FDA Drug Approvals: Back to the Future

The first two new therapies cleared by FDA in 2011 feel like hail from a bygone era: a serotonin inhibitor antidepressant and an angiotensin II blocking anti-hypertensive. This is certainly not how we expected the new drug approval process to work after the FDA Amendments Act was signed into law in 2007.

Our view of the new drug safety law was that it would favor drugs to treat relatively small, high need populations—and especially ones where robust risk management plans could deliver high value to very sick patients. Primary care blockbuster indications? Not so much.

As we like to put it, it will never be 1997 again.

Or will it?

Take the antidepressant Viibryd (vilazodone) and the angiotensin II receptor blocker Edarbi (azilsartan). Both enter crowded primary care classes that seemed vibrant and innovative 15 years ago, but feel saturated and, well, generic today. And both applications breezed through FDA early in 2011, gaining approval on the first cycle, with no deadline extension and no advisory committee review. Just like they probably would have in 1997.

Heck, when Forest acquired Clinical Data, the manufacturer of Viibryd, it felt even more like turning back the clock, with the company that brought Celexa and then Lexapro to market in the 1990s buying back into the class.

And it isn’t just these two drugs. For all the talk that “me too” drugs are out of favor, there have been other recent examples of "me too" success at FDA. Like, for instance, pitavastatin—a statin!—which cruised through FDA in 2009. Or Watson’s Rapaflo, which breezed through in 2008 to provide yet another alpha blocker option for men with BPH.

Those recent approvals are surprising not just for their nostalgic value. They are remarkable as examples of products making it through the agency at a time of chronically dismal new drug approval statistics. Viibryd and Edarbi cleared FDA amid some fairly prominent disappointments for orphan products (Protalix’ Uplyso gets a complete response; Pharming’s Rhucin gets a refuse to file letter), seemingly tougher standards in oncology (think Avastin and TDM-1), and some setbacks for attempts to repurpose old blockbusters for new indications (Contrave for obesity, for example).

What’s going on here?

Okay, first of all, it isn’t 1997 again.

For one thing, even with the two latest approvals, FDA will be lucky to reach half the total in NME/novel biologics for 2011 that it cleared in 1997. FDA approved 44 new molecules that year, compared to just 21 in 2010, and there is no reason to expect a higher total in 2011. (For a comprehensive look at the pending new products in 2011, check out this week's issue of "The Pink Sheet," here.)

And, while the new drugs are coming into huge classes, they don’t exactly have 1997-level blockbuster expectations. Kowa/Lilly’s launch of pitavastin (Livalo) generated just $5.7 million in sales in 2010. That’s just a few hours worth of Lipitor sales. Forest paid $1.2 billion to acquire Clinical Data and Viibryd. That’s a lot of money—but doesn’t exactly suggest anyone things Viibryd will be a billion dollars a year any time soon.

On the other hand, it’s not like other recent launches are doing so great either. Lilly isn’t getting rich on Livalo, but it isn’t getting very far with Effient either--at much higher cost.
And Effient—despite (or perhaps because of?) a massive dataset including a head-to-head comparative trial—struggled through FDA, requiring a protracted review and a public airing of safety questions at an advisory committee, followed by still more internal wrangling over whether and how to address those questions.

Compare that to Edarbi, which went through FDA in 10 months without any public hiccups--and with head-to-head superiority data versus the market leader. It didn’t need an advisory committee, because—as FDA explains in the approval letter—

“This drug is not the first in its class, the safety profile is similar to that of other drugs approved for this indication, the clinical study design is acceptable and similar to previously approved products in the class, evaluation of the safety data [when used in the treatment of hypertension] did not raise significant safety or efficacy issues that were unexpected for a drug of this class, the application did not raise significant public health questions on the role of the drug in the diagnosis, cure, mitigation, treatment, or prevention of a disease, and outside expertise was not necessary; there were no controversial issues that would benefit from advisory committee discussion.”

That may not sound like a ringing endorsement of the products therapeutic potential, but at today’s FDA lack of controversy might be as good as it gets. Commercial models aside, it is just possible that the secret to a first cycle, on time approval is as simple as “me too.”

Onglyza and the Type 2 Diabetes Approval Path: The Map is Still Sketchy

Biopharma companies hoping to develop drugs to compete in the type 2 diabetes market can breathe a bit easier with the approval of Bristol-Myers Squibb/AstraZeneca’s Onglyza (saxagliptin): the final go ahead from the Food & Drug Administration July 31 unequivocally shows that it is indeed possible to meet FDA’s new cardiovascular safety guidelines for the class.

The outcome is not surprising, after an advisory committee overwhelmingly supported approval of the drug earlier this year—but given the delays and uncertainty, sponsors may be forgiven if they weren’t going to believe it until they saw it.

And now that FDA has posted the approval letter for the drug, sponsors can get to work on figuring out exactly what it will take in terms of post-marketing requirements in the type 2 market of the future.

The letter makes one thing clear: a mandatory Risk Evaluation & Mitigation Strategy will not be an inevitable price for entering the class. Onglyza was approved with a host of post-marketing study commitments, but no REMS.

As for those post-marketing studies themselves, the key commitment is exactly what sponsors would have expected: a prospective clinical trial to assess cardiovascular outcomes. That section is bound to be read carefully by sponsors eager for more clues about how onerous post-marketing trials will be in the class. But they probably won’t learn much that they don’t already know.

Recall that during the advisory committee, Bristol declared its intention to run a study to demonstrate a superior cardiovascular safety profile for saxagliptin. The approval letter (in keeping with the safety focus of the new post-marketing authorities) frames the trial differently, with the goal of showing a relative risk of 1.3 or less versus the control population.

The letter also does not include any details about numbers of patients, duration of therapy or other key trial design elements. However, FDA has made clear its preference for an event-driven trial design, which (assuming Bristol agrees) would make some of the those elements irrelevant.

The letter does detail a number of other specific risks to test for (most triggered by signals in the NDA for Onglyza, but some clearly of a classwide concern.)

And it does set some deadlines. Bristol must finish designing the trial in November, and then complete the study in less than five years.

But beyond that, there’s not much to learn.

Still, the Onglyza letter is certain to be a template for future approvals in the type 2 diabetes class, so here is how FDA describes the pivotal post-marketing trial:

"A randomized, double-blind, controlled trial evaluating the effect of saxagliptin on the incidence of major adverse cardiovascular events in patients with type 2 diabetes mellitus.

