FDA approves Pomalyst to treat AIDS-related Kaposi sarcoma. BMS

Bristol Myers Squibb announced that Pomalyst (pomalidomide) was approved by the FDA for patients with AIDS-related Kaposi sarcoma whose disease has become resistant to highly active antiretroviral therapy (HAART), or in patients with Kaposi sarcoma who are HIV-negative. Patients with AIDS-related Kaposi sarcoma should continue HAART for their HIV as recommended by their physician.

Pomalyst was granted accelerated approval, Breakthrough Therapy designation and Orphan Drug designation in these indications based on overall response rates observed in a Phase 1/II open label, single-arm clinical trial (12-C-0047). Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.

As described in the Boxed Warnings of the prescribing information, Pomalyst can cause fetal harm and is contraindicated in females who are pregnant. Pomalyst is only available through a restricted distribution program, Pomalyst REMS . Deep vein thrombosis, pulmonary embolism, myocardial infarction and stroke can occur in patients treated with Pomalyst and thromboprophylaxis is recommended.

The approval of Pomalyst was based on the findings of a Phase 1/II open-label, single-arm study conducted evaluating the safety, pharmacokinetics and efficacy of Pomalyst in patients with HIV-positive and HIV-negative symptomatic Kaposi sarcoma , the majority of whom had advanced disease. The study was performed under a Cooperative Research and Development Agreement (CRADA) by a team led by Dr. Robert Yarchoan of the HIV and AIDS Malignancy Branch within the Center for Cancer Research of the National Cancer Institute (NCI).

A total of 28 patients (18 HIV-positive, 10 HIV-negative) received 5 mg of Pomalyst, once daily for 21 of 28-day cycles, until disease progression or unacceptable toxicity. All HIV-positive patients continued concomitant highly active antiretroviral therapy (HAART). The trial excluded patients with symptomatic pulmonary or visceral Kaposi sarcoma, history of venous or arterial thromboembolism, or procoagulant disorders. Patients received thromboprophylaxis with aspirin 81 mg once daily throughout therapy. The median time to first response was 1.8 months (0.9 to 7.6). The primary endpoint of the study was overall response rate (ORR), which included complete response (CR), clