agency would have to disclose any conflicts of interest that may be held by its officials. Do these fine legislators mean the members of advisory committees? If so, this already happens. If they mean FDA staff – then shame on these fine legislators for casting unfair and unfounded aspersions on overworked, underpaid, and deeply committed public health officials.

But wait, there’s more. A sponsor would be prohibited from distributing an approved opioid until FDA submits its report to Congress. After all, these fine legislators are all highly trained scientists capable of judging the issues of crucial importance to the tens of millions of American who suffer from chronic pain.

Perhaps these fine legislators should read the FDA’s “Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling” which explains the FDA’s current thinking about the studies that should be conducted to demonstrate that a given formulation has abuse-deterrent properties. It also makes recommendations about how those studies should be performed and evaluated, and discusses what labeling claims may be approved based on the results of those studies.

Besides being a bad idea for opioids – the FDA Accountability for Public Safety Act is a slippery slope towards political interference in the drug approval process. If the FDA must defend its approvals of opioids today, will it have to defend its decisions not to approve cancer drugs tomorrow? Should the agency have to explain its decisions to Congress when it approves a drug via an expedited approval pathway too?

Question to fine legislators: What’s next?

Pazdur Speaks!

  • 04.16.2015

Love him or hate him (and many people do both), Dr. Richard Pazdur -- director of the FDA's Office of Hematology and Oncology Products-- is the world's most important cancer drug regulator.

In an exclusive web interview, Dr. Pazdur tells  BioCentury why the agency is racing to approve new cancer drugs. He says new targeted drugs and immunotherapies with unprecedented efficacy are the payoff from 20 years of basic science. He calls for greater patient engagement in drug development, says compassionate access should be improved, and predicts rapid uptake of biosimilars.

The four-part interview contains the segments:

·      Cancer "Rocket Docket" – How the FDA is racing to approve new drugs because it is seeing unprecedented efficacy.

·      Patient Power. Why the patient voice is critical to improving cancer drugs.

·      Precision Medicine. How the agency is trying to make precision medicine a reality for cancer patients.

·      Compelling Case. The case for doing more to create better cancer drugs for kids.

The complete video interview can be found here.

Ever heard of the Precautionary Principle? It’s basic premise is that you shouldn’t do anything new until you know everything about how it works or what it’s impact will be. Not a good theory on paper – and even worse in practice. For example, if you believe in this concept, you wouldn’t allow any new life-saving medicines on the market before you knew everything about how it would impact patient lives.

When it comes to science, innovation involves a careful balancing of benefits and risks based on the best possible scientific information. And it should not come at the cost of doing harm to public health by slowing down the availability of new and better technologies.

Now consider the case of neonicotinoid pesticides (aka, “neonics”) and the health of honeybees. Neonics were introduced in the late 1990s without incident as a less toxic replacement for the mass spraying of organophosphate and pyrethroid pesticides, which are both known to kill bees and wildlife.

You’ve likely seen the hysterical headlines about the “Bee-pocalypse” caused by neonics. That’s not the Precautionary Principle – that’s a total misrepresentation of the scientific reality.

But bee deaths are nothing new. The current “crisis” prompting the EU’s reaction is an age-old problem in the bee world: unpredictable bee deaths. They’ve occurred periodically for more than a century. And it’s so easy to blame evil pesticides. Unfortunately, that’s not the case. As an article in Forbes commented, “Activists often coalesce around an issue and then come up with a simple but sometimes simplistic narrative to frame it. Strident opponents of modern agricultural technology initially blamed GMOs for bee deaths, and some still make that claim, although there is zero evidence to back it up. When that didn’t get traction, the focus switched to neonics.” Publications ranging from Mother Earth to Mother Jones jumped on the “ban neonics bandwagon.”

Alas – it’s not nice to try to pull a fast one on your mother. Here are the facts.

In December 2013, the European Commission banned the use of neonics, for two years. The moratorium (driven by the precautionary politics that today dominates so-called science-based regulation in Europe) took effect just as numerous new studies shed increasing doubt on the belief that neonics play a central role in bee health. Scientific American’s Francie Diep noted in a recent article sub-headlined “why colony collapse disorder is not that big a deal anymore,” North American honeybee colony numbers have been stable for years at about 2.5 million even as neonics usage became more widespread.

And a brand new study (published in the March 18, 2015 journal PLOS ONE), shows that neonics do not harm honey bees at real-world dosage levels. According to the paper, ““Everyone is pointing the finger at these insecticides. If you pull up a search on the Internet, that’s practically all anyone is talking about,” said Galen Dively, emeritus professor of entomology at UMD and lead author of the study. “This paper says no, it’s not the sole cause. It contributes, but there is a bigger picture.”

And the US Agriculture Department and the EPA convened a working group to address that very question. Their report concluded that neonics, while a contributor, were way down the list of possible causes.