The primary objective of this trial is to establish that the upper bound of the 2-sided 95% confidence interval for the estimated risk ratio comparing the incidence of major adverse cardiovascular events observed with saxagliptin to that observed in the control group is less than 1.3.

Secondary objectives must include an assessment of the long-term effects of saxagliptin on lymphocyte counts, infections, hypersensitivity reactions, liver, bone fracture, pancreatitis, skin reactions, and renal safety. For hypersensitivity reactions, especially angioedema, reports should include detailed information on concomitant use of an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker. For cases of pancreatitis, serum amylase and/or lipase concentrations with accompanying normal ranges and any imaging study reports should be included in the narratives.

Because renal impairment is an important complication of diabetes, you must ensure that there is a minimum of 1 year of exposure for at least 200 saxagliptin-treated patients with moderate renal impairment and at least 100 saxagliptin-treated patients with severe renal impairment.

The timetable you submitted on July 15, 2009, states that you will conduct this trial according to the following timetable:

Final Protocol Submission: by November 30, 2009


Study Completion: by July 31, 2015


Final Report Submission: by January 31, 2016.”

Sharfstein Speaks: Is He Headed To Washington?

During a Baltimore City rally for Barack Obama on Saturday, Dan Rodricks, a host for the local National Public Radio station, WYPR, got a coveted interview with a Baltimore official who has been making national headlines.

No, it wasn’t Baltimore City mayor, Sheila Dixon, who was recently indicted for perjury and theft charges (and who, may we add, did not receive a shout-out from president-elect Obama when he addressed the massive crowd).

WYPR spoke to Baltimore City health commissioner Joshua Sharfstein, one of two finalists for the FDA commissioner job. (You can read all about that story in this week’s issue of “The Pink Sheet.”) Sharfstein was at the Obama rally in an official capacity as health commissioner, directing people to warming tents and trying to prevent hypothermia and frostbite.

And while that's certainly a good story, Rodricks also asked Sharfstein whether he would leaving Baltimore to become FDA commissioner. Sharfstein was non-committal (as would be expected), but also expressed his deep admiration for Obama, and the science-based policies that he will support as president.

We’ll let you be the judge on the meaning behind his remarks. Here’s the interview, as transcribed by us from an online recording of Dan’s show, which aired yesterday afternoon:

Dan Rodricks: Are you going to go to work in Washington? Are we going to lose you here in Baltimore?

Joshua Sharfstein: I’m fully expecting to be health commissioner of Baltimore. It’s a great job, and lots to do this year.

Rodricks: OK, because there have been all these stories in the press about Joshua Sharfstein and the Food and Drug Administration.

Sharfstein: I know, my mom sends them all to me.

Rodricks: But you’re going to be around here for a while?

Sharfstein: That’s what I totally expect.

Rodricks: What do you expect from Barack Obama….Are you expecting generally more progressive ideas coming out of the White House?

Sharfstein: Absolutely. The first thing he said is that he wants to base health policy on the science. That’s a huge shift from what we’ve had. When you look at the science, you look at what things have worked, those are the kinds of things that we’re trying to do in Baltimore. I think we can expect some support for that, because we’ve got evidence for what we are doing. ...

Rodricks: Have you felt this way before about a president?

Sharfstein: I’ve never experienced anything like this. It’s been terrific. I’ve had a chance to work on the transition some, and that’s been great. From the moment—I just remember Iowa and everything, it’s just been so exciting.

Photo credit: Reuters/Jason Reed

FDA Commissioner Update

It looks as if the Race to White Oak is almost over. We know at least one commissioner candidate was informed of the decision yesterday.

As we said previously, a decision was likely to be made yesterday with an announcement coming later this week or soon thereafter. To read our previous post, click here.

We also understand that David Dorsey could be named FDA Chief Counsel and Bill Schultz could be named HHS General Counsel. Both picks would make a lot of sense.

Dorsey previously worked in the FDA Office of the Chief Counsel before leaving temporarily to join the staff of Senate Health, Education, Labor and Pensions Committee Chairman Ted Kennedy. Dorsey returned to the agency last week.

Schultz, if named HHS General Counsel, would be the second former staffer of House Energy & Commerce Chairman Henry Waxman to ascend to a top position in the health department. Schultz previously served as counsel to Waxman on food and health care issues.

He was also deputy commissioner for policy at FDA and a former assistant deputy attorney general. Schultz most recently involved in negotiations over an abbreviated approval pathway for follow-on biologics. As a partner with Zuckerman Spaeder, he was one of four principal negotiators of compromise legislation and represented the generic drug industry in those talks. To read our coverage of FOBs, click here.

Dorsey was also heavily involved in the FOBs negotiations on the Senate side as a staffer to Kennedy.

We'll let you know when we find out more.

Corr Returns to HHS: Another Piece in FOBs Puzzle

Bill Corr will be Health & Human Services Secretary-designate Tom Daschle’s deputy secretary.

The position requires Senate confirmation. Corr has been an advocate of tougher government controls on tobacco, which often draws the ire of some Republicans in the Senate. As a long-time aide to key Democratic health figures on Capitol Hill (including Daschle), however, Corr’s confirmation is a formality.

In addition to working as chief counsel and policy director for Daschle for two years, Corr has valuable experience within the HHS bureaucracy, acting as an advisor and chief of staff to Clinton Administration HHS Secretary Donna Shalala. He has also been a leader of the Obama HHS transition team, catching up on the broad array of current initiatives.

From biopharma’s perspective, the most important quality that Corr brings to the new position is a familiarity and commitment to an approval pathway for follow-on biologics. Corr was Congressman Henry Waxman’s (D-Calif.) primary staffer for the Waxman-Hatch generic drug law in 1984.

Corr was a forceful advocate for establishing a clear route for quick approval of generics at the end of patent terms as a way to cut drug prices and reduce drug marketing activities – in a period when drug marketing was a pale version of the current level of promotional support.
In fact, despite the rapid success of the Waxman/Hatch legislation in creating a generics drug business, Corr was not pleased by the ability of the program to bring down drug prices rapidly.

He held a hearing two years after the enactment of the law to show that drug companies were still charging high prices. That hearing also showed the unanticipated effect of driving companies to expand dramatically their research budgets (from 8% of sales to around 12-15% of sales) to try to find products to replace products facing generic competition.

Corr won’t be able to devote the same type of focused attention to the development of follow-on biologics legislation, but he will be able to press FDA for action and he won’t need a long-time to learn the ins-and-outs of the issues. There won’t be long delays trying to discuss the philosophy of follow-on biologics at the top level of HHS.

