Full article reprinted from "The Pink Sheet" February 24, 2009
Ongoing discussions about a risk management plan for Genentech's Raptiva (efalizumab) may provide an avenue to maintain the psoriasis drug's commercial viability, despite its safety problems. Read on...
Full article reprinted from "The Pink Sheet" February 24, 2009
Ongoing discussions about a risk management plan for Genentech's Raptiva (efalizumab) may provide an avenue to maintain the psoriasis drug's commercial viability, despite its safety problems.
FDA is taking considerably less stringent action than its European counterpart following three confirmed reports and one possible report of the rare brain infection progressive multifocal leukoencephalopathy (PML). On Feb. 19, the European Medicines Agency recommended the suspension of marketing of Raptiva, concluding that its benefits no longer outweigh its risks. The same day, FDA issued a public health advisory about the product.
FDA said that although it has taken a different regulatory pathway than the EMEA, their recommendations to health care providers and patients actually are quite similar: both warn of the need to be aware of the PML risk and the need for close monitoring for neurological symptoms that may represent the rare but fatal brain infection.
Merck Serono, which markets Raptiva in Europe, said in a statement it would work with regulators to comply with the withdrawal request.
FDA Has Experience With PML Risk Management
Part of the reason FDA may feel that Raptiva can stay on the market is the agency's experience with Tysabri (natalizumab), Biogen Idec/Elan's multiple sclerosis and Crohn's disease drug that was pulled from the market due to PML risks but subsequently returned under a risk management plan.
There have been subsequent reports of PML in Tysabri patients, but FDA remains convinced of the utility of the risk management program for a product that is considered an essential treatment.
European regulators traditionally have been more worried about PML issues, and were not as involved in the design of Tysabri's risk management plan.
Tysabri wasn't cleared in Europe until 2007; it was approved in the U.S. for multiple sclerosis in 2005 and then withdrawn in 2006. EMEA also recommended against approval for Crohn's disease in 2007 due to the PML risk; the expanded indication was approved in the U.S. in January 2008.
Will Raptiva's REMS Resemble Tysabri's?
FDA's comfort with PML risk management, however, does not mean Raptiva will have an easy time if it stays on the market. Tysabri's "TOUCH" risk management plan arguably is one of the most restrictive ever implemented (1"The Pink Sheet" DAILY, Dec. 23, 2008).
Genentech and FDA have been discussing implementation of a Risk Evaluation and Mitigation Strategy for Raptiva since the fall. If that REMS were to mirror the TOUCH program - which is also intended to manage the risk of PML - it could mean significant changes to the distribution and administration of Raptiva.
In addition to requiring enrollment by all patients and prescribers, TOUCH requires that only certain pharmacies and infusion sites authorized by the program can dispense and infuse Tysabri, which is administered once every four weeks through IV infusion. Patients are then assessed at each infusion visit (once every month) and every six months by their physician.
By contrast, Raptiva is currently administered once-weekly via subcutaneous injections and can be self-administered at home.
Shifting such a relatively convenient product to only authorized administration sites would be a considerable distribution obstacle for patients. One potential variation to that element of the TOUCH program would be to require limited-duration prescriptions that could only be refilled after a patient had been reevaluated by a physician.
Still, restricted distribution could be better for Genentech than another alternative. While industry has expressed concern about the new oversight powers that FDA was granted as part of the 2007 law creating REMS, the Raptiva case may be a dramatic illustration of what proponents of FDA's new authorities argue: that the new tools actually increase access to drugs by allowing products to stay on the market that otherwise would not.
Genentech also has some experience with another potential benefit of the risk management programs - closer relationships with the doctors and patients who use the companies' products. Genentech works with Novartis on a tightly controlled distribution and product administration program for the injectable allergic asthma treatment Xolair (omalizumab) ("2More Regulation = More Comfort and More Products," The RPM Report, October 2007).
Whether the expense and infrastructure required to support an involved REMS for Raptiva is worth it to Genentech's bottom line remains to be seen.
Analysts at Bernstein predict that the potential withdrawal of Raptiva from both the U.S. and EU markets would have a very limited impact on Genentech, as the drug contributed less than 1 percent ($123 million) of the firm's total 2008 revenue (see sidebar: "3Roche May Have Worst Adverse Reaction To Raptiva Safety News").
For the years 2009 through 2012, they estimate worldwide Raptiva revenue of $114 million, $105 million, $97 million and $90 million, respectively.
In comparison, global Tysabri sales in 2008, shared by partners Biogen Idec and Elan, were $813 million, representing a vital piece of the revenues for both firms.
A Growing Number Of PML Cases
Approved in 2003, Raptiva is indicated for moderate to severe plaque psoriasis (4"The Pink Sheet," Nov. 3, 2003, p. 5).
FDA's advisory for Raptiva follows the growing signal for its association with PML during 2008.
The cases occurred in patients 47 to 73 years of age. All were treated with Raptiva continuously for more than three years, and none were taking other treatments that suppress the immune system. Two of the patients with confirmed PML and the one patient with possible PML died.
Genentech sent out a "Dear Doctor" letter in October after the first case was identified (5"The Pink Sheet" DAILY, Oct. 3, 2008).
Two weeks later, FDA called for a Boxed Warning to be added to Raptiva's labeling to highlight the risks of life-threatening infections, including PML, and directed Genentech to develop a Risk Evaluation and Mitigation Strategy for the drug (6"The Pink Sheet" DAILY, Oct. 17, 2008). The second case of PML was reported the following month (7"The Pink Sheet," Nov. 24, 2008, In Brief).
The rare but fatal brain infection also has struck patients taking Genentech/Biogen Iden's Rituxan (rituximab), for rheumatoid arthritis and non-Hodgkin's lymphoma.
- Jamie Hammon
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