Pfizer’s Adverse Event Reporting Warning Letter: Those Who Don’t Learn History…

Maybe its summer re-run season, or the fact that the hottest new movies are Karate Kid and the A Team, but we are feeling a lot of déjà vu lately.

An FDA advisory committee to review the safety profile of Avandia? We’ve definitely seen that before. A big pharma company in the hot seat for manufacturing/quality control issues? This time its J&J, but Schering-Plough and Wyeth and Warner-Lambert have all seen this movie before. (Hmmm…Though none of those three companies is independent anymore…)

But what really sealed the deal was this item: Pfizer getting a Warning Letter from FDA citing the company for failure to forward adverse event reports to the agency in a timely fashion. Not just the letter, but—as we noted in The Pink Sheet—the fact that the letter leaked to the media shortly after receipt by the company, and hence got much more media attention that it might otherwise have received.

We couldn’t shake the strange feeling that we had seen this one before too. It took some digging in the archives, but we were right. In April 1996, Pfizer got a letter from FDA citing the company for failure to submit adverse event reports to the agency in a timely fashion. Not only did Pfizer get the letter, but FDA leaked it right away to the AP—the exact same outlet to get the letter this time around.

They say history doesn’t repeat itself, but this is as close as it gets. Different products, but same company, same issue, and same attention getting strategy by the agency, 14 years later.
Okay, so what does that tell us, other than that The Pink Sheet’s archives are an incredible resource, and that FDA’s communication tactics are tried and true?

Well, first off there is some sort of lesson in this for Pfizer. Yes, 14 years is a long time and it is ridiculous to draw any conclusions from that coincidence about some sort of corporate history of sloppiness in adverse event reporting. Heck, the latest letter focuses computerized systems that apparently didn’t work as well as Pfizer hoped; the very idea of computerized adverse event reporting was new in 1996.

But still, it does say something about Pfizer’s failure to learn from experience. After all, FDA used the exact same playbook on this issue that it followed 14 years ago, by coincidence or otherwise. For the same company to be the same target when FDA decided to set an object lesson is at least a little bit embarrassing.

There is a more important implication for everyone else. Today, just like 14 years ago, the point of FDA’s strategy is clear: the agency wants to get everybody’s attention on the issue of adverse event reporting. Picking on Pfizer is one thing, but the purpose of the leak is to make sure other companies review their systems and correct any similar problems. It is much easier to leak one letter than to inspect every pharma company for similar issues.

Here’s a bit more history. At the start of 1999, FDA sent two more Warning Letters, citing Novartis and Berlex for failure to submit timely adverse event reports.

That suggests that most manufacturers got the message when Pfizer was warned, and that FDA was willing to give them a bit of time to adjust. But, in FDA’s eyes at least, not everyone got the message quickly enough.

We’ll see if that piece of history repeats this time around.

Drug Safety 2010: Nissen Meets With FDA Leadership as the Avandia Advisory Committee Meeting Looms

The most important single event for FDA’s drug review in 2010 and possibly beyond is coming this summer: the advisory committee re-review of GlaxoSmithKline’s diabetes drug

Since passage of the landmark FDA Amendments Act of 2007, the drug approval climate at FDA has improved steadily. To view The RPM Report’s analysis on the drug approval climate, click here

It appears one potential conclusion that can be drawn is that FDA’s comfort level with the postmarket control and monitoring tools given to them through FDAAA is adding confidence to approval decisions.

But the Avandia re-review could change all that. Whether FDA chooses to pull Avandia from the market, keep the drug on the market, suspend use temporarily or further restrict its use, the agency must ensure that it does one thing: make a credible decision. Any outcome deemed to be unsatisfactory by FDA stakeholders in Congress, and the experts they listen to, puts the improving drug approval momentum in real jeopardy.

Just to recall briefly: In May 2007, a meta-analysis by Cleveland Clinic cardiologist Steve Nissen published in the New England Journal of Medicine found that Avandia (rosiglitazone) was associated with over a 40% increase in heart attack risk. The House Oversight & Government Reform Committee put together a hearing before FDA could respond to the study. In July 2007, FDA convened the Endocrinologic & Metabolic Drugs Advisory Committee and the Drug Safety & Risk Management Advisory Committee to assess Avandia’s future.

The joint committee voted 20-3 that the drug increases cardiac ischemic risk but subsequently voted 22-1 against withdrawal of the TZD. The panel meeting surfaced an “internal disagreement” between the Office of New Drugs and Office of Surveillance & Epidemiology over whether to withdraw rosiglitazone over heart attack risks.

On October 2, 2007, FDA’s Drug Safety Oversight Board voted (8-7) to keep Avandia on the market. The non-public vote was questioned by ranking Senate Finance Committee Republican Charles Grassley (Iowa) due to the lack of transparency. On November 14, 2007, FDA issued a black-box warning for Avandia warning of heart attacks. GSK agreed to conduct a long-term postmarket safety trial of Avandia compared to competitor Takeda’s Actos to confirm a higher CV risk for rosiglitazone; the trial was named TIDE. The TIDE trial is expected to be complete in 2015.

The Senate Finance Committee released a major report on February 22 bringing to light internal emails and memos related to Avandia and heightened CV risks. On February 26, House Agriculture Appropriations Subcommittee Chair Rosa DeLauro (FDA’s chief appropriator) gave a detailed critique of GSK’s RECORD study, which the company maintains supports Avandia’s safety profile.

Now FDA is scheduled to hold another re-review of Avandia, likely July 13-14.

"Congresswoman DeLauro is looking forward to the advisory committee meeting and its findings,” a spokesperson for DeLauro says. “She believes that the TIDE trial is unethical and should be halted immediately, and has urged the FDA before to remove Avandia from the market until a truly independent, science-based advisory panel can evaluate the safety and effectiveness of the drug.”

DeLauro and her staff met with FDA Principal Deputy Commissioner Joshua Sharfstein and Assistant Commissioner for Legislation, and former staffer to Rep. John Dingell, Jeanne Ireland on May 20. The topic? “Drug safety.”

DeLauro isn’t the only one meeting with FDA leadership. Nissen recently met with FDA Commissioner Margaret Hamburg and Sharfstein to make the case that the TIDE trial was unethical and that Avandia needed to be withdrawn.

The major threat to the approval environment and the current FDA review structure is that an outcome on Avandia that is viewed as lacking credibility will energize those who want to split the Center for Drug Evaluation & Research into two separate centers or offices. A split would still be a long-shot, but a possibility nonetheless.

“As far as the FDA’s organization, the Congresswoman believes that serious consideration should be given to creating two independent offices within FDA – one that would be responsible for reviewing drug applications, and another for post-market surveillance,” the DeLauro spokesperson says. “It is something she has been concerned with for awhile, and the Avandia case serves as a reminder of just how important it is to address this situation.”