Corr’s appointment may affect the FDA selection process in a variety of ways.
From his Congressional background, Corr shares the most with Josh Sharfstein (head of the Baltimore Health Department). They both served Waxman, though in distinctly different generations: Corr in the late 1970’s and early 1980’s and Sharfstein recently. That connection, however, could cut both ways. There may be subtle reaction against putting too many people recognized as disciples of Waxman in key positions throughout HHS. FDA watchers have already begun speculating that Sharfstein’s candidacy is losing momentum.

By temperament, Corr is closer to the Cleveland Clinic’s Steven Nissen.

Through his commitment to anti-tobacco campaigns, Corr shares a common theme with former FDA Commissioner David Kessler.

Frank Torti Tapped As Acting FDA Commissioner

Drum roll, please….The next commissioner of the Food & Drug Administration will be chief scientist and principal deputy commissioner Frank Torti.

According to an email message sent to HHS staff on Friday evening, Torti will become acting FDA commissioner come Inauguration Day, once Andrew von Eschenbach leaves office. Torti will serve under President Barack Obama until a permanent successor is named.

The announcement comes more than a week before the transition will take place. After 300 meetings with department and agency staff, HHS chief of staff Rich McKeown said in the email message, “the next phase of Transition involves the departure of our team on January 20, and the arrival of President-Elect Obama’s team later that day.”

“In order to create a clear path for leadership transition, I am attaching a list of senior leaders who will become the acting heads of their respective agencies and offices (or in some cases, remain as heads of their respective agencies and offices) until the new Administration appoints individuals to various leadership positions.”

HHS secretary Michael Leavitt will leave the department once President-elect Obama takes office. Assistant secretary Charlie Johnson will lead the department until Secretary-designate Tom Daschle is sworn in. “Once Secretary-designate Daschle is confirmed by the Senate and sworn in as HHS Secretary, he will assume leadership of HHS,” McKeown’s email says.

Once that happens, Daschle is expected to quickly announce his picks for the heads of each agency. At his Senate confirmation hearing last week, Daschle said that the Obama transition team had been aggressively interviewing candidates, and that he hoped to start building his new leadership within the next few weeks. (We've filled up the ethernet with quite a bit about potential commissioner candidates; you can start here, here and here).

But at least for now, Torti will be The Man at FDA. So what do we know about him? If you attended FDC-Windhover’s FDA/CMS Summit for BioPharma Executives in December, then you heard his keynote address first-hand. But if you missed it, you can check out this story from “The Pink Sheet.”

But we can’t help but point out that we called this one back in June—despite rumblings from Torti’s colleagues at Wake Forest that he would be returning to academia as soon as the next president took office.

In many ways, Torti is the logical pick: under the Federal Vacancies Act, Torti’s position as principal deputy commissioner puts him in line to become acting commissioner once von Eschenbach departs. Having joined the agency less than a year ago, he carries no baggage. And he comes from an academic (not political) background—the perfect profile for a caretaker commissioner.

But as recently as early December, Torti had not yet been approached about the job—at least not to the point, he said, where he would have to sit down with his wife and discuss a longer stay in Washington than was originally planned. But, hey, a lot can happen in a month.

Here are some of the other top-level acting positions announced by HHS:

The Centers for Medicare & Medicaid Services will be headed by chief operating officer Charlene Frizzera; acting CMS administrator Kerry Weems will step down;

The Centers for Disease Control & Prevention will be led by chief operating officer William Gimson; current director Julie Gerberding will leave office;

The National Institutes of Health will continue to be led by acting director Raynard Kington;

The Agency for Healthcare Research & Quality will continue to be headed by director Carolyn Clancy; and

The Office of the Surgeon General will continue to be held in an acting capacity by Steven Galson (more on his future plans here).

Gupta in for Galson: What's Next for Former FDAer?

Anyone looking at the FDA public calendar this week (who doesn’t love to keep track of the comings and goings of government officials?) may have noticed something peculiar: Steven Galson, the former director of the Center for Drugs, was listed as an FDA participant in a recent meeting at the agency.

According to FDA’s website, Galson joined FDA commissioner Andrew von Eschenbach and Center for Drug Evaluation & Research director Janet Woodcock at a “meet and greet” with the University of Florida officials at FDA’s Silver Spring headquarters on December 17. Galson and Woodcock are listed as “other FDA participants.”

There are a lot of changes expected in FDA leadership in the next few weeks, but Steve Galson’s return to the agency was not one of them. So naturally, we were a bit curious. Could Galson, who left CDER in October 2007 to become acting US Surgeon General, be returning to FDA? Or did the agency’s webmaster err in including him on the calendar?

We reached out to Galson to ask him to explain. It turns out he was invited to participate in the closure of an agreement between FDA and the University of Florida on a new fellowship program. That program, which is designed to bring fresh blood into FDA, is a pet project of von Eschenbach’s and one that his principle deputy commissioner, Frank Torti, has been overseeing since joining FDA last summer.

Galson was invited not in his capacity of a former FDA official (despite what the public calendar says), but because the Florida deal involves officers in the Public Health Service, and as acting Surgeon General, Galson is the Commander of the Commissioned Corps. (He’s also a Rear Admiral.)

But that doesn’t necessarily mean that a return to FDA isn’t in the cards. Galson is expecting to be out of a job in the next few months: according to the Washington Post, President-elect Barack Obama has offered the Surgeon General position to prominent neurosurgeon and television talking head Sanjay Gupta.

Galson is a career government official—not a presidential appointee—so he's not expected to be immediately asked leave the Surgeon General’s office once Obama takes office. But with Gupta as the apparent pick as his successor, it looks like Galson will be looking for another job in the next few months. So what’s next for the former FDA official?

Galson says “is not ruling out any possibilities”—including a potential return to FDA. His next move, Galson says, will depend on how certain appointments come out (presumably the FDA commissioner spot), but he's “looking at all options.”

We’re sure Galson has lots of options—in addition to FDA, he has held senior-level positions at the Environmental Protection Agency (as head of the Office of Science Coordination & Policy) and Department of Energy (as chief medical officer) and worked earlier in his career at the Center for Disease Control and Prevention.

But Galson did join FDA specifically to help the agency revamp its postmarketing surveillance program. That was in 2001, and the agency is still revamping its postmarketing surveillance program. We're just speculating here, but maybe that “meet and greet” at FDA will be the start of Galson's next career move.

Next Steps For Prasugrel: The Anatomy of an Advisory Committee

Eli Lilly and Daiichi Sankyo used the morning of New Years Eve (‘tis the season for hiding news) to announce that the delayed anti-clotting drug prasugrel will be considered by the Cardiovascular-Renal Advisory Committee February 3. (Shameless self-promotion alert: We predicted that February meeting in October.)

