While You Were Eating Beignets...

It's the first weekend in December and that means it's time once again for the American Society of Hematology meeting. This year, reps from biotech and pharma travel to N'awlins to make news--or at least issue press releases--before the last year of the first decade of the 21st century comes to a close.

And for the foodies/cultural mavens in the industry, how can you blame them? Where else can you indulge in chicory coffee, beignets (essentially fried dough, but the French makes it sounds waaaay better), and gumbo, while also soaking up the music scene?

If you weren't at ASH, you were likely debating the merits of football's popularity contest, aka the Bowl Championship Series, or Tim Tebow's oscar-winning performance after the Gators lost to Alabama. Or maybe you were engaged in that annual ritual now closely tied with propping up the national economy...filling recycled, reusable bags with unnecessary plastic items manufactured in China.

Away from food, footballs and rituals: this week's dealmaking got off to a healthy start, with Celgene announcing it was buying private firm Gloucester Pharmaceuticals for $340 million in cash, plus up to $300 million in future US and international regulatory milestones. The deal further strengthens Celgene's cancer franchise--more specifically, its blood cancer franchise--as Gloucester's romidepsin (Istodax), a histone deacetylase inhibitor, was approved by FDA in November for cutaneous T-cell lymphoma.

Not that Celgene's early Monday morning shopping should overshadow our hand-picked selection of the weekend events that happened while you were searching in vain for a $10 Zhu Zhu hamster... (Fuhgedabout it!)

New Yorker's Atul Gawande analyzes the current health care reform bill under review in the Senate. The fact that there is no grand master plan for curbing costs is actually a good thing, he argues. (If you haven't read Gawande's latest, you should. He's required reading in the West Wing.)

The WSJ reports Obama went to the Hill to urge the Dems to stay united as the Senate debated a proposed compromise option to the public plan. Meanwhile NYT's Prescriptions Health Blog outlines the advantages of a hybrid plan, the Federal Employees Health benefits Program.

There's lots for Sharfstein and Hamburg, the FDA's dynamic duo, to keep an eye on as they promote their safety first agenda. This weekend news surfaced that a Fresno, CA-based company recalled 22,723 ounds of ground beef potentially linked to salmonellosis; and then there was the NYT article on the safety of plasma products.

Also in the NYT this weekend, a story on the outsized pricing of cancer med Folotyn. The article is sure to spark renewed debate from payers about reimbursement for high priced meds that add just a few months of life. That's bad news for pharmas looking to cash-in on this specialty market.

ASH-related headlines: Cell Therapeutic's pixantrone increases median survival by 3.3 months in patients with relapsed/refractory NHL; Onyx/Proteolix presented updated Phase IIb data from studies of their next-generation proteosome inhibitor, carflizomib; privately-held Gloucester Pharmaceuticals presents additional data on newly approved ISTODAX in cutaneous T-cell lymphoma.

It wasn't just cancer at ASH; new data about next-generation blood thinners from Johnson & Johnson and Boehringer Ingelheim were reported at the meeting in conjunction with an article in the NEJM.

(Image by flickrer and[w] used with permission through a creative commons license.)

Surprise! Drug Approvals Increase In 2008

Missed user fee deadlines. Multiple cycle reviews. A regulatory posture defined by the phrase “Safety First.” Complex new legislation. Understaffed, overworked review divisions. A hostile Congress eager to second-guess any and every decision. Divergent viewpoints built into the review process. Demands for more advisory committees with fewer conflicts of interest.

No wonder it is harder than ever to get drugs through FDA.

Maybe not.

The approval of Eisai’s antiseizure medicine Banzel (rufinamide) on November 14 marked a quiet milestone for FDA’s Center for Drug Evaluation & Research, the group charged with reviewing all new drugs and most therapeutic biologics: it is the 18th new molecule approved by the agency this year.

That matches the full year tally for 2007, and there are still six weeks left in the year. [UPDATE: With two approvals in the 24 hours since this was first posted, FDA is now at 20 new molecules for the year.]

Don’t run out and buy all the champagne quite yet: remember, 2007 was the single worst year for new drug approvals in a quarter century. Matching that performance is hardly cause for a parade.

But it is good news nevertheless. As recently as July, it looked like FDA might be on track for yet another new low in output: with only six approvals in the first half of the year—one fewer than the first half of 2007.

Well, the pace has picked up (as we predicted it would). And with at least 10 more applications still pending with a shot at approvals this year, it may turn out that 2008 is the best single year for approvals since 2004. (CDER approved 36 novel products that year. Don't expect miracles: five or six more approvals maybe, but 18 more approvals in the next six weeks is out of the question.)

Even a really strong finish by FDA in 2008 wouldn’t mean that much in the grand scheme of things. After all, 2004 was just a one-year blip in what has been a prolonged drought in new product approvals—at least compared to the 1990s. What industry needs is not one big year, but a long term, sustained increase in the output of new products coming to market.

Still, the thought that FDA will end up approving more drugs this year than last offers a much needed sign of hope for the biopharma industry. Maybe—just maybe—the new era in drug regulation ushered in by the FDA Amendments Act of 2007 won’t be so bad after all.