Here are a few points to consider as the Avandia re-review approaches:

1) How many advisory committee members will be assembled? In July 2007, there were 23 panel members convened for the meeting. That is a large number of committee members, many of whom were given temporary voting status. The makeup of the committee will be equally important in terms of the balance between drug safety specialists and E&M committee panelists (to view the 2007 final roster, click here).

2) Will the full Actos safety data be presented? Our understanding is that FDA asked both GSK and Takeda for every shred of data related to Actos and have had the data for “months.” Whether or not those data are formally presented at the meeting will go to the heart of the credibility question whatever the committee and FDA decide to do with Avandia. The current buzz in Washington is that not all of the Actos data will be presented, but it is still too early to determine whether that will actually be the case in the end.

3) Will Nissen present? At the July 2007 meeting, Nissen did not make a formal presentation of his meta-analysis—the whole reason for the existence of the panel meeting—to the advisory committee. Instead, he sat in a chair along with the rest of the audience. Something similar happened with Sanjay Kaul, a Cardio-Renal Advisory Committee member who was barred from the advisory committee review of Eli Lilly’s anti-clotting drug prasugrel (to read The RPM Report story, click here).

4) Hamburg and Sharfstein have gone to great lengths to brand the Obama Administration’s FDA as a public health agency. The Avandia re-review represents the first major prescription drug safety, public health issue. How will they react? Hamburg has already gone to IoM for ethical and scientific guidance on postmarket studies (to read our analysis in The RPM Report, click here). Probably the best outcome for the drug industry at large would be a risk evaluation and mitigation strategies (REMS) program that controlled the use of Avandia, monitored patients on the drug, and provided FDA with valuable data on its cardiovascular risk profile. That result would validate the use of FDA’s drug safety authorities under FDAAA, hold together FDA’s current regulatory structure and keep the approval momentum going. But is that enough of a public health message for Hamburg and Sharfstein?

5) There are a number of important FDA officials who will be directly affected by the final decision on Avandia--maybe none more than the ones who will make that decision. Hamburg and Sharfstein will bear the brunt of public scrutiny around the decision. Perhaps no one will be under the microscope more than CDER Director Janet Woodcock, who concluded that Avandia should remain on the market in 2007 with stronger warnings. This is a major issue for FDA. Woodcock is held in high regard as a strong leader, effective manager, and there are few individuals at FDA who understand its operations—and runs them as efficiently—as Woodcock. While the FDA drug safety players are the same—Gerald Dal Pan and David Graham—the drug review management is different compared to 2007. In 2007, CDER Office of Drug Evaluation II Director Robert Meyer gave a public refutation of the conclusions drawn by Graham and Dal Pan that Avandia had to be withdrawn. Meyer is no longer at FDA and Curtis Rosebraugh is the current ODE II Director. However, Mary Parks was and remains the Division Director for Metabolic and Endocrine Drug Products. Both Rosebraugh and Parks will be important officials on the Avandia re-review. Lastly, CDER Deputy Director for Clinical Science Bob Temple will play a role in the Avandia decision but it is unclear exactly what kind and how big a role. Temple has presented publicly about FDA’s tough decision-making when it comes to taking a drug off the market.

There is still a lot of time before the advisory committee: much could change and there are sure to be surprises just as there were in 2007. But it would be an understatement to say there is a lot riding on Avandia.

Belatacept Advisory Committee: One Sign of the Times

Bristol-Myers Squibb is, as our colleagues at "The Pink Sheet" pointed out, facing a bit of an uphill climb during today's advisory committee review of the transplant drug belatacept.

But one item in the preview materials posted by the Food & Drug Administration caught our eye as a sign of the times for advisory committees in general: FDA issued a formal conflict-of-interest waiver for Richard Mann, who heads the kidney and pancrease transplantation program at Robert Wood Johnson Medical School.

Under new rules set by the FDA Amendments Act, the agency is directed to review potential conflicts-of-interest of advisory committee members carefully, and issue waivers sparingly. (You can read more about this issue in The RPM Report, here.)

In this case, the agency wanted Mann to serve as a temporary voting member, but spotted a potential conflict: he was listed as a co-investigator on a trial involving "competing products to belatacept." The study drugs are not identified in the waiver document, but it does explain the circumstances.

Mann was listed as a co-investigator "as a matter of policy" by the medical school; he is not an active participant in the trial. In fact, he "has filed the appropratiate paperwork" to have his name removed from the study. Moreover, the size of the potential conflict is "$0-$50,000 per year."

However, FDA notes, the fact remains that his employer has an interest in competing products, and therefore Mann has an "imputed conflict of interest."

The agency considered 10 other transplant nephrologists for the committee. Four couldn't attend, one did not submit the paperwork for review, and the other five were "recused to conflicts of interest"--presumably more serious ones than Mann's.

In other words, Mann was the only transplant nephrologist available for the meeting who didn't have a direct conflict of interest. Waiver granted.

But that also means one less waiver for the agency to use later in the year. Under FDAAA, supplies of waivers are limited--essentially to a small percentage of committee members overall--so issuing this one means one fewer to use later on. And, as the standard applied to Mann shows, it will be hard to seat committees without using at least some of those precious waivers--especially for specialty products.

XenoPort Experiences Restless Investor Syndrome

File this one under Regulatory Setback Syndrome. The FDA decision to issue a complete response letter to XenoPort and GlaxoSmithKline for their Horizant drug to treat Restless Leg Syndrome appears to have stunned the drugmakers. In a conference call this morning with analysts, XenoPort chief executive Ron Barrett confessed he didn't see it coming until the FDA missive arrived yesterday.

"It certainly did surprise us," he told the listeners, insisting the issue was never raised in any discussions with the agency during the entire pre-approval processs. "Many of the activities that you would expect to happen going into a PDUFA date had and were happening, including the REMS, and this one came out of left field."

What went wrong? The FDA bounced the drug because a trial showed a cancer risk in rats, specifically a prevalence of pancreatic acinar cell tumors in male rats. Interestingly, a similar finding showed up in Pfizer's Neurontin (gabapentin), which is approved to treat refractory epilepsy, and Barrett said the strength of the signal was no worse than what was seen with the Pfizer drug.

The FDA acknowledged that findings in lab animals don't necessarily translate into risk in humans, Barrett continued, adding that the agency "noted that gabapentin products have been available for over 15 years, and they do not appear to be associated with a clinical signal for pancreatic cancer based on analysis of spontaneous reports in the adverse event reporting system."

The issue for the FDA, though, is that treating epilepsy is a more serious matter than Restless Leg Syndrome, a line of thinking that may bolster those who have criticized the marketing surrounding the condition, even though it is deemed to be kosher by the National Institute of Neurological Disorders and Stroke (take a look).