Now that a date has been offically set, let the next round of speculation begin.

That news can be viewed in two ways: optimists (like Lilly and Daiichi investors) will argue that the meeting is a signal that the review is wrapping up and a decision is close at hand. Pessimists will argue that the meeting is an indication of the internal strife at FDA over prasugrel’s benefit-risk profile—and that products that go before an advisory committee are less likely to be approved on the first cycle.

Here's our take. First, we should note that the confirmation of the advisory committee meeting is a milestone in prasugrel’s development. It’s the first word to come out of FDA on the drug since June, when the agency extended the review by three months. FDA then let the revised September 26 review deadline pass without an approvability decision.

Another positive indicator for Lilly and Daiichi is that FDA is only convening the Cardio-Renal committee—and is not asking for a joint review with the Drug Safety & Risk Management Advisory Committee. A joint meeting would indicate significant concerns at FDA regarding prasugrel’s safety profile, which we have delved into in this earlier post.

Of course, that certainly doesn’t preclude FDA from drawing from members of the Drug Safety & Risk Management Advisory Committee as needed—including its newest member, Public Citizen’s Sidney Wolfe, who is unlikely to look kindly upon the prasugrel NDA.

Wolfe is just one extra member that could be asked to show up on February 3, given the current vacancies on the Cardio-Renal advisory committee. There are just eight permanent Cardio-Renal members, including a consumer rep (Consumers Union’s Stephen Findlay) and a non-voting industry rep (AstraZeneca’s Jonathan Fox).

That can make for a lot of last-minute additions. At the committee’s last meeting, FDA added 13 temporary members, including two regulars: University of Washington statistician Thomas Fleming and Duke University human cognition expert Ruth Day.

So who might be asked to serve? With a product like prasugrel, one obvious choice for a temporary member is Steven Nissen, the head of cardiology at the Cleveland Clinic—an expert on cardiovascular drug safety and a former chair of the Cardio-Renal advisory committee.

Nissen’s participation on the committee would be a positive development for Lilly and Daiichi, given that he has come out in favor of prasugrel—first giving the drug a thumbs up for approval and then criticizing FDA for not delivering an on-time approvability decision. Nissen isn’t exactly a shrinking violet, so if he still favors a prasugrel approval, he stands a good chance of getting the committee to see things his way.

But those statements may prevent Nissen from serving—especially given FDA’s tougher line on conflicts of interest. Indeed, Nissen himself has questioned whether he is qualified to serve on an advisory committee under the new CoI guidelines. The meeting roster will be out in the next month. Lilly and Daiichi should hope Nissen's name is on it.

Human brain image courtsey of flickr user hduhadaway.

Lilly's Prasugrel Widens the Gap

The gap just got wider.

No, we’re not talking about the income inequality gap, or the gender gap, or the generation gap. We’re talking about the approval gap for new drugs and biologics between Europe and the United States.

Some critics of the Food & Drug Administration argue that FDA is more conservative than its counterparts in Europe. (This is what we think of as the “too slow” contingent. FDA is also criticized from other stakeholders—like Sid Wolfe and Chuck Grassley—of being too fast.)

FDA disagrees with both sides. As Office of New Drugs director John Jenkins said at FDC-Windhover’s FDA/CMS Summit for BioPharma Executives, “We review each application on its own merits—not against some goal that we will approve 25 applications this year. Those that meet the standards under the statute get approved; those that don’t, don’t get approved.”

But with last Thursday’s news that prasugrel—Eli Lilly and Daiichi Sankyo’s beleaguered blood thinner candidate that is still sitting at FDA—received a positive recommendation from the European Union’s Committee for Medicinal Products for Human Use, the noise from the “too slow” contingent is likely to get louder.

In an effort to discredit those critics, Jenkins presented data at the FDA/CMS Summit from a preliminary analysis of new molecular entities reviewed by FDA and the European Medicines Agency between January 2006 and October 2008. What Jenkins found was that EMEA approved slightly more novel products than FDA, but that the agencies had a similar approval rate.

Jenkins then looked at new molecular entities that were reviewed by both the Food & Drug Administration. Of those 29 products, FDA approved two that the European Medicines Agency has not, and EMEA approved seven that FDA has not. (Once Lilly and Daiichi receive final approval from the European Commission—which should come in two or three months—prasugrel would make that eight.)

Jenkins argued that the numbers are too small to support any conclusions that FDA is more conservative than its counterparts in Europe—especially given that one of the EMEA-approved drugs (Sanofi-Aventis’ weight loss drug rimonabant) has already been withdrawn from the market.

Pointing to the list, Jenkins said: “Here’s where all the statements about the EMEA being faster are coming from.” But some investors still see the data as a troubling trend. The prasugrel approval in Europe is only likely to feed those beliefs. (You can read all about that debate in the latest issue of The RPM Report.)

So what's up with prasugrel at FDA?

As we’ve reported, FDA is looking at February 2009 for an advisory committee meeting. Assuming that happens, an answer isn’t likely much before March 2009—which would double prasugrel's review time to 12 months. The user fee deadline was initially set for March 2008, but on two occasions was pushed back three months—most recently to September. Since then, it has become just one of a number of missed deadlines at FDA.

Cleveland Clinic cardiologist Steve Nissen, who has accused FDA of being both too fast and too slow, thinks Lilly and Daiichi deserve an answer one way or the other. What do you think? Is FDA more conservative than EMEA? Or is the difference too small to draw any conclusions?

Photo courtesy of flickr user StevenBulman44.

FDA Drug Safety Official Seligman Set to Depart

FDA's top drug safety communication official--Center for Drug Evaluation & Research Associate Director of Safety Policy and Communication Paul Seligman--will apparently be moving to a new position focusing on food supply integrity issues.

Seligman is understood to be departing CDER to focus on food quality being imported from Latin America.

Seligman’s departure will leave a void in the safety communication area at FDA’s Center for Drug Evaluation & Research at a critical time for the agency.

FDA is just beginning to get its arms around implementing the many postmarket surveillance provisions of the FDA Amendments Act, including the Risk Evaluation & Mitigation Strategies (REMS), a new requirement for quarterly web postings of emerging drug safety signals and the evolving Sentinel active surveillance system (See “Communication Conundrum,” The RPM Report, October 2008).

Seligman was named associate director of safety policy and communication in April 2006, a newly created position at the time that reported directly to the CDER director. He was previously director of the Office of Pharmacoepidemiology & Surveillance, which was eliminated.