Industry accepted FDAAA as a tough but necessary trade, hoping that the tighter safety regulation would give FDA more confidence to approve drugs that would otherwise languish at the agency. There’s no question about the tougher regulation: as “The Pink Sheet” reported, about one-third of new molecule approvals have a formal Risk Evaluation & Mitigation Strategy attached to them, and more than half have mandatory post-marketing study requirements.

Its impossible to say for sure whether the other half of the trade will come to pass, but at least the trend is in the right direction.

In fact, Banzel may be the perfect emblem for the year 2008. It was a multi-cycle review (the application was first submitted almost exactly three years ago); it slipped passed the final review deadline (Eisai’s resubmission was due for action on Aug. 29); and the approval carries with it a formal REMS requirement as well as some mandatory post-marketing trials.

But it is approved for marketing. And, despite everything, that is something that seems to be happening a bit more often this year than last....

Balancing Drug Safety and Drug Approvals

Well, it’s official.

FDA’s drug review and drug safety offices have set aside their differences and hammered out an agreement that more equally divides regulatory authorities on issues related to drug safety.

This is a significant change in drug safety policy at FDA: the Office of Surveillance & Epidemiology—seen by some drug sponsors as not quite as friendly to industry as the Office of New Drugs—will now have a greater voice on regulatory issues related to drug safety. In the past, OSE had served in more of a consulting role to OND.

This brave new world was pushed by Center for Drug Evaluation & Research director Janet Woodcock as part of the “Safety First” initiative in response to some very public disagreements between FDA officials on drug safety issues. (You can read more about that in an interview with Woodcock that appeared in The RPM Report.)

While we wrote about the plan to redraw the lines of authority in a previous post, we just got our hands on the memorandum of agreement that makes the deal final. The MoA—between Office of New Drugs director John Jenkins and Office of Surveillance & Epidemiology director Gerald Dal Pan—took effect June 30 and was announced to FDA employees by Woodcock on July 1.

Under the agreement, the drug review and drug safety offices will share equal responsibility on “significant safety issues” for pending and approved products.

Examples include:

1) Safety labeling changes;
2) Submitting and implementing a REMS;
3) Requiring a post-marketing study or clinical trial;
4) Discontinuing marketing of a product;
5) Implementing an educational plan; and
6) Modifying promotion or advertising

Any disputes would be referred to Woodcock; both Dal Pan and Jenkins expect most issues will be resolved without involving the CDER director. Speaking during a town hall meeting at the Drug Information Association annual conference last week, Dal Pan said it will be a “very rare occurrence” to go to Woodcock—or even the office directors themselves—to resolve a difference of opinion. Most disputes will be handled by the office staff, he said.

Under an even bigger change, OSE will be designated as the lead office for certain regulatory actions regarding drug safety:

1) Observational epidemiological studies; and
2) Medication error prevention, including the proprietary name review process

Perhaps even more importantly, OSE will eventually add additional authorities as it staffs up its office and builds its organizational capacity, including pharmacovigilance activities, risk management plans, and the review of carton and container labeling and packaging.

While authority over regulatory actions associated with approvals will continue to reside at OND, responsibility for certain approvals of supplemental applications will eventually be transferred to OSE, the agreement says.

Woodcock said she sees the agreement as “just the first major step” toward creating a new culture at CDER—one that “supports the work of multidisciplinary teams, provides an environment where each member of the team has an opportunity to express his or her view, and ensures an avenue for promptly raising unresolved differences of opinion through the management chain for prompt resolution.”

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

Janet Woodcock’s To Do List For CDER

Given that Janet Woodcock has been back at the Center for Drug Evaluation & Research for six months now (with two months as permanent director), we figured it was high time to check in and see what she’s been up to.

The answer? Quite a bit.

As Woodcock told The RPM Report in an interview, she's the kind of person that likes to get things done. So upon returning to CDER last October, Woodcock settled on two immediate objectives:

(1) Gaining direct hire procedures from HHS’ Office of Personnel Management.

(2) Dedicating more attention on post-marketing safety.

Check and check.

As a result of Woodcock’s efforts, FDA just won direct-hiring procedures from HHS and has since embarked on a major hiring initiative to staff up its scientific ranks. CDER alone will hire 663 employees—444 new positions and 219 in backfill. The hiring frenzy will eventually help end the “lean years” at FDA, when the agency's regulatory mandate outstripped its available resources.

On post-marketing safety, Woodcock launched the “Safety First” initiative last October, putting post-marketing drug safety on par with new drug approvals. As part of that multidisciplinary, team-based approach, the Office of Surveillance & Epidemiology is now an “equal partner” with the Office of New Drugs. Remember those public fights over Avandia and Ketek? Woodcock hopes that "Safety First" will put those to rest.

Of course, there are still challenges ahead. CDER needs to train all those new hires, and the Center is still feeling its way on the “Safety First” initiative and implementation of the FDA Amendments Act in general.

And then there’s the issue of those new risk evaluation and mitigation strategies, or REMS, which have Woodcock weighing in on new drug applications more than usual. For more on that, as well as the status of drug approvals under her stewardship, click here. If you're not already a subscriber to The RPM Report, you can sign up for a free trial to view the article.