For now, the implications for XenoPort are more immediate and severe than any marketing debate. Glaxo already announced plans to exit research into pain, and Barrett concedes their deal for the drug may be up in the air, possibly threatening further development of Horizant to treat neurothropic pain, where a Phase II trial failed last year, and migraines. Barrett, however, refused to offer any definitive insights on this particular topic. "The question of risk-benefit is something that is going to have to be probed for each indication."

In response to a question about Glaxo's ability to end the deal based on development setbacks, Bennett offered this sobering reply: "I think it's fair to say that any license agreement of this type is going to have termination provisions. And without speaking to language that might be redacted, I think it is reasonable to expect that this agreement is no different than that GSK would have the ability to terminate for reasons that include what you have articulated, among others. So I think people should understand that a termination by GSK is possible in the wake of this news, as well as in the wake of other developments."

Consequently, XenoPort is now suffering from Restless Investor Syndrome - its shares are down a whopping 67% in midday trading to about $6.54 on nearly 10 times normal trading volume. Given these events, Bennett has to be sorry Horizant isn't already available to treat migraines.

arrow thx to austinsdkeys on Flickr Creative Commons

FDA's Jenkins Sounds Off on Incomplete NDAs

Earlier this week, FDA issued a Refuse to File on Merck-Serono's cladribine application, meaning the agency felt the NDA was sufficiently lacking that it didn't want to begin a review yet.

The topic of Refuse to File letters came up today at Windhover's FDA/CMS Summit. No drug or company was mentioned by name, however; the discussion was prompted by an audience question and warmly embraced by FDA Office of New Drugs director John Jenkins.

FDA, Jenkins said, has for the most part held up its end of the bargain created 17 years ago by the industry-FDA agreement known as PDUFA. "Most of the time," he said, FDA reviews drugs in the appropriate time window. But too often industry is developing the drug on FDA's review clock. If industry really expects FDA to stick to that model, he said, applications need to be complete so that questions won't arise just before the PDUFA date because information is still coming in from drug sponsors during the review process.

If industry's complete response letters were released, "would you make sure your application is complete before you submitted it?" asked Jenkins. Would senior executives wake up to regulatory realities? Jenkins suggested that companies "do the math some time." Delaying an NDA a few months until it's truly complete can save double that time on the extended review process that results from incomplete applications.

We can't be sure why FDA dinged Merck-Serono's application; that information is, for now, secret. In a recent feature about potential orally available multiple sclerosis therapies we duly noted that Merck Serono's chances with its first-to-NDA oral therapy cladribine weren't a 'slam dunk'. The drug's efficacy looks great in one Phase III trial in relapsing remitting MS patients, and side effects in this therapeutic space are navigable, for sure (just ask Elan and Biogen Idec). But that's just one trial, as we also noted, and the drug hasn't been tested against an active comparator. It was never clear how FDA would react to that.

FDA's rebuttal might have been due to some other deficiency unrelated to the lack of a confirmatory Phase III trial (which will take the company many more than just a few months, given the time frames for large MS trials). For its part the company has stated that it will get together with FDA as soon as possible to discuss the issue and other Phase III studies of oral cladribine which are ongoing in different forms of MS.

image from flickr user wilhei55 used under a creative commons license

Bump in the Tobacco Road: Reimportation Returns in FDA Bill

Chairman Henry Waxman (D-California) is very close to achieving one of his objectives stretching back more than a decade: granting explicit authority for the Food & Drug Administration to regulate the marketing and development of tobacco products. The Family Smoking Prevention and Tobacco Control Act (HR 1256) passed the House on April 2 by a commanding 298-112 vote and was cruising toward Senate passage this week.

But then Sen. Byron Dorgan (D-ND) hauled out one of his long-term favorite projects (drug reimportation) and created a nasty hurdle in the final stretch of Waxman’s long journey. Dorgan (D-ND) proposed the “Pharmaceutical Market Access and Drug Safety Act of 2009” on June 2 to be introduced as an amendment to the anti-smoking bill. Dorgan has five of long-time allies on the issue: Olympia Snowe (R-ME), John McCain (R-AZ), Debbie Stabenow (D-MI), Bernie Sanders (I-VT) and Amy Klobuchar (D-MN).

There is an interesting irony for Waxman as Dorgan tries to ride the success of the smoking bill. Waxman has never been a proponent of permitting drugs from lower cost markets to be imported to the U.S. as a cost control measure. That approach has been treated by Waxman and other prominent Democratic leaders in the health area as a distraction from more direct ways to address drug prices and a threat to FDA’s ability to protect quality manufacturing for pharmaceuticals.

If Dorgan can link drug reimportation onto the tobacco bill, Waxman may be faced with having to accept a provision he has fought for years if he wants to move forward with one of his top public health priorities.

Experience says that Dorgan will fail to attach reimportation in any meaningful way. Advocates for a strong FDA are watching the Dorgan amendment effort with worry and distaste. Adding tobacco authority and working to improve food control are big projects by themselves. FDA doesn't need to try to undertake the complicated system for assuring safe imports of drugs marketed in Canada or elsewhere. Congress has foiled the reimportation attempts many times in the past or added provisions that made in difficult or impossible to implement. But like Waxman’s tobacco crusade, reimportation seems to be an issue that won’t go away.

The environment around the reimportation debate is changing also. When the proposal first came up, opponents were able to raise the convincing threat of unsafe or poorly manufactured products from outside the US slipping into the domestic drug supply if reimportation were passed.

However, with many manufacturers outsourcing production of active ingredients to a wide variety of low-cost manufacturing locales, they are effectively eroding their own defense-of-quality argument. Domestic suppliers (brand and generic) have had enough well-publicized problems assuring the quality of their products with components from overseas to create a more favorable environment for reimportation. It is one of those Congressional pet projects which might linger around long enough to find the right time for enactment.

Kind of like FDA regulation of tobacco.

FDA and EMEA: Minding the Gap

“EMEA is not the FDA of Europe, and the FDA is not the EMEA of the United States.”

That’s how Richard Pazdur – the head of FDA’s Office of Oncology Drug Products – started off a panel on oncology regulatory initiatives at ASCO on May 30. “We recognize that there are different laws, different interpretations of existing laws and different cultural issues that can be brought into play in making regulatory decisions,” he added.

But with consistency, and transparency, in mind, the two regulatory bodies do practice openness. FDA’s entire oncology review team has monthly teleconferences with key EMEA officials. They go over pending regulatory actions, recent meetings with sponsors, proposed regulatory initiatives and even occasional staff exchanges (a regulate-abroad program?).

There is also a free exchange of documents – minutes from end of Phase II meetings, important regulatory letters. “Really the oncology program with this interchange has been one of the models that the FDA and the EMEA want to emulate in other therapeutic areas,” Pazdur said.

Still, Pazdur, who received a personal plaudit for his stewardship of cancer drug approval process with a career recognition award, kept honing in on the differences between the European regulatory system and the FDA process. The way Pazdur referenced some of those differences could constitute a wish list for additional authorities the FDAer would like to have.