The associate director position was an important organizational change for CDER when first announced because it demonstrated the center’s focus on safety.

Seligman’s primary role was to develop drug safety policies across CDER and oversee the MedWatch voluntary adverse event reporting system, the Drug Safety Oversight Board, the “early communication” program, the drug safety newsletter, and the quarterly safety signal web postings mandated by FDAAA.

Andyisms: A Tribute to Von Eschenbach

In an email to employees this week, FDA commissioner Andrew von Eschenbach announced his resignation from the agency, effective January 20. (Read our take on Andy’s tenure in “The Pink Sheet” DAILY.)

Von Eschenbach joined FDA from the National Cancer Institute in December 2005 as an unflappable, avuncular researcher and cancer survivor who loved to espouse on the future of personalized medicine and the promise of the Critical Path Initiative.

Many of his speeches implored FDA stakeholders to accept and embrace change, usually expressed through one of a collection of metaphors he pulled out for public appearances. And so, to mark his departure from FDA a month from now, we’ve assembled a few of his classics over the past three years. Enjoy.

The Racecar Metaphor:

“One of the rigors of FDA is zero tolerance....I have asked people, do you know how a Formula 1 car can go 200 miles an hour and not kill anybody? Zero tolerance. Everything has to be disciplined and precise—every 'i' dotted, every 't' crossed. But the reason for that rigor and discipline is so the car goes faster, not slower.”

The Typhoon Metaphor:

“To find these moments of change where the change that occurs in that trajectory that the organization is on is not a wind or breeze of change, but a typhoon of change—a strategic inflection in which the change process is magnified in orders of magnitude. And when that kind of change occurs...those that grasp it can then capitalize on it experience exponential growth, and those who don’t understand it, go on to extinction.”

The Hurricane Metaphor:

“There’s a hurricane in the Gulf of Mexico, and since I happen to live in Houston, I think I better pay attention to that, as opposed to, just a little disturbance somewhere.”

The Dirty Diaper Metaphor:

“Creating that future will require change, which will affect all of us, regardless of our role or job title. Unfortunately, the only human organism who actually likes change is a six-month old with a dirty diaper. For most of us, change is what we expect in others.”

The Bridge Metaphor:

“Today we come together as heads of medical product regulatory agencies with the opportunity to collaboratively build a bridge, not a barrier. A bridge that will span the gap between all that promise of science and technology and the delivery of the interventions that can eradicate disease for all of our people. But the bridge must be morphed to accommodate the new science and technology.”

The Locker Room Metaphor, as paraphrased by Sen. Chuck Grassley in a March 12 letter to von Eschenbach:

“I understand that you told the assembled staff that it was important to be ‘a team player’ and that if someone disagreed with the coach, they should keep their opinions and concerns ‘inside the locker room.’ You also said, according to those present, that anyone who spoke ‘outside the locker room’ might find themselves ‘kicked off the team.’”

And finally, our personal favorite: The Butterfly Metaphor:

“In the last decade or two, we have been able to approach disease at the molecular level, where we now can observe and understand disease as a process. This is what I have called the ‘molecular metamorphosis in medicine,’ because it represents a phase change similar to the transformation of a caterpillar to a butterfly. As a result of this metamorphosis, the future of health care will be no more like its past than a butterfly is like a caterpillar.”

Goodbye, Andy. And good luck.

The Lesser Of Two Evils?

When Steve Nissen is not qualified to serve on an FDA advisory committee under the agency’s new conflict of interest guidelines, you know things are bad. Really bad.

According to Nissen, and as reported in "The Pink Sheet" DAILY, his position as chair of the cardiology department at the Cleveland Clinic likely bars him from serving another term on an FDA expert panel.

Nissen may not be exactly beloved by the pharmaceutical industry, but no one can argue that the man knows drug development, and is a global expert on cardiovascular drug safety. And when it comes to conflicts, Nissen prides himself in not only disclosing all the companies he has worked for, but also donating all his fees directly to charities so that he can't claim the tax benefit.

Plus, he has served as an advisory committee member before: Nissen was a permanent member of the Cardiovascular & Renal Advisory Committee from 2001 to 2005, that last year as chairman. Since then, he has served as a temporary member as duty calls, like the July meeting on type 2 diabetes clinical trial endpoints. So if he can't serve, then who can?

“The current rules are pretty bizarre,” Nissen told attendees at the recent FDC-Windhover FDA/CMS Summit. “The imputation of conflict of interest guidelines based on institutional contracts eliminates a lot of desirable people.”

In Nissen’s case, the trouble is with a section of the new CoI guidelines that bars the “head of a department” that is conducting or will conduct studies on a product (or its competitors) “that is the focus of a meeting and receives personnel or salary support, designs or advises on any aspect of clinical trials, or reviews data or reports from the trials.”

We emailed Nissen to clarify, and he pointed out that the cardiology department has more than 100 faculty members. So “for most advisory committees, it is highly likely that someone within our department is involved with the company in some fashion.” And given the size of the Cleveland Clinic, Nissen said, “the likelihood that someone...receives funding from the sponsor or its competitors is 100%.”

Of course, Nissen’s inability to serve on an advisory committee is most likely be welcome news for drug sponsors, who see him as, frankly, a pain in the derriere. Granted, this is the man who prevented Bristol/Merck’s Pargluva (muraglitazar) from ever seeing the light of day, and crippled the commercial future for GlaxoSmithKline’s Avandia. So you can understand that angst.

But industry should not be breaking out the champagne quite yet. If it is true that Nissen is no longer eligible to serve on an advisory committee, it underlines a disturbing trend at the agency: FDA’s continued inability to fully staff its expert panels with individuals that qualify under—and are willing to serve despite of—more stringent conflict of interest guidelines.

When we last looked at the staffing problems in the advisory committee system in The RPM Report, there were 83 vacant seats, and three-quarters of the panels did not have permanent chairs. That was despite a major recruitment effort at the agency. Things haven’t improved much since.

And when drug sponsors start to see who is qualified to serve as permanent advisory committee members under FDA’s conflict of interest rules, they may be wishing for Nissen. You tell us. As a sponsor, who would you rather have: Nissen, or Public Citizen’s Sidney Wolfe and Center for Science in the Public Interest’s Merrill Goozner?

The Long Campaign for FDA Commissioner (Part 3)

We’ve given you some of our thoughts on the candidates for FDA commissioner in the new Administration in several recent posts (here and here). Today, though, we tackle a bigger question: Why would anyone possibly want this job?