"It seems that the White House is following the same path. Staffed by many environmentalist "true believers," the Obama administration has already implemented both product testing and labeling requirements for neonics before it's own Taskforce on Pollination completes its recommendations."

Alas, the EPA just announced a couple weeks ago that they’re halting new use approval on chemistries that have already been approved until new studies can be done, essentially a precautionary move.  The implications of moving to the precautionary principle doesn’t just mean new, innovative technologies don’t get approved, it means innovators may question their desire to pursue and invest in new technologies.  Embracing the Precautionary Principle has serious and deliterious implications for feeding a growing planet in a cheaper, safer, and more sustainable manner -- with no guarantee of improving pollinator health at all.

That’s just bee-ing and nothingness.

I’ve just finished three fascinating days in Sharm El Sheikh at the Second Arab Conference on Food & Drugs. It was all business – and I didn’t even mind not getting any time to enjoy the Red Sea beaches.

Delegates from the Levant to Morocco had a lot to say and share. The fundamental take-away was that the Arab world is serious about coordinating their efforts in healthcare in general and in regulatory affairs specifically. “Convergence” and “harmonization” were the two key words of the event.

(The Middle East/North Africa Region – MENA – consists of 22 nations – but just 2% of global pharmaceutical sales.)

I was honored to present a plenary address on “Advancing Medicines Quality via New Strategies in Bioequivalence Regulations, Pharmacovigilance Practices, and the Identification and Management of Substandard Pharmaceutical Events,” as well as chair the event’s panel on pharmacovigilance, sharing the panel with governmental thought leaders such as Dr. Amina Tebba (Morocco), Dr. Amr Saad (Egypt), Dr. Emad Munsour (Qatar), and leading global policy experts Dr. Hisham Aljadhey (King Saud University), and Michael Deats (WHO). I also participated on a panel discussing the urgency of IP, as well as another on biosimilars – specifically calling out the vexing debate over nomenclature, physician notification, and therapeutic substitution.

With healthcare policy (as with life in general) – wherever you go, there you are.

Not surprisingly, much of the conversation centered on controlling costs – specifically pharmaceutical costs, without (alas) the appropriate balance of time spent on the pennywise/pound foolish consequences of many of these policies. The IP panel tried to add balance to that debate by strongly presenting the facts on the value of innovation.

Dr. Rasha Ziada (Egyptian Ministry of Health) made the important point that if a pricing authority doesn’t take outcomes into consideration, it will lead to overall price distortions. Amen. And Dr. Ola Ghaleb (Ministry of Health, United Arab Emirates), spoke about the UAE’s strategy of performance-based risk-sharing arrangements – but also how politics can derail any decision-making process. Her honesty was refreshing. Net/Net -- Outcomes is now capitalized and bolded in the international lexicon of healthcare policy.

While many of the presenters discussed the value of sharing pharmaceutical economic data across borders, there was not an equal counterbalancing discussion of the value of sharing clinical data for approvals and outcomes-based decision-making processes. But there was certainly an effort (both on many of the panels as well as during the breaks and after hours) to stress the urgency of this agenda. The good news is that many, many speakers (sometimes in passing and other times passionately) made the point that it mustn’t just be about “getting the lowest price,” but also appropriately pricing the most clinically effective treatments. Bravo.

Many of the delegates said (from the floor as well as in conversation) that the conference was useful – but that action is required. In short – talk is cheap. My feeling (speaking privately with senior government officials from many of these nations) is that there is serious momentum for change (and even reinvention). But only time will tell.

As Deming said, “Change is not required. Survival is not mandatory.”

Or as the Egyptian saying goes

كلنا فى نفس القارب
We are all in the same boat.

A new article in Nature Medicine challenges one of the biggest myths of the global healthcare debate. The title says it all:

Questions raised about whether compulsory licenses get best prices

For those who follow the facts rather than the rhetoric, the findings are not surprising -- he use of compulsory licenses by developing countries to obtain cheaper drugs for HIV and AIDS by circumventing patents has not been the best strategy for achieving the lowest prices over the past decade. Instead, the best prices were regularly obtained by countries that procured their drugs through voluntary negotiations, often facilitated by third parties such as UNICEF or the Global Fund to Fight AIDS, Tuberculosis and Malaria.

The facts are indisputable.

Amir Attaran, who studies law and population health at the University of Ottawa in Canada, compared the prices of antiretroviral medications obtained through compulsory licenses in several countries with the median price achieved by peer countries for the same drugs through international procurements in the same year. Compulsory licensing did result in lower drug prices compared with the price on offer before the license was issued, but of the 30 cases of compulsory licensing from 2003 to 2012 for which reliable data was available, the median price achieved through international procurement was lower for 19 of them—in the majority of cases by more than 25% (Health Aff., 34, 493–501, 2015). The effect was strongest in the poorest countries, where in six out of seven cases the procurement price was more than 25% lower than the compulsory license price.