One key difference is in the enforcement mechanisms for early approval of innovative therapies – accelerated approval in the US, and conditional approval in Europe. Pazdur deems these functionally equivalent: “it’s a matter of terminologies.”

“But there are differences here. Both of the programs have options to take the drug off the market if clinical benefit or subsequent trials are not done,” Pazdur pointed out. With its longer experience with accelerated approval (EMEA only adopted conditional approvals last year), there have been more tests in the US. And even when a drug has failed in its mandatory trial to confirm the benefit that was the basis of the accelerated approval (AstraZeneca’s lung cancer therapy Iressa), FDA opted not to outright rescind the marketing authorization, instead laying on marketing restrictions and limiting distribution. Still, “most of our drugs have not faced that issue of coming off the market,” Pazdur admitted.

The US legislation on accelerated approval stipulates that sponsors should approach confirmatory trials with “due diligence” – which, Pazdur added, “really is in the eyes of the beholder. Let’s face it, it does not have a legal definition. Whereas I noticed the Europeans were a bit more clever and probably learned from our experience. They put a one-year review, and we don’t have that.”

The EMEA’s Francesco Pignatti made clear that they don’t really have the explicit authority to rescind the approval for compliance reasons, though the one-year re-review remains untested. “It’s only in the case of adverse new information that one could see this change,” he predicted. But the opportunity to reconsider the emerging knowledge of a drug’s risk-benefit was clearly an aspect Pazdur admires.

The FDA official expressed some frustration with the way sponsors handle confirmatory trials for accelerated approval. “Several ODAC meetings have discussed the sometimes lack of due diligence on the part of sponsors in fulfilling these commitments,” Pazdur pointed out. “They are mandatory commitments and should be taken quite seriously by the sponsor.”

There too the EMEA built in a mechanism that FDA would find useful: the European regulators can impose financial penalties if the postmarketing studies are not delivered as agreed.

Consultation with external experts is one area where Pazdur seems to prefer the US system, though he handled the comparison with diplomacy. Unlike the FDA advisory committee system, the EMEA’s Scientific Advisory Group meetings are closed to the public. They’re even mostly closed to the companies involved (there are open portions of the meeting for the sponsor to make a presentation, but then the discussion is closed off again). Pazdur questioned whether the process would be improved or hindered by having public involvement.

Without any experience with that, Pignatti declined to speculate, although he did note the EMEA is “rather far” from having public access for those meetings. Pazdur, however, jumped in – having attended both SAG and CHMP meetings “and obviously the ODAC meetings.”

“To be honest there’s a remarkable similarity as far of the discussions,” he said. In fact, the consistency – reassuringly – holds up with the internal regulatory processes as well, he noted. “Although we’re independent agencies and usually have not discussed the applications prior to our teleconferences, many of the exact same issues come up. And although people love to point to the differences between decisions that the EMEA and the FDA make, by far there’s more similarities than any differences.”

Despite the “lack of transparency” Pazdur noted in the European system for external consultations, the FDAer openly admired the transparency that EMEA gives regarding negative regulatory decisions. The EMEA publishes its negative opinions and reviews on withdrawn applications as well as the positive opinions. “One of the issues that we have in the FDA, which is quite problematic for those of us that work in the FDA,” Pazdur noted, is that when the agency does not approve a drug, the review documents and even the complete response letter that lays out the deficiencies in that application are not released to the public. Companies could release that information (although trust us, they don’t), but FDA is tied from even commenting.

“So this I think is one of the main reasons that we have this apparent lack of transparency, because we cannot release negative information. When we approve a drug, all that information goes out on the web. But for non-approvals, it’s truly the black box warning, so to speak, in its ultimate form,” Pazdur said. --Mary Jo Laffler

Conspicuous Consumption: FDA Makes TB a Priority

Margaret Hamburg has only been on the job as commissioner of the Food & Drug Administration for two days, so it is obviously too early to pronounce on winners and losers in the Hamburg era. Except in one case: it already looks like the Hamburg years will be good ones for companies pursuing new therapies or vaccines for treatment of tuberculosis.

After all, Hamburg’s role two decades ago in combating drug resistant TB as New York public health commissioner was one of the defining elements of her resume when she emerged as the nominee for FDA commissioner. As she told the Senate HELP Committee during her confirmation hearing earlier this month, New York’s “rapid response to an epidemic of drug-resistant tuberculosis became the model worldwide.”

But it’s not just Hamburg talking about TB.

FDA’s new chief scientist—Jesse Goodman—highlighted a TB vaccine as an example for the need to focus on global public health priorities during a keynote address at the Food & Drug Law Institute annual meeting in April.

“There are billions around the world who clearly need an effective TB vaccine,” he said, citing an analysis by BIO Ventures for Global Health indicating that the market for such a vaccine would exceed $1 billion—even without sales in the US or other developed economies.

That’s not all: “If we had a highly safe and highly effective TB vaccine it would probably make sense to use it in this country,” Goodman added, noting “the chaos” that followed one traveler returning to the US with extremely drug resistant TB. That’s music to the ears of companies like Sanofi and GSK, which are developing TB vaccines. (You can read more of Goodman’s remarks to FDLI in The RPM Report.)

Then there is an upcoming meeting of FDA’s Anti-Infectives Drugs Advisory Committee June 3 to discuss “issues related to the development of drugs for the treatment of tuberculosis, including drug resistant tuberculosis.”

“Areas of discussion include diagnosis, treatment duration, study design (such as endpoints and duration of follow up) and safety issues,” the meeting announcement says. (We’ll have coverage of the meeting itself in The Pink Sheet next week.)

The meeting was announced by FDA March 12, one week after we broke the story of Hamburg securing the White House nod for FDA. We missed the coincidence at the time, but in hindsight it’s a clear indication of one priority for the new FDA leadership. (Yes, the TB meeting was being planned before Hamburg was picked—but then again, Hamburg was on the HHS transition team…)

A search of our Inteleos database shows at least 34 drugs and vaccines in development for TB. The Hamburg years should be good for those projects.

Fighting Like a Wolfe Against Johnson & Johnson

There are certain codes of conduct during advisory committee meetings. Come prepared having thoroughly read the briefing documents. Speak in turn. Don’t discuss the merits of the application over lunch.

Sidney Wolfe isn’t one to stand on protocol.

During the March 19 Cardiovascular-Renal Drugs Advisory Committee review of Johnson & Johnson’s anticoagulant rivaroxaban, Wolfe, the acting consumer representative, took the unusual step of calling out to an FDA drug safety reviewer—Office of Surveillance & Epidemiology associate director for science John Senior, who was sitting in the audience—to ask him point-blank the very question the committee was being asked to deliberate: whether rivaroxaban should be approved based on the available data.