For a position that may well be the most thankless job in health care, an awful lot of people seem to be lining up to be the next commissioner of FDA.

With all the problems at FDA right now—a deeply underfunded agency with a nearly impossible mandate to protect the nation’s food and drug supply—it’s a wonder anyone would want to lead the agency. Add the prospect of contentious Senate confirmation hearings, a low public opinion of FDA, and a constant threat of whistleblowers, and you don’t exactly have your dream job.

But that hasn’t prevented people from wanting to be the next FDA commissioner. While much of the campaigning is taking place behind closed doors, some candidates are choosing to be a bit more vocal. Those individuals tend to fall into two categories; the Peter Rost Category of Candidates and the Steve Nissen/David Kessler Category of Candidates.

On one extreme end of the campaigning spectrum, there’s former Pharmacia marketing executive Peter Rost. As the Pfizer whistleblower over off-label promotion of the human growth hormone Genotropin, Rost is probably the one commissioner candidate that scares the bejesus out of pharma (or at least Pfizer) more than Nissen. Or he would if he had any chance of actually landing the job.

Not only is Rost openly campaigning, he is, in his words, “running” for FDA commissioner as though it’s an open Senate seat. Rost’s personal blog is now dedicated to his campaign run, and he has successfully solicited letters of endorsement from Sen. Sherrod Brown (D-Ohio) and Rep. JoAnn Emerson (R-Mo.).

On the other end of the spectrum, we’ll cite David Kessler. Kessler isn’t sending out press releases expressing his interest in the commissioner post, but he is indicating he’d be open to the job through public appearances. As we reported in an earlier blog post, when asked for his ideal profile for an FDA commissioner, Kessler essentially described himself.

The same goes for Nissen. While Nissen may be the last thing that anyone in industry wants in an FDA commissioner, he is laying out an agenda that sounds quite reasonable: more money for FDA, an end to the missed user fee deadlines, and restoring integrity to the agency. Indeed, we laid out in an earlier post why we think FDA commissioner Nissen wouldn't be the worst thing that ever happen to industry.

But even Nissen recognizes the challenges facing the next commissioner, and has publicly questioned whether anyone would want the job. Here’s what he said at FDC-Windhover’s FDA/CMS Summit last week:

“The problem is in the current environment, getting anybody confirmed looks like it could be really tough. You know what the last bunch of commissioners have gone through. You have to be a masochist to want to do that, and there aren’t a lot of people who would want to do that.”

Of course, in saying someone would have to be a masochist to want the job, Nissen didn’t mention whether he was a masochist. Knowing what we know about Nissen, we'd have to say yes.

image via run100miles.com. nothing particularly masochistic about that, eh?

Deal of the Year Nominee: FDA Makes Amgen An Offer It Can’t Refuse

Ah, awards season. Why should film critics have all the fun? And voting! It's not just for presidential elections. This year your IN VIVO Blog team is nominating a handful of alliances, acquisitions, financings, regulatory negotiations and legislative compromises in our First Annual DOTY competition. And then you, dear readers, will vote (early and often, we hope) for the winner. Imaginary federal and international biopharmaceutical statutes prohibit us from awarding a monetary prize. But our winners, when they die, on their deathbeds, they will receive total consciousness. So they've got that going for them, which is nice.

Who said the Deal of the Year has to be a business development transaction between two companies? (Ed. note: nobody!)

At a time when regulatory challenges, reimbursement hurdles and the general political climate is at the top of mind for many biopharma executives and their investors, we think there is a strong argument that the most important deals being struck as 2009 dawns are between industry and government.

And if you are looking for a negotiated agreement involving two or more parties with profound implications for the entire biopharma sector, we think the relabeling of Amgen’s darbepoetin Aranesp and Johnson & Johnson’s competing epoetin brand Procrit more than qualifies. Why this change among all the other labeling changes in the year of “Safety First” at the Food & Drug Administration? Because this was an especially one-sided deal.

The Aranesp relabeling was the the first (and, so far, only) time FDA has used its new power to order sponsors to make specific labeling to changes. FDA gained that with the enactment of the FDA Amendments Act in 2007. So far, the agency has invoked the mandatory labeling authority seven times, but in each of the other cases the sponsor (or sponsors) has agreed to the change. But not with Aranesp.

Talk about an important precedent.

Labeling “negotiations” have always been something of a misnomer, since—from industry’s perspective—it was never exactly a level playing field. Still, at least in theory, manufacturers wrote the label, and FDA approved it. True, when the agency wanted, it could essentially write new labeling by declining any alternative language—but only at the cost of leaving an existing label in force while “negotiations” continued.

The FDA Amendments Act changes all that, giving FDA for the first time the explicit authority to dictate labeling to a sponsor in response to a safety issue.

And with Aranesp, we have the first case study of what FDA can do with that enhanced leverage.

On July 30, FDA announced updated safety labeling for Aranesp to resolve concerns about potential tumor promoting effects of the agent. The agency insisted on two specific provisions that Amgen disagreed with: one restricting use of the products to cancer patients undergoing chemotherapy where a cure is not the expected outcome; the second warning against use when hemoglobin levels are above 10.

What does the FDA action mean? We answer that question at length in an article just published in The RPM Report.

But here are two ways to consider the impact. First, $3 million a week. That is how much Amgen estimates the new restrictions have pinched sales. And remember, this is after an already sharp reduction in the size of the brand after a restrictive coverage policy implemented by the Medicare program. (For a detailed breakdown of the, um, breakdown in Aranesp sales, see the chart below.)


Second, $30 million a week. That is how much Aranesp still generates in revenues—a number that could be much lower if FDA had demanded the withdrawal of the oncology indication altogether (or, even, withdrawal of the product itself.) Before FDAAA, those might have been the only alternatives for FDA. And remember, that is the promise of the new law: FDA has much more authority to dictate who can actually use a drug, but--in theory at least--more drugs make it to market, and those that make it stay.

Coincidentally or otherwise, new drug approvals are up this year, but it is obviously far too early to draw conclusions about how this bargain will actually work out. But one conclusion is clear: labeling negotiations will never be the same...

[Deals of the Year 2009 Bonus Preview: FDA and Amgen are still working out the details of a formal Risk Evaluation & Mitigation Strategy for Aranesp. The agency has already used that authority on several other products, but the Aranesp program must be a doozy: Amgen says it will prompt another 10%-20% drop in sales.]

FDA's Internal Advisory Committee Meetings

Avandia. Vioxx. Ketek. Elidel. Palladone.

