Wednesday, September 10, 2008

Celgene and FDA’s New Drug Safety List

It’s over for Celgene. That’s it. Revlimid’s done. Investors should evacuate the premises immediately.

After all, a vital cog in Celgene’s cancer portfolio is on FDA’s first quarterly drug safety posting.

Sound too alarmist? Maybe a little extreme? Of course it is. But that’s how a good number of investors reacted to the posting.

Celgene lost about 3% of its value in the two days following the announcement. Not terrible. But if you look at trading the day of the announcement, volume more than tripled and the stock dropped 6% of its value in midday trading with a low of $63.00 per share before edging back up.

We’ve seen that investors and drug companies are finding it challenging to communicate and interpret risk, respectively. To read our take, click here.

FDA threw a new twist into the risk communication equation last week. In response to a specific provision in the FDA Amendments Act, the agency will be posting a list of drugs every three months that officials deem worthy of further risk evaluation following voluntary adverse event reports from patients and health providers. So for all of the FDA critics out there, this is something the agency had to do.

In a September 5 press release announcing the initiative, FDA tried to be as unalarmist as possible. “My message to patients is this: Don’t stop taking your medicine. If your doctor has prescribed a drug that appears on this list, you should continue taking it unless your doctor advises you differently,” said Janet Woodcock, M.D., director of FDA’s Center for Drug Evaluation and Research.

The agency was very explicit about what a drug showing up on the list actually means for that drug:

“The appearance of a drug on this list does not mean that FDA has concluded that the drug has the listed risk, or that FDA has identified a causal relationship between the drug and the listed risk. It is on the list only because FDA has identified a potential safety issue.”
In a media briefing prior to the official announcement, Office of Surveillance and Epidemiology director Gerald Dal Pan explained that a listing on quarterly report means FDA has begun an analysis of whether the drug needs further evaluation such as further information, clinical trials, epidemiologic study, need to conduct an epidemiologic study, and possibly the need to conduct a clinical study.

CDER associate director for Safety Policy and Communication Paul Seligman said two things have to happen to get on the quarterly list: first, a provider submits an AER report to FDA’s voluntary AERS reporting system. Second, our FDA staff have judged that further follow up or review is warranted.

Seligman highlighted that the work FDA is doing to support the quarterly list isn’t anything new. “This is work we’ve been doing for decades.” What’s new is, he says, FDA is telling the public what it’s working on in postmarket surveillance at the “earliest stage.”

FDA’s new initiative is not without some irony. The first quarterly report, which is supposed to represent FDA’s work at the “earliest stage” is for January 2008-March 2008, not the just passed April 2008-June 2008 quarter. That is understandable since FDA has a seemingly limitless number of FDAAA provisions to implement and a very limited number of resources to get it done. We’re just pointing it out. There were similar issues with FDA’s “early communication” initiative, which appeared to be anything but early. To read more, click here (also one of our favorite blogs and blog pictures.)

Here’s the first list of 20 drugs on the quarterly post:

Potential Signals of Serious Risks/New Safety Information Identified by the Adverse Event Reporting System (AERS) January - March 2008

Product Name: Active Ingredient (Trade)
or Product Class

Potential Signal of Serious Risk/New Safety Information

Arginine Hydrochloride Injection (R-Gene 10)

Pediatric overdose due to labeling / packaging confusion

Desflurane (Suprane)

Cardiac arrest

Duloxetine (Cymbalta)

Urinary retention

Etravirine (Intelence)


Fluorouracil Cream (Carac) and Ketoconazole Cream (Kuric)

Adverse events due to name confusion


Anaphylactic-type reactions

Icodextrin (Extraneal)


Insulin U-500 (Humulin R)

Dosing confusion

Ivermectin (Stromectol) and Warfarin

Drug interaction

Lapatinib (Tykerb)


Lenalidomide (Revlimid)

Stevens Johnson Syndrome

Natalizumab (Tysabri)

Skin melanomas

Nitroglycerin (Nitrostat)

Overdose due to labeling confusion

Octreotide Acetate Depot (Sandostatin LAR)


Oxycodone Hydrochloride Controlled-Release (Oxycontin)

Drug misuse, abuse and overdose

Perflutren Lipid Microsphere (Definity)

Cardiopulmonary reactions

Phenytoin Injection (Dilantin)

Purple Glove Syndrome

Quetiapine (Seroquel)

Overdose due to sample pack labeling confusion

Telbivudine (Tyzeka)

Peripheral neuropathy

Tumor Necrosis Factor (TNF) Blockers

Cancers in children and young adults

That’s it. That’s all you get. No numbers of reports and no nature of the seriousness of the adverse events reported.

So back to Revlimid. The drug was associated with reports of the serious skin rash Stevens Johnson Syndrome. As you may recall, SJS was the reason the COX-2 inhibitor Bextra was taken off the market.

We’re not doctors (we don't even play them on TV), but two observations which should quell any investor jitters based on the very little we know so far.

First, if you’re taking Revlimid, a drug used for MDS and multiple myeloma, the potential for SJS is likely the least of your concerns. Second, Revlimid carries one of the most comprehensive, thorough risk management plans (RevAssist) of any drug on the market managed by a company that revolutionized the efficacy of risk management plans for thalidomide, arguably the most dangerous drug ever marketed. If there are more cases, FDA can rest assured RevAssist will catch them.

So what do you think? Is this quarterly list a good idea or a bad one? Are we getting in too deep and too early when it comes to FDA’s postmarket responsibilities? Per usual, we’d love to hear your take.

1 comment:

insider said...

The FDA's just catching up.