It was clear from the start that Wolfe wasn't keen on a rivaroxaban approval, and he set up Senior to issue a negative opinion. Wolfe noted the divergent conclusions drawn by J&J and FDA on rivaroxaban’s liver toxicity profile, and the expectation that the drug could be used extensively off-label. Then he asked Senior: “You’ve been involved in this for some time … Do you think it is a good idea to approve now without waiting to see the results of much more data from much longer duration trials?”

The question was significant for a couple reasons. First, it demonstrated that Wolfe isn’t afraid to step outside the typical bounds of advisory committee meetings to make his point. As we’ve blogged before, Wolfe is not your average committee member, and he’s certainly no shrinking violet. And while there is no hard and fast rule against asking an FDA reviewer his or her opinion about an application, to put Senior on the spot was a bit unusual—especially since he was not part of the FDA team at the conference table.

Calling on Senior served another purpose: it was Wolfe's way of getting another public FDA opinion against the approvability of rivaroxaban. OSE was well-represented at the meeting: director Gerald Dal Pan was at the committee table, and medical officer Kate Gelperin delivered a compelling critique of rivaroxaban’s safety profile. But Senior’s reasoned evaluation of the NDA only fueled Wolfe's arguments.

Senior said that while he was “impressed” with J&J's early look of longer-term safety trials (known as the ATLAS study), “I'd like to see more.”

Senior then evoked AstraZeneca's failed anticoagulant ximelagatran (Exanta). FDA should “learn the lessons from ximelagatran,” Senior said. Exanta's heptotoxicity signal did not surface until longer-term studies were analyzed, he reminded the advisory committee. With Exanta, FDA issued a “not approvable” letter, and AstraZeneca's eventually discontinued development. Without reading much between the lines: FDA should take its time with rivaroxaban.

Senior added that only under one circumstance should rivaroxaban be approved without longer-term data: “If it can be shown that the drug is saving more lives than it is risking, then I would think reduction in mortality would trump the risk of liver injury. But I haven’t been convinced that those data are real. I think we need to see that.”

Those statements seem to sum up how FDA—or at least the drug safety office—is thinking about the NDA. As reported in “The Pink Sheet” this week, the good news for J&J is that those longer-term data are available: the six-month ATLAS study has concluded. But time is likely to run out: it is unlikely that J&J can submit the final report and FDA can review it before the late May user fee deadline.

In the end, Wolfe cast only one of two votes against approval. Sanjay Kaul, perhaps best known as the disinvited prasugrel committee member, also actively argued against rivaroxaban. Neither managed to convince the rest of the advisory committee to see things their way. But the Wolfe-Senior exchange still illustrated Wolfe's tenacity in making his point—and his savvy in understanding FDA politics. Like we said before, Wolfe is not your typical advisory committee member.

If FDA Pulls a Drug, Which One Will It Be?

This podcasting stuff is fun, but sometimes we even surprise ourselves.

During our most recent IN VIVO Blog podcast, we (meaning my fellow podcaster Ramsey Baghdadi) made a bold prediction: that there will be a high profile drug safety withdrawal this year, in effect to make the point that it is no longer business as usual at FDA.

We (meaning me) were very surprised to hear that prediction, and frankly disagreed. Its not that we don't think the new FDA leadership will take steps to show its independence from industry, its just that it seems inconceivable that they would go to the extreme of pulling an FDA-approved drug to make that point. More Warning Letters, sure. Tough regulatory responses to manufacturing problems, yes. A clampdown on direct-to-consumer advertising, okay. Heck, maybe even putting a CEO in jail the next time sloppy manufacturing or unethical marketing causes patient harm.

But pulling a drug? That's crazy.

Then we started thinking about it a bit. If you had told us in 1990 that David Kessler would, as commissioner, pull a perfectly harmless national brand of orange juice from the shelves nationwide simply to make a point about truth in labeling, we would have called you crazy. But he did. (Remember Citrus Hill "Fresh" OJ? P&G does.) And he did as part of a frankly anti-regulatory Republican administration, no less.

So, given all the attention that the Democratic leadership in Congress has focused on drug safety--and especially on a few prominent examples where they view FDA as having failed in its public health mission--maybe it isn't so inconceivable that the new commissioner will end up pulling one to demonstrate unequivocally that the "old" FDA is gone forever.

Now, bearing in mind that this is pure speculation on our part, we then got to thinking: if FDA decided to go that route, which drug would they pull?

It isn't too hard to come up with candidates. To our mind, the criteria would be relatively simple: what are the drugs where Congress has raised the most concern, where the impact of a withdrawal would do the most to enhance FDA's credibility as a regulator (in the eyes of those who equate being tough on industry with credibility), and where the commissioner could make the case most convincingly that the drug would never have been approved if the agency knew everything it now knows about the risk/benefit profile.

Here is our top five, but we want to know what you think too. And, to repeat: this to get you thinking about the "what ifs," not a prediction of (or call for) any product withdrawal.

Avandia -- As the poster child for drug safety in 2007, GlaxoSmithKline's diabetes medicine would obviously be vulnerable if the new FDA leadership wants to signal a break with the past. Recall that FDA itself was publicly split on whether Avandia should stay on the market, and that it was the subject of a review by the agency's Drug Safety Oversight Board, which voted 9-8 in favor of continued marketing. The new leadership at FDA could simply reconvene that board--with its new membership in the new Administration, and perhaps convene it in public to embrace the Administration's commitment to "transparency"--and we bet the outcome could easily go the other way. That would certainly make Rep. Henry Waxman happy.

Ketek -- FDA took a grilling for the review of Sanofi-Aventis' antibiotic because of a severe case of clinical investigator misconduct in the pivotal trials. The agency ultimately decided that the dataset in support of Ketek is strong enough without the suspect results to continue marketing. However, the new leadership could easily take the position that there is no way to trust any of the data in the Ketek NDA and therefore that the approval is rescinded. That would make Sen. Chuck Grassley happy.

Celebrex -- Pfizer's celecoxib is the only cox-2 inhibitor left on the market. Pulling it would certainly tell the world that the Vioxx era is over once and for all. To be fair, Celebrex is probably one of the most thoroughly studies medicines ever marketed at this point--but that wasn't good enough for Merck's Arcoxia.And with a big settlement soon to be announced regarding Pfizer's marketing of its cox-2 brands, a withdrawal could play as just desserts.

Accutane -- Roche's off-patent acne drug has been marketed for years under a series of risk management programs intended to minimize the potential for birth defects associated with the drug. Ironically, it is only in the past few years that the agency finally thinks it has a program in place that works. But the risk/benefit ratio for the drug has also been a tough case, given that the drug is for cosmetic use, and that only got tougher when questions were raised about potential risk of suicidality with the drug. And those questions have been one of the toughest issues for FDA politically, since Rep. Bart Stupak's son is among those who committed suicide while on therapy with the drug. If FDA is looking to please its Congressional critics above all else, that step may do more than any other to achieve that goal.