What do those drugs have in common? The obvious answer is that they are all associated with a major safety problem that resulted in a significant FDA regulatory action—either a “black box” warning in product labeling, or, in the case of Palladone and Vioxx, outright removal from the market.

But they have something else in common as well. In the months preceding those major regulatory steps, each product was the subject of a relatively unknown internal meeting at the Food & Drug Administration: a regulatory briefing.

Regulatory briefings can be described as “internal advisory committees” at FDA—a chance for review divisions to ask others in CDER for advice on how to handle a tricky regulatory or scientific decision. (For more on regulatory briefings, check out our coverage in The RPM Report. If you’re not a subscriber, you can sign up for a free trial to view the article.)

If you’ve never heard of a regulatory briefing, you’re not alone. Regulatory briefings have been kicking around FDA’s Center for Drug Evaluation & Research for more than a decade, but because they are closed to industry—and review divisions don’t always inform sponsors when one is held—many companies are unaware that they exist. But now FDA is holding more of them, as many as one per week. And they are quite popular with reviewers.

The good news for drug sponsors is that regulatory briefings are not intended to be decisional meetings; the final approvability decision remains with the review division after the meeting is over. But given the typical attendance list—John Jenkins, Janet Woodcock, Bob Temple, Doug Throckmorton and 50-100 other drug reviewers—it would be hard to ignore any advice.

A drug does not have to rise to the level of an Avandia or a Vioxx to be discussed during a regulatory briefing—given the frequency of such meetings, that could not possibly be the case. But, as the list above indicates, they do tend to skew toward the more problematic end of the continuum. The need for a regulatory briefings should not spell doom and gloom for a sponsor, but it could be an indication that something is wrong. That alone makes them worth watching.

image via FDA

Nearing an End to the Longest Review?

Ovation reached a milestone this month in its quest to get its GABA-transaminase inhibitor vigabatrin (Sabril) on the market: It received confirmation from the Food & Drug Administration of a tentative date for an advisory committee meeting.

Given that FDA has held 30 advisory committee meetings so far this year, that doesn’t sound like groundbreaking news. But in the case of Sabril, it’s a major development given the difficulty FDA has had in finding enough qualified advisory committee members under the new conflict of interest guidelines.

We wrote about Sabril as a worst-case example of the approval delays in the new user fee era in last month's issue of The RPM Report. But is also a poster child for what can go wrong under FDA's new conflict of interest guidelines. (We'll have more on that on this blog and in the next issue of The RPM Report.)

But for now, here's the short story: An advisory committee meeting for Sabril was originally scheduled for August, but there was one (tiny) hiccup. It turns out that the only pediatric neurologist on the committee, Dartmouth Medical Centers Greg Holmes, did work on the original NDA when it was owned by Sanofi-Aventis predecessor company Marion Merrell Dow.

That’s a definite no-no under FDA’s new guidelines. Holmes was recused, and it has taken until now for the agency to reschedule the meeting for January 7-8, as reported in this week's issue of "The Pink Sheet." Of course, that’s assuming FDA can find a qualified pediatric neurologist who hasn’t run a clinical trial for vigabatrin (or a competitor), or invested more than $50,000 in Ovation (or a competitor), or is conflicted in some other way.

But perhaps the Greg Holmes snafu is only fitting for a drug like vigabatrin, which has already had an excruciatingly long pathway toward approval.

Vigabatrin was developed in the 1980s by Merrell Dow as an anticonvulsant. Three advisory committee were convened (in 1984, 1985 and 1989) in light of toxicity signals seen in animal models. An NDA finally was submitted in 1994 by Marion Merrell Dow; FDA turned it down twice before it was outlicensed to Ovation in 2004 by Aventis (now Sanofi-Aventis).

Ovation has had much more success with vigabatrin, having moved from the licensing deal to a priority review for a more targeted indication of infantile seizures in three years. (Ovation also is pursuing the original indication for use in complex partial seizures; the company submitted a response to FDA's questions about that application late last year.)

FDA's deadline for a decision on both indications was June 27--more than three months ago. Between the missed user fee deadline and the immense difficulty in finding enough experts to staff an advisory committee, Sabril is the worst-case example of drug regulation today.

Will there be more? Probably. Will it be yours? Stay tuned.

Watson’s Rapaflo Sails Through FDA: The Exception That Proves The Rule?

Analysts don’t expect much from Watson’s Rapaflo, a new entrant in the already crowded alpha-blocker benign prostatic hyperplasia category.

But if the drug is any where as good as relieving obstructed bladders as it was at breaking through the bottleneck at FDA, don’t bet against it.

Let’s recap what we know about today’s FDA. The agency doesn’t have the resources to review applications on time. (See “Talent Squeeze at FDA,” The RPM Report, December 2007.) It also has the strategic good sense to realize that now is not the time to make on-time approvals the top priority. (See “The New User Fee Rules,” The RPM Report, March 2008.)

There’s more. “Standard” review applications will receive at least one “complete response” letter before approval—if they are approved at all. (See “The Data Everyone’s Talking About,” The RPM Report, November 2007.) Inexperienced NDA filers shouldn’t kid themselves into believing they will even get a review by FDA. (See “Rejected Out of Hand,” The RPM Report, February 2008.) And products for crowded primary care indications can only come to market in the US if they have been sold forever overseas (See “When Approvable is Good News,” The RPM Report, December 2007) or if they have clear evidence of comparative advantages over existing therapy. (See “Straight Talk From FDA,” The RPM Report, November 2007.)

So, if you had asked us about Watson’s chances on Rapaflo, filed in December under a licensing agreement with Kissei, we’d have bet all our US Treasury bonds that they’d have at least another year to wait before getting the all clear from FDA.

Good thing you didn’t ask. As “The Pink Sheet” reports, Rapaflo received approval from FDA on Oct. 9—three days before the 10-month standard review deadline.

So here’s a drug entering a huge primary care market (we found one estimate that there are 115 million men worldwide with BPH) approved based on clinical trials in less than 1,000 patients. It has only minimal global market experience (two years in Japan). The sponsor—Watson—is still far better known for its generic drug applications than its new drug savvy, and there are already four brands available in the same class for the same indication.

Can this be the same FDA that just imposed a formal risk evaluation and mitigation strategy on a drug that isn’t even marketed anymore? (It is—FDA is requiring a REMS for Exubera.)

Maybe FDA read the analyst reports, which suggest Watson will have at best modest success (say $50 million a year) selling Rapaflo in a generic-first class. But we doubt it. This is definitely a clear sign that the old model FDA is completely dead yet. Product by product, division by division, there are still openings for these kind of approvals.

