GDUFA? Probably Not This Time

We had an interesting discussion today on the state of the FDA and the impact of the power shift in Washington. Joining me on the conference call, which you can access by clicking here, were biotech PDUFA negotiator Amit Sachdev and former Senate Health Counsel Steve Irizarry.

We touched on way too many issues to discuss here, but one intersting thing to come up was generic drug user fees. The idea of user fees for generic drugs was pushed by senior FDA officials earlier this year. In fact, a senior policy person at the generic drug industry's trade organization - GPhA - just left to join FDA's policy shop to work specifically on generic policy.

But from the sounds of it, generic drug user fees aren't happening for now. It sounds like it could take a while to hammer out. One scenario could have an abbreviated biologics pathway attached to GDUFA legislation at some point down the road, if it doesn't happen in stand-alone legislation proposed by Henry Waxman and co-sponsored by Senator Hillary Clinton.

BIO's Sachdev said that the new Congress gives BIO an "opportunity" to "educate" new members on biologics and the complexities behind the follow-on biologic debate. I think everyone can read between the lines.

A Clean Sweep: The End of an Era At FDA?

Wow. Everyone was expecting the Democrats to take the House, but the Senate too? That was a real long shot considering the entrenched incumbents up for reelection. Washington is reeling from the total shift in the balance of power and the overnight change in leadership.

So where does that leave FDA?

For the FDA, 2006 may be remembered as the end of the pro-innovation and pro-industry era at the agency. Since Mark McClellan was put in place, FDA has been as friendly as ever with drug companies and biotechs. Friendly, not cozy. In other words, McClellan, Crawford and now von Eschenbach have created an atmosphere of openness, transparency and communication. Senior officials have made it a point of speaking openly with Wall Street and the media about policy, to provide some predictability. You can argue whether that's good or bad.

But the FDA will be monitored more closely than ever. Some analysts and pundits are saying the Dems will tread lightly despite all of their accusations of corruption and coziness. That will be true in some areas. But FDA and drug companies do not fall in those areas. There is bi-partisan agreement that drug safety reforms are a priority. It's the so-called "low hanging fruit" that House and Senate Dems in leadership positions will go after.

The individual drug reviewer now has a "very friendly" Congress at their disposal if they think a regulatory decision on a particular drug or policy is being forced down their throats. You can count on that. Before November 7, they had Charles Grassley and Ted Kennedy. Now they have the entire House and Senate.

Drug Safety Reforms in 2007: Part I

We're just a few days away from Black Tuesday regardless of which Party you're throwing your support behind. While there's a lot at stake for the average citizen, the stakes are tripled for the pharmaceutical and biotech industries.

It now looks all but certain that House leadership will change hands over to Democrats. The Senate looks like a toss-up. If this scenario plays out, there is sure to be drug safety reforms to take place.

Over the course of the next weeks, we'll take a look at some of the changes we think will and won't take place. But let's start with those that won't. The one thing FDA has been dreading is any proposal that calls for splitting up its drug center (CDER) into two premarket and postmarket centers. In its current structure, CDER reviews drugs and approves them as well as monitors them for risks or safety issues once on the market. Some drug safety experts and lawmakers have called for such a reform. Senator Chuck Grassley, who chairs the Senate Finance Committee and is FDA's most vocal Republican critic, made it the centerpiece of his reform legislation co-sponsored by Dem Chris Dodd of Connecticut.

There were rumors that the Institute of Medicine committee on drug safety was thinking about recommending such a measure in their long-awaited report. CDER head Steve Galson called splitting the center up "dangerous." A number of top officials reached out to committee members behind the scenes to lobby against the recommendation.

It worked. The IoM committee left that recommendation out. FDA is breathing a sigh of relief. Not only would it have hurt drug safety efforts (since the drug reviewers are the ones that know the most about a particular drug's risks) it would have severely weakened the position of the CDER director.

The IoM report is serving as the catalyst for any changes that take place as a part of the drug safety debate on Capitol Hill. In other words, in order for it to happen on the Hill, it probably has to be in the IoM report.

In FDA's view, the agency dodged a bullet.

Next: We'll look at the drug safety impact on the individual reviewer.

FDA and CMS Come Together Again

Greetings to all. It's been a long time since our last post, but The RPM Report is trying to double its efforts in posting some useful insight into FDA, CMS and health policy. So that means a post every six months...kidding.

I wanted to bring your attention to two events coming up powered by The RPM Report. The first is an audioconference on November 14 titled: "The State of FDA: Drug Reviews, Policy and the IoM Report." The conference call will feature former FDA policy czar Amit Sachdev, former Hill health advisor Steve Irizarry and yours truly. You can find out more at by clicking on this link.

The second event is the biggest health policy and regulation meeting on the drug industry in Washington, D.C.: The RPM Report's FDA/CMS Summit for Biopharma Executives. If you operate in th edrug industry and you are a decision maker, then you should attend, period. Last year featured CMS Administrator Mark McClellan, FDA Commissioner Andrew von Eschenbach and all of the key government figures that are critical to the way drug and biotech companies do business. This year features the same lineup. You even get a free iPod Nano if you register early enough (hurry up though).

Check both of these events out so you'll know more next time you go into a company meeting.

Omnitrope Victory Narrows FDA's Options On Biogenerics

By Ramsey Baghdadi

A federal court decision in favor of Novartis AG's Sandoz unit for its follow-on human growth hormone somatropin (Omnitrope) gives the US Food and Drug Administration one less delay tactic in the debate over an abbreviated pathway for biogenerics.

The US District Court for Washington, D.C. granted Sandoz summary judgement on the Omnitrope application, which was filed in July 2003, essentially mandating that FDA make a regulatory decision on the application.

The decision is a clear-cut loss for FDA, according to Steven Irizarry, VP-government affairs with ML Strategies. "The tone of the memorandum is very important," Irizarry said of District Court Judge Ricardo Urbina's decision memorandum. "The court is going to be very wary and look with a scrupulous eye at what FDA does."

But the issue is far from resolved. In fact, the court decision alone is not enough to force FDA to make a "yes or no" answer on a regulatory route for follow-on biologics in general--or even for Sandoz' application in particular. FDA will most certainly appeal the ruling. The agency could also take a regulatory action without making a final decision by issuing a "non-approvable" letter or an "approvable" letter, which is less harsh, but can turn out to be practically equivalent. For example, Bristol-Myers Squibb's diabetes drug muraglitazar (Pargluva) was deemed "approvable" but Bristol and its marketing partner Merck chose to scrap the program altogether rather than going down the road of collecting more clinical data.

Still, the court victory is exactly what proponents of follow-on biologics wanted. The ruling puts the ball squarely in FDA's court and forces them to make a move that will undoubtedly be harshly dissected in the public domain, no matter which direction the agency chooses to go in.

FDA has revealed its cards regarding the course the agency will take on the regulatory front. In a March 17 letter, FDA associate commissioner for legislation Patrick Ronan said the agency would not issue product-specific guidance and, instead, would create guidance "more broadly applicable" to follow-on protein products (FOPPs). Ronan's letter was in response to a February 10 letter co-authored by Utah Republican Senator Orrin Hatch and Democratic California Congressman Henry Waxman asking for biogenerics guidance on insulin products and human growth hormone, specifically.

Of course, a more general guidance-or "white paper"-will take considerably longer than documents focused more specifically on product categories. Companies interested in pursuing FOPPs will have to continue using a strategy of "incrementalism" while FDA delays an abbreviated pathway indefinitely(See "Biogenerics Are Happening," The RPM Report, January 2006).

The most likely outcome is an appeal by FDA and the subsequent release of a legal backgrounder on all biologics approvals up to the present. That kind of move would delay another decision on the legal front and somewhat appease the growing calls for action by the agency. One interesting option at FDA's disposal is to issue a notice asking for a hearing with Sandoz. Within 30 days, Sandoz would choose to either accept or reject the request. If they accept, that would start another 180 day clock, which would delay a decision by at least another 210 days. Sandoz would almost certainly deny any request for a hearing. The Novartis unit's next step will likely be to file a motion for a decision on the Omnitrope application within a specified short period of time.