OTC cough/cold remedies -- Incoming deputy commissioner Josh Sharfstein led the charge on relabeling over-the-counter cough/cold products to restrict pediatric use. But is he satisfied that FDA went far enough? He can make the call himself soon enough.

Alright, so what do you think? Take our poll below and we'll post the results next week.

The IN VIVO Blog Podcast: All FDA Edition

Mike and Ramsey make another stab at Three Things in Three Minutes. Running time ... about 8 minutes.

How will new FDA leadership impact the drug industry? What's the story with the Hamburg-Sharfstein tag-team deal? Will a renewed emphasis on food safety split the agency? Will there be a bonus topic? (Of course there will ...) Just click on the IVBP logo below to get started...

Don't forget, you can access the podcast via iTunes also.

FDA Commish To Employees: Keep Quiet or Else!

Frank Torti, the acting FDA commissioner, has an important message for all agency employees--you won't make a peep if you know what's good for you.

In an unusual memo distributed last Friday afternoon, Torti ensured the agency is committed to transparency and “the principles of open government.” But after dispensing with the obligatory qualifier, he then went on to warn FDA employees the agency “must comply with its obligations to keep certain information in its possession confidential.”

He then writes those obligations are spelled out in the Food, Drug, and Cosmetic Act, the Freedom of Information Act (FOIA), the Trade Secrets Act, and the Privacy Act, as well as FDA regulations. But if agency employees violate these provisions, they may face disciplinary sanctions, criminal liability and the FDA could be sued for damages.

Torti cites five sweeping categories of info that must be kept under wraps: trade secrets; confidential commercial info; personal privacy data; law enforcement records and privileged intra-agency and inter-agency documents, such as emails, memos and letters between between FDA employees. This last category can be a veritable treasure trove, however, because it can include opinions issued by FDA employees and materials prepared in connection with litigation – the sort of stuff that makes a good headline.

The missive, which an FDA spokeswoman tells us speaks for itself, may have its roots in a recent pair of embarrassing episodes that stemmed from the discussion or release of what FDA officials may view as privileged info. Earlier this year, nine FDA scientists wrote President Obama’s transition team that the review process for medical devices was ‘corrupted and distorted by agency managers.’

An example surfaced last week in a report in The Wall Street Journal, which detailed how a lobbying campaign overcame internal dissent among FDA staffers, who objected to the approval of a ReGen Biologics device for knee injuries. Former FDA commish Andy von Eschenbach acknowledged the affair was handled poorly.

And last month, the FDA removed Sanjay Kaul, a well-known cardiologist at the Cedars-Sinai Heart Institute in Los Angeles, from a meeting of its Cardiovascular-Renal Drugs Advisory Committee at the last minute over the potential for intellectual bias.

The move caused an uproar after it became known that officials at Lilly, whose prasugrel blood thinner was to be reviewed, called FDA offices prior to the meeting to complain about Kaul, who had been openly critical of the drug. The FDA's head of the Office of New Drugs, John Jenkins, later admitted the "disinvitation" was a mistake.

It's unclear whether the memo is directly related to either of those incidents, or if it was issued for more general reasons, although a good source suggests the recent flaps likely had a lot to do with it, because such memos are rare. In any event, one thing is clear: we managed to get a copy, so it doesn't seem to have struck too much fear in the hearts of FDAers. The irony of it all.

Prasugrel Backlash Doesn't Deter Kaul

Sanjay Kaul doesn’t get discouraged easily.

The very public debacle over Kaul’s potential intellectual conflict of interest with Lilly/Daiichi Sankyo’s anti-clotting agent prasugrel has not deterred the cardiologist from fulfilling his obligation as a member of the Cardiovascular-Renal Drugs Advisory Committee.

According to information posted on FDA website, Kaul will participate in the committee review of Sanofi-Aventis’ antiarrhythmic dronedarone (Multaq). Dronedarone will be his first meeting as a permanent member of the Cardio-Renal advisory committee after being “disinvited” from the February 3 prasugrel panel due to a potential intellectual bias.

At the time, Office of New Drugs director John Jenkins expressed hope that Kaul, a well-known cardiologist at the Cedars-Sinai Heart Institute, would remain a member of the advisory committee, despite that fact that his disinvitation sparked a very public—and at times nasty—post-meeting debate over the integrity of FDA’s advisory committee process. (We’ll have more on that in the next issue of The RPM Report.)

“Dr. Kaul is a new standing member of the Cardio-Renal advisory committee. This would have been his first meeting as a standing member,” Jenkins said in a post-prasugrel interview. “We hope that he will continue to serve and will be a productive member of the committee going forward.”

Jenkins was careful to clarify that Kaul was not to blame for the incident. “He did everything he was supposed to do,” he said. “There’s been some suggestion out there—and maybe it’s even from the FDA press statement—that in some way he did not provide us with the information. That’s not correct.”

“He submitted all the paperwork that was required to be on the committee and to be screened for the committee. And when questions were raised about the abstracts, he responded very promptly.”

Kaul is also expected to participate in the second day of the meeting, which will consider the approvability of Johnson & Johnson’s novel factor Xa rivaroxaban (Xarelto) for use in prophylaxis of deep vein thrombosis. Like prasugrel, rivaroxaban is an antithrombotic, and like prasugrel, it may unseat the standard of care, in this case warfarin/heparinoid therapy.

And if all that isn’t enough reason to tune in this week, here’s one more. Pharmaceutical industry critic and Public Citizen Health Research Group director Sidney Wolfe will be at the conference table, representing the Drug Safety & Risk Management Advisory Committee.

Galson’s Next Career Move: Tobacco Chief?

For former FDA official Steve Galson, the news that CNN medical correspondent Sanjay Gupta has withdrawn from consideration as President Obama’s top choice for Surgeon General means that he still has a job—at least for a little while longer.

Galson, the former director of FDA’s Center for Drug Evaluation & Research, has served as acting Surgeon General since October 2007. Since then, he has kept a relatively low profile, even for his office, which hasn’t had a publicly visible Surgeon General since C. Everett Koop during the Reagan Administration.

Gupta’s star power would have changed all that, but it looks like that’s not in the cards. For Galson, that means holding down the fort a little longer while Team Obama regroups and settles on a backup. When this does all shake out, Galson will have a lot of options—a return to FDA among them—as we’ve blogged in this earlier post.

So we’d like to put forth a suggestion made by one of our intrepid readers: should Congress agree to give FDA regulatory authority over the tobacco industry, who better to head the Center for Tobacco Products than former acting Surgeon General Steven Galson?*

Here’s why: Galson is a former FDA official, so he’s walked that beat before. He is a rear admiral in the Public Health Service, so he’s got that angle covered. He’s worked for the Centers for Disease Control & Prevention, so he knows all about the risks associated with tobacco use. And he’s been at the Environmental Protection Agency—hey, isn’t tobacco an environmental hazard?