Attaran says the results suggest that countries should not rush into using compulsory licenses until they have exhausted all other options. “Countries can save money using compulsory licenses, but they can save more by negotiating and using international procurement channels,” he says. “If saving money is paramount, then compulsory licenses may not be the optimal strategy.”

Myth: Technology transfer as sound healthcare policy

The price differential was highest when countries issued a compulsory license to manufacture the drug locally. The largest disparity was seen in 2012, when Ecuador licensed the production of a combination treatment of the drugs abacavir and lamivudine. The median price achieved by other countries for that drug combination was ten times cheaper. This is because to produce the drug locally a country may need to build up a manufacturing base from scratch, and economies of scale are lost. Attaran says there are valid reasons a country may want to do this, for example to ensure a secure supply or to address concerns about manufacturing processes, but then price can no longer be the driving force for the decision. “If they want local production, it's going to cost them,” he says.

According to Attaran “This is not an indictment of compulsory licenses, but a question of judgment,” he says. “It's not in anyone's interest to advocate for something that is not supported by evidence.”

The complete article, worthy of careful examination, can be found here.

The Wall Street Journal writes, “A well-known hedge-fund manager is taking a novel approach to making money: filing and publicizing patent challenges against pharmaceutical companies while also betting against their shares.”

That person is Kyle Bass.

The complete article can be found here.

It’s an important read and should call attention to an issue that, unless firmly and expeditiously addressed, could lead to a serious reduction in innovation.

Mr. Kyle’s strategy is akin to buying gasoline and matches and then advising arsonists to invest in fire insurance. Far from his claim of being an advocate for affordable medicines, Mr. Kyle is just another scam artist qua patent troll. Patents, according to Abraham Lincoln, “add the fuel of interest to the passion of genius.” Mr. Kyle’s proposition just adds fuel to the fire of greed. He is nothing but a healthcare arsonist.

In light of the recent court decision that Roche adequately warned of Accutane risks (based on labeling and warning literature issued to physicians), it is timely to remind those in the public health community that the FDA’s most potent weapon in the battle for accurate, timely, “rational” prescribing is clear, approved labeling.

And yet the debate over who should make decisions about safety and efficacy – and on what evidence those choices should be made is still blazing. Today, the FDA has the responsibility to determine approvals and labeling language based on a scientific review of the evidence. Should this authority be ceded to the tort bar?

The dedicated members of our legal profession have always provided, and continue to provide, vital protection against those who would prey on consumers or intentionally try to pass off harmful products. The threat of litigation can be an important disincentive to many predatory behaviors.

The problem is that the current liability system doesn’t reward lawyers who focus on these real public health concerns. Instead, the most experienced and well-financed law firms know that the biggest payouts regularly go to those who take advantage of the FDA’s best efforts to promote the safe and effective use of medications.

More and more often, these “mass tort” firms specialize in taking a new product-warning label or withdrawal decision by the FDA and viewing it as a signal to go forward with all guns blazing. Their bullets, unfortunately but not unpredictably, hit multiple innocent targets.

Have a look at this new paper from the Journal of Commercial Biotechnology – and weigh in on this important issue. Maybe when our elected officials understand that it’s the health of their constituents versus the pocketbooks of lawyers, our public servants will finally get serious on tort reform.

Accutane Agonistes

  • 04.07.2015

Accutane’s Warning Labels Sufficient, Judge Rules

Drug Industry Daily

Roche adequately warned of the risks of ingesting acne drug Accutane after April 10, 2002, a New Jersey judge ruled last week, resolving lawsuits filed by people in the state who used the product since that date.

The manufacturer’s labeling and warning literature issued to physicians accurately disclosed the potential risk of inflammatory bowel disease, says Superior Court of New Jersey Judge Nelson Johnson in his summary judgment.

Last week’s ruling is limited to cases involving New Jersey plaintiffs who took Accutane since the most recent warnings were issued. The court intends to determine the effect on cases in other states which could involve up to 800 plaintiffs who are being given a chance to convince the court that some other states’ law with more lenient standards could be applicable.

Counsel from both sides will submit legal briefs regarding which jurisdictions permit decisions on label adequacy based on law, and which ones have a heavier burden of proof than New Jersey. A hearing is set for May 11 to finalize a list of all lawsuits impacted by the ruling.

Roche has for many years provided strong warnings of the potential relationship between Accutane and IBD, although the emerging science has largely ruled out any connection, spokeswoman Tara Iannuccillo tells DID.

The ruling should act as a teaching moment for patients and doctors that labeling is important, that all drugs have risks and that those risks need to be carefully explained to patients, says Peter Pitts, president of the Center for Medicine in the Public Interest.

“This ruling reinforces the need for significant tort reform. These ultimately come down to the category of being frivolous lawsuits. Obviously, people took the drug and had negative effects, but that is completely predictable and it’s part of the proposition of taking any drug,” he tells DID.

The plaintiffs did not respond to a request for comment by press time.


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.

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