FDA approves Sylatron for injection for adjuvant treatment of melanoma

FDA has approved peginterferon alfa-2b (Sylatron, Merck) for the adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy.

This is the first such therapy approved for the adjuvant treatment of melanoma by FDA in more than 15 years.

Sylatron’s approval is based on data from the European Organisation for the Research and Treatment of Cancer clinical trial, which was conducted in patients with node-positive melanoma. The trial, "Adjuvant Therapy with Pegylated Interferon Alfa-2b versus Observation in Resected Stage III Melanoma," was published in the July 2008 issue of The Lancet.

The clinical trial was an open-label, multicenter, randomized study that evaluated the safety and efficacy of Sylatron in 1,256 patients with surgically resected, American Joint Committee on Cancer stage 3 melanoma within 84 days of regional lymph node dissection. Patients were randomly assigned to observation (no therapy) (n=629) or to Sylatron (n=627) at a dose of 6 µg/kg by subcutaneous injection once weekly for 8 doses followed by a 3 µg/kg subcutaneous injection once weekly for a period of up to 5 years total treatment. The dose of Sylatron was adjusted to maintain an Eastern Cooperative Oncology Group Performance Status of 0 to 1.

The study’s primary end point was relapse-free survival (RFS), defined as the time from randomization to the earliest date of any relapse or death from any cause. Based on 696 RFS events determined by the Independent Review Committee, the estimated hazard ratio for RFS was 0.82 (95% CI: 0.71, 0.96; unstratified log-rank P=.011) in favor of the patient treated with Sylatron. The median RFS was 34.8 months in patients treated with Sylatron and 25.5 months for patients in the observation group.

Sylatron is contraindicated in patients with a history of anaphylaxis to peginterferon alfa-2b or interferon alfa-2b, in patients with autoimmune hepatitis, and in patients with hepatic decompensation (Child-Pugh score >6 [class B and C]).

The risk of serious depression, with suicidal ideation and completed suicides, and other serious neuropsychiatric disorders are increased with alpha interferons, including Sylatron. Sylatron should be permanently discontinued in patients with persistently severe or worsening signs or symptoms of depression, psychosis, or encephalopathy. These disorders may not resolve after stopping Sylatron.

Sylatron is a once-weekly subcutaneous injection that may be self-injected. The recommended dose is 6 µg/kg/week subcutaneously for 8 doses, followed by 3 µg/kg/week subcutaneously for up to 5 years. Patients should be premedicated with acetaminophen 500 mg to 1,000 mg orally 30 minutes prior to the first dose of Sylatron and as needed for subsequent doses.

"Approval of niche products and higher review intensity by FDA, as seen with Sylatron, are most likely to continue throughout this decade," according to Randy Vogenberg, PhD, principal at the Institute for Integrated Healthcare in Sharon, Mass., and executive director of the Biologic Access & Finance program at The Jefferson School of Population Health in Philadelphia. "This is due to R&D investment targeting by manufacturers as well as concerns over patient safety with biologic therapies in general by FDA. In general both manufacturers and FDA are more risk adverse so the spending is conservative along with new drug approvals.

"For managed care and plan sponsors, this results in new products for highly patient populations that are unlikely to face access restrictions but can result in significant increased expense for medical and/or pharmacy services," added Vogenberg, author of Pharmacy Benefits: Plan Design and Management.