We think it’s a brilliant fit, and the timing might work out perfectly. Once a permanent Surgeon General is named, Galson isn’t likely to stick around. While he has said he’d consider a return to FDA, that depends in large part on the inclinations of the expected commissioner nominee, Margaret Hamburg. (Which, despite what you may have read elsewhere, you heard about here first. Just saying.)

Anyway, given that congressional action on tobacco is a foregone conclusion, the Administration will be looking for someone to head up FDA’s oversight. Hamburg may choose to take an active role, given her resume, but she’ll still need someone to head the center. We figure that at about that time, Galson will be looking to make his next career move. What perfect timing!

Naturally, there are a lot of “ifs” in that scenario: if FDA gains the authority to regulate tobacco; if the law clears the legal challenges that are sure to follow; if Galson is offered the job; and if he is willing to accept it. (And if the world hasn’t ended by the time all that happens.)

Given all that, it may not happen. But it sure is fun to think about.

*Not based on fact or rumor; just a career suggestion.

FDA's "Secret" Opioid REMS Meeting

Who doesn’t love to find out about secret meetings? Especially secret meetings between FDA and your top competitors?

Well, if you have any interest in FDA’s implementation of Risk Evaluation & Mitigation Strategies—especially if you market opioids—then you’re in luck. Because we’ve got the scoop on what happened at the closed-door meeting FDA held last week about requiring a class REMS for extended-release pain killers.

FDA holds closed-door sessions with industry all the time. But as we reported in “The Pink Sheet,” this meeting was especially significant: the first in a series of discussions to develop a risk management plan that will be, in the words of one FDA official, “orders of magnitide” greater than anything industry has ever seen.

For the opioids under that umbrella—and those that are not—the REMS will change the commerical landscape for prescription painkillers.

To be fair, it wasn't really a “secret” meeting: FDA announced when was taking place (March 3), and disclosed who was invited (16 opioid manufacturers, listed here). But it also wasn't open to the public, and any information about what happened at the meeting had to be gathered after it took place.

Since we published our story, FDA has released a bit more information, posting the agenda and the slide decks from the three agency presentations on its website. Division of Analgesics, Anesthetics, and Rheumatology Products Director Bob Rappaport gave a history of the risk management of the opioid class; Associate Director for Policy Jane Axelrad reviewed FDA’s REMS authorities under the Amendments Act; and deputy division director Sharon Hertz outlined FDA’s initial thoughts on the proposed REMS.

Right now, FDA wants to see a class Medication Guide; elements to assure safe use (certification of health care providers, physician training on proper use, and patient-physician agreements); and an implementation system (database of all enrolled health care providers and a system to monitor and evaluate the REMS). That could all change, of course, but that is FDA's current thinking.

None of those elements are surprising; they have all been used in past REMS. And as scheduled drugs, opioids already carry some restrictions on their use. But given the sheer size of the market involved, the development and implementation of this REMS should be watched closely.

(Image by flicker user Anna C. used with permission through a creative commons license.)

FDA Commissioner Hamburg

As we've reported to you before, the White House is closing in on naming former New York City Health Commissioner Margaret Hamburg as FDA Commissioner. 

Hamburg is understood to be currently preparing for Senate confirmation hearings. Baltimore Health Commissioner Joshua Sharfstein will reportedly serve as principal deputy commissioner.

To read the full story, click here at The RPM Report.  The announcement could come Monday. 

Whoops! Did We--and Novo--Speak Too Soon?

Did we—and Novo—speak too soon yesterday about Victoza’s chances at the FDA advisory committee next month? We reported Novo’s confidence that its GLP-1 analog liraglutide won’t be required to comply fully with the new FDA diabetes guidance issued last December.

Today, however, Takeda tells us that FDA has said its new diabetes treatment, alogliptin, will indeed be subject to the December guidance, even though it, like Victoza, was submitted earlier. It appears that Takeda will require more data, and, according to JP Morgan analysts, “this provides absolute clarity that FDA will now apply its new guidelines to all new diabetes drug applications.” Oh dear. Misplaced confidence? (Certainly Novo’s investors think so: shares were off about 3% today.)

But Novo’s position hasn’t changed. “Today is no different than yesterday,” Novo’s CMO Mads Krogsgaard Thomsen told The In Vivo Blog this afternoon. Liraglutide’s clinical trial program is more than double the size of alogliptin’s. And they’re completely different drugs: alogliptin is a DPP-IV inhibitor, a class that isn’t shown to improve blood pressure or reduce weight, as Novo claims is the case with Victoza. It’s conceivable, therefore, that FDA might hold DPP-IV inhibitors up to the new guidance—but not GLP-1 analogs, at least, not quite so strictly.

Thomsen also re-iterates that the company has done its MACE analyses (of CV events) with good results—indeed, the JP Morgan analysts appear to interpret this as Victoza actually meeting the new guidance requirements, despite the statistical powering issues (we couldn’t check as they don’t talk to journalists.)

Victoza’s other potential advantage: it’s clearly differentiated from the only other drug in its class, Lilly/Amylin's Byetta, on both efficacy and conveniece. Takeda can’t say the same.

Good for Novo. Why not hold a brave face? If one thing’s clear, though, it’s that victory next month is not a foregone conclusion. But even if Victoza does stumble—and, as one of you kindly pointed out yesterday, pancreatitis is another possible hurdle, given Byetta’s story so far, although Novo doesn’t think it will be more than a labelling issue—Novo might not mind that much (not that it would ever say so.) As mentioned, any delay would likely stall Byetta LAR, too. Which leaves Novo playing in the field where it’s strongest: insulin.

image from flikr user Mel B. used under a creative commons license

Novo Confident of Victoza Victory at FDA in May

The odds might appear to be stacked against it, but Novo Nordisk sounds remarkably confident that GLP-1 analog liraglutide (Victoza) will get approval from FDA by the end of May.

OK, so it needs to be confident: even if it is approved as expected, the once-daily drug, already about four years behind schedule, will have barely a year to make its mark before Lilly/Amylin’s once-weekly version of the incumbent GLP-1 analog Byetta hits the market in 2010.

But Novo’s up against a very diabetes-resistant FDA, with strong memories of the Avandia fallout, that has recently changed its guidelines in this disease area to require more safety data among patients at high risk of cardiovascular disease. And this, as Novo’s CMO Mads Krogsgaard Thomsen acknowledges, is “just the reverse of how we’ve recruited patients into diabetes trials in the past,” including into the liraglutide Phase III trials.

Traditionally, companies have sought to prove their drug’s safety and efficacy in relatively clean patient populations first. Given the cv signal picked up from Avandia well after that drug was approved, it’s clear why the agency has taken a more severe stand.

Among the 6000 or so patients in the liraglutide Phase III trials, very few suffered cv-related events. That’s good for those 6000, but it’s less good as far as providing sufficient statistical power to convince an edgy FDA to wave the drug through. Worse still, since Victoza’s early April advisory committee meeting is widely expected to provide the test case for the new guidance, FDA will be keen to set examples, not make exceptions.

Still, Novo’s got its defense all lined up--and its fingers crossed. For one thing, argues Thomsen, the guidance relates only to drugs that were not submitted by the time it was published, late last year. (Novo submitted liraglutide in May 2008.) There's some controversy over this, but the guidance, as Thomsen underlines, specifically appears to refer to studies in the planning stage and studies completed before submission of the NDA/BLA. (See pages 3 & 4.)

Plus, he adds, "we did not a receive any letter from FDA to say we would have to adhere to the guidelines with liraglutide, as we did for our [Phase II, not-yet-filed] once-weekly GLP-1 analog NN9535." His second point: when looking at risk factors like body weight, systolic blood pressure or biomarkers of cv events, “our data shows nothing concerning at all,” Thomsen told The IN VIVO Blog.

Sure, but FDA could always retort with: “Nor did Avandia’s. That’s the point of our guidance.” At this stage, Novo is hoping that its willingness to do a post-approval study looking specifically at cv outcomes will be enough to win the agency’s favor. “Even though the event numbers are small, we’ve done the [cv event] analyses that the agency asked for--the same ones it will now require going forward--and this convinces us at least why there’s a good case for not requiring a pre-approval study.” He goes on to say that liraglutide may even provide cv benefits.

Favorable trends aren’t enough, though. But whatever hoops Novo has to jump through, its competitors, BMS/AZ and Takeda, both with DPP-IV inhibitors currently under review and, more pertinently, Lilly/Amylin with Byetta LAR, will have to do the same. And whether Novo has to do its CV outcomes trial before or after approval, at least that data will help it make its case in the next—likely even tougher—regulatory challenge it faces with liraglutide: getting it approved for obesity.

image from flickr user samthsham used under a creative commons license.

FDA and Tobacco: Yes, They’re Serious

We’ve been writing for some time now that the new Administration is acting as if giving the Food & Drug Administration the authority to regulate tobacco is a foregone conclusion.

The nomination of Bill Corr (recently of Campaign for Tobacco Free Kids) as deputy secretary of Health & Human Services was a big clue. And so was the emergence of Margaret Hamburg as the expected nominee to head FDA itself.

Each time we mention it, the reaction from our biopharma readers is the same: “You have got to be kidding me.”

The notion of giving FDA the authority to regulate tobacco is “an idiotic idea that is utterly at odds with FDA's mission to protect the public health,” one former industry attorney who has recently joined private practice wrote. “Aren't there enough broken parts at FDA that need fixing now without the distraction of tobacco? Wow.”

That pretty well captures the biopharma industry view. They want FDA to have the leadership and resources to tackle the regulatory mission it already has—without the distraction of building a whole new mission at the same time.

Its time for industry to face facts: Congress and the new Administration are indeed serious about making tobacco regulation part of what FDA does.

How serious?

Wendell Primus, senior policy advisor to Speaker of the House Nancy Pelosi, told Avalere Health’s Diabetes Forum yesterday that a tobacco regulation bill is “next up” for the House.
Not the next FDA item up. Not the next health care item up. Next. Before stem cells, the budget, energy, and health care reform (in that order).

Primus later highlighted tobacco regulation as very much a part of health care reform, in discussing the importance of wellness and prevention as part of that initiative.

The House bill will be marked up today in the House Energy & Commerce Committee, chaired by Henry Waxman who championed FDA’s last efforts to assert regulatory jurisdiction over cigarettes under Commissioner David Kessler. (You can read the Washington Post’s preview here; note that the only objections seem to be from public health advocates who say the measure isn’t tough enough on tobacco companies.)

So, like it or not, expect FDA to have a major new regulatory role in the near future.

Von Eschenbach Maps Out Role In Health Reform

“I’m not going to go fishing and play golf.”

That is how former FDA commissioner Andrew von Eschenbach describes his post-government plans after leaving the Food & Drug Administration: a consulting gig at Greenleaf Health LLC, a return to MD Anderson and any “other opportunities,” should they present themselves. Von Eschenbach left FDA in January when President Barack Obama took office and has kept mum about his future plans.

Until now. On the policy side, von Eschenbach is teaming up with an old FDA colleague—his former chief of staff Patrick Ronan. Von Eschenbach will be a senior adviser at Greenleaf Health, a regulatory consulting firm that Ronan founded upon leaving FDA in 2006. Ronan was von Eschenbach’s chief of staff for his first year on the job, and the two have kept in touch after Ronan left the agency, von Eschenbach said.

Greenleaf’s clients include medical device companies, pharmaceutical manufacturers and public relations firms, but Ronan says Greenleaf’s sweet spot is with smaller biotechs without a Washington presence that need regulatory guidance. Ronan and von Eschenbach are the two principle advisors; Greenleaf also has a chief marketing officer.

Of course, as a former government official, von Eschenbach is restricted in the work he can do as an industry consultant. For the next year, for example, he cannot advocate directly to FDA on behalf of a third party. And he has a lifetime ban on lobbying the agency on the rules and regulations upon which he worked on or influenced while he was commissioner.

But in speaking to von Eschenbach, that doesn’t sound like the type of work he’s interested in anyway. In a phone interview, von Eschenbach talked broadly about “contributing to a more strategic discussion of the future of health care” and helping to find “integrated solutions” for diseases like cancer and Alzheimer’s—all in the context of the greater health reform debate.

As he was at FDA, von Eschenbach is interested in issues like personalized medicine, genomics and informatics, and ways in which the system can prepare for a more patient-centric health care environment. Greenleaf, he says, is a great “launching pad” by which to contribute to those kinds of macro health care issues, and participate in a “greater conversation on a global perspective.”

Von Eschenbach is also “deeply interested” in directly contributing to health reform efforts—one of President Obama's priority issues for his first term. Von Eschenbach says he is open to talking to policymakers (without directly lobbying anyone) about changes that are needed to support the types of products—like personalized medicine and drug-diagnostic combinations—that he believes will be the future of health care. (Von Eshenbach offered thoughts on that topic during a recent health policy conference sponsored by The Atlantic. You can read more in an upcoming issue of The RPM Report.)

If that weren't enough, he's also returning to academia. As we predicted in an earlier blog post, Von Eschenbach is returning to University of Texas MD Anderson Cancer Center in Houston, where he spent 25 years of his career in various leadership positions before being named director of the National Cancer Institute in 2000.

Upon his return to MD Anderson—which is still in the works—he will be an adjunct professor and will serve on the advisory board of the David Koch Center for Applied Research in Genitourinary Cancers. His first board meeting is April 3.