But don't expect a white paper on follow-on biogenerics anytime soon. FDA remains in the driver's seat until Congress decides to step up it's interest on the matter. And piquing the interest of key lawmakers on Capitol Hill in an election year will be a tough sell.

Comments? E-mail the author at rbaghdadi@windhover.com

Enemies or Frienemies in the Religious Right?

I keep reading in the lay media about efforts by Christian lobbying groups to undermine the development of a vaccine against human papilloma virus -- the sexually transmitted infection that causes cervical cancer. If those stories are to be believed, there are massive campaigns afoot to prevent Merck and GlaxoSmithKline from ever recieving FDA approval of their late-stage HPV vaccines, Gardasil and Cervarix.

But that doomsday scenerio doesn't appear to be playing out.

I have never been a friend of the religious right, and those early murmurings of a plan to block an HPV vaccine made my blood boil. But most respectable Christian lobbying groups have either reluctantly agreed that the public health benefits of an HPV vaccine far outweigh the potential for increased sexual promiscuity, or they have decided to stay quiet on the issue. One prominant group, the Christian Coalition of America, actually supports HPV vaccine development.

While this may be wishful thinking, it seems that the (ill-founded) social-political arguments against HPV vaccination won't stand in the way of FDA approval.

Not that GSK hasn't tried: the company floated the idea to analysts of positioning its "cervical cancer vaccine" Cervarix against Merck's "STD vaccine" Gardasil. Not only did investors not bite, some were downright offended that GSK would take that tact.

For now, at least, it seems that GSK has put that argument on the back burner, freeing Merck up to address perhaps an even greater challenge: figuring out the details of what will need to be an enormous patient and physician educational effort.

FDA Becoming Conservative? Not So Fast

I have attended a number of meetings and panels of late and keep hearing the same thing over and over: FDA is more conservative. It seems that every speech starts: "With a more conservative FDA..."

I'm not so sure.

There are some developments that could lead one to say FDA is becoming more conservative, such as the recent creation of an Office of Drug Safety and the choice of a new director for that office.

http://www.fda.gov/bbs/topics/news/2005/new01245.html

But if you look more closely, the office will fall under the purview of the Center for Drug Evaluation & Research and the new director ultimately reports to CDER chief Steve Galson. Moreover, the new ODS Director - Gerald Dal Pan - is only a few years removed from the industry he helps to regulate now. Dal Pan formerly oversaw clinical research for Guilford Pharmaceuticals. He left that post in 2000 to join the agency.

And take a look at the new interim FDA Commissioner. Andrew von Eschenbach is most known for saying that his goal as the head of NCI is to have a cure for cancer by 2015.

So he has a meager 10 years left to accomplish that feat.

[If what FDA says and does matters to you, then make sure to attend the upcoming FDA/CMS Summit Nov. 29-Dec. 1 in Washington, D.C. A number of FDA topsiders and former FDA decision makers will be there to tell you their priorities in 2006 and help you find your way through the regulatory maze.]

Review times certainly haven't skyrocketed and the agency is looking for more ways to speed up reviews, such as rolling review under its Pilot 1 program, which could be made permanent under PDUFA IV.

Merck's Vioxx clearly has created the environment for people to say FDA is becoming more conservative, but that doesn't mean that they are. The agency's Endocrinologic & Metabolic Drugs Advisory Committee just voted in favor of approving Pfizer's inhaled insulin drug Exubera, a product that has a decade-old safety history. The Oncologic Drugs Advisory Committee just recommended accelerated approval for Celgene's Revlimid for a type of blood cancer known as MDS. Revlimid is a cousin of thalidomide, one of the more dangerous drugs out there and that has been used in over 130,000 Americans to date.

Even if you take a look at the COX-2s and NSAIDs, Pfizer's Celebrex remains on the market, although with a black box warning, as do all other prescription NSAIDs.

If you take a step back and look at the key personnel at FDA, the players are still the same: Janet Woodcock, Bob Temple, and Galson among others.

I think the real issue for discussion is Big Pharma's pipeline. It's not that FDA is becoming more conservative, it's the pipeline of drugs leading into the agency.