Genentech, Inc (SOUTH SAN FRANCISCO, California) announced that the company has issued a Dear Healthcare Provider letter to inform potential prescribers in the US of a case of progressive multifocal leukoencephalopathy (PML) in a 70-year old patient who had received its drug, Raptiva^® (efalizumab), for >4 years to treat chronic plaque psoriasis. PML was diagnosed based on detection of John Cunningham (JC) viral DNA in cerebrospinal fluid, clinical symptoms, and MRI findings. The patient had not received other systemic immunosuppressants. The company will work with the US FDA to update the prescribing information for the therapy and to determine if further action is needed. There are no known interventions that can reliably prevent or adequately treat PML.

The case was recently reported by the company in late September as part of its ongoing safety monitoring and surveillance program. Based on the medical information available to date, Raptiva may have had a contributory role in the development of PML in the patient. There are no other cases of confirmed PML in patients treated with the drug, although a 62-year old patient developed progressive neurologic symptoms and died of unknown cause. Information about that case is also included in the issued Dear Healthcare Provider letter.

In accordance with regulatory requirements, Merck Serono Intl (a division of Merck KGaA, Darmstadt, Germany) has informed regulatory agencies in its marketing territories outside the US and Japan about this serious adverse event. Study investigators and ethics committees are being notified of the PML case, and Merck Serono is working with the European Medicines Agency and other regulatory agencies in taking the same cautionary steps as its US counterpart, Genentech.

Patients who are currently on Raptiva therapy or considering taking it should discuss with their physicians the benefits and risks of the drug. As described in the package insert, some patients have had severe worsening or new forms of psoriasis while taking or after stopping Raptiva. It is important for patients not to change or stop treatment without first talking with their physician.

PML is a rare, progressive, demyelinating disease of the CNS that usually leads to death or severe disability. PML is caused by activation of the JC virus, which is latent in up to 80% of healthy adults, typically only causing PML in immunocompromised patients. The factors leading to activation of the latent infection are not fully understood, though abnormalities in T-cells may be important for reactivation and PML. PML has been reported in the published literature in HIV-positive patients, immunosuppressed cancer patients (including patients with hematologic malignancies), organ transplant recipients, and patients with autoimmune diseases.

Raptiva is an immunosuppressive, humanized therapeutic antibody designed to bind to CD11a and in turn impact T-cell activation, adhesion, and migration. In October 2003, the drug received US FDA approval for the treatment of chronic moderate-to-severe plaque psoriasis in adults ≥18 years who are candidates for systemic therapy or phototherapy. Worldwide, ~46,000 patients have been treated; in the US as of July 2008, ~23,500 patients have been exposed to Raptiva for up to 2 years, ~1850 have been exposed between 2 and 3 years, ~700 have been exposed between 3 and 4 years, and at least 400 have been exposed for >4 years.