Though we still wouldn’t build our business on expecting too many more Rapaflo’s in the years to come…

What's the Secret of Comedy ... and PR?*

Our colleagues at the Tan Sheet think the Consumer Healthcare Products Association, the trade group representing over-the-counter drug manufacturers, has a handle on the latter, given the timing of their announcement today that their members plan to relabel OTC pediatric cough cold products “do not use” in children under 4.

The announcement garnered industry headlines like this: Drug companies: No cold medicines for kids under 4. The relabeled products including some in Novartis’ Triaminic Line, McNeil’s Tylenol line and and some from Procter & Gamble, Reckitt Benckiser and Wyeth Consumer Healthcare (a full list is here) will be on shelves within weeks, under a plan the association worked out with FDA's blessing - well before the agency's Part 15 hearing held last Thursday to gather information on the products.

Notably, both the agency and the association kept mum at the hearing about the relabeling plan.

As a result, petitioners seeking to have pediatric cough/cold products off the market for children under 6 didn’t get a chance to pick at the plan at the widely covered event, and industry is able to announce a public safety initiative that appears to address at least part of the program in the next news cycle.

Which had some reporters griping at FDA today when the agency held a press call on CHPA’s plan. “Why couldn’t you have brought this little tidbit up during the nine-hour meeting on exactly this topic last week?” was the gist of the complaint. FDA’s director of the Office of New Drugs, John Jenkins, and drug center head Janet Woodcock said they deferred to CHPA on the announcement and split a hair, saying the meeting was about proposed changes to the OTC monograph, not about short term industry efforts. Given FDA’s recent track record on public relations, this isn’t too surprising.

For an in depth look at FDA’s meeting and some clues to agency thinking about revising the OTC monograph for the products, see “The Tan Sheet” here.

--Chris Walker

*(timing.)

Obesity Drugs: Another One Bites the Dust

From time to time here at the IN VIVO Blog, we write about something not because it’s a clever deal, or a shocking policy out of Washington, or an interesting industry trend that we think you should be aware of—but simply because we were right.

This is one of those times.

Merck has decided to discontinue development of taranabant, its cannabinoid-1 receptor blocker in Phase III development for obesity. Why? Well, in short, the only doses that were effective in weight management also had an unacceptable level of psychiatric adverse events.

Indeed, Merck had already dropped the two high doses of taranabant in clinical studies (4 mg and 6 mg) due to statistically significant differences in crying, mood swings, anxiety and depression. At the lowest dose (2 mg), patients reported the same adverse events, although the results were not statistically significant.

The problem was that the efficacy at that low dose wasn’t terribly impressive. Among those patients, 57% lost 5% of their body weight and 28% lost 10% of their body weight. That sounds nice, but when you consider that these are obese patients with a body mass index of at least 30 kg/m2, it’s really not that much to lose—especially in light of the psychiatric adverse event trend.

Given that taranabant is in the same class of drugs as Sanofi-Aventis’ rimonabant (once Acomplia, later Zimulti), and had pretty much the same profile, we saw this one coming. We probably weren’t alone in that thinking, but we’ll continue with the shameless self-promotion anyway—click here for that story in The RPM Report.

But we also have to applaud Merck for having the courage to put a dead drug down—instead of being so blinded by dollar signs as to fail to see that there’s no chance for FDA approval until deep into the drug review process. Of course, when you bank much of a future franchise on a single product, it can be hard to see the forest through the trees.

The taranabant failure happened despite—or perhaps because?—Merck hired two prominent FDA officials that could offer advice on the application: Robert Meyer, the FDA division director that was in charge of reviewing taranabant, and Peter Honig, who was a prominent drug safety official in his days at the agency.

Perhaps it was that expertise that helped convince Merck of the bigger picture. FDA isn't going to approve a relatively ineffective drug that has that kind of a safety signal—especially given the agency's recent crackdown on drugs with psychiatric adverse events.

Or maybe Merck knew that already. Regardless, one thing is clear: like so many others before it, cannabinoid-1 receptor blockers are proving to be a tough drug class. Taranabant is just the latest drug to fall.

FDA Hires a PR Firm to Tarnish its Image

It’s only appropriate that on the day of the Vice Presidential debate, Alaska Newspapers Inc. is making front page news.

But it’s not for the reason you may think.

The Washington Post has a top story today on how FDA circumvented the government competitive contracting rules in order to ensure that Qorvis Communications received a $300,000 public relations deal.

Alaska Newspapers served as the middleman. How’s that, you ask?

The group doesn’t have to compete for federal contracts because it qualifies for special set-asides. So, ANI would get the deal and hand it off to Qorvis. And that’s exactly what they did, according to the WashPost.

FDA deputy commissioner for operations John Dyer, a former CMS official, said in the story that the contract has been suspended and that the agency has launched an internal investigation.

FDA Commissioner Andrew von Eschenbach and other senior officials did not know about the no-bid contract, Dyer says in the story.

Von Eschenbach has been besieged with criticism of the agency from various sides for two years. He must be feeling the wear and tear but this is the kind of project that should have been brought to his attention.

It would be a good idea for the commissioner to know the FDA had hired the same PR firm that works for PhRMA “to create and foster a lasting positive public image of the agency for the American public,” as the Washington Post describes.

As I recall, FDA’s perceived “cozy” relationship with the drug industry has been an issue of public concern lately.

The fact that the FBI raided Qorvis for work the company did on behalf of the Kingdom of Saudi Arabia back in 2004 probably should have raised a red flag as well when it came to choosing the right firm. Is there a PR company shortage I was unaware of?

Former FDA associate commissioner for external affairs Peter Pitts has some interesting behind-the-scenes insight on outsourcing PR. To read it, click here.

This most recent development has four major impacts on FDA:

1) Further supports the public perception that FDA is dysfunctional.

2) Undermines the leadership of von Eschenbach. Where was he on this thing?

3) Needlessly stigmatizes FDA by lumping the agency with other politicized no-bid contracts. Is FDA synonymous with Halliburton?

4) Triggers yet another Congressional probe by the House Energy & Commerce Committee.

Chairman John Dingell (D-Mich.) says his committee will investigate the matter, which could result in a high-profile hearing. Here’s what happened last time von Eschenbach went up to Capitol Hill.

It's a sign of FDA's fortunes when the agency goes out of its way--and budget--to hire a PR firm to improve its public image, tarnishes its image in the process, gets a Congressional investigation out of it, and still doesn't have a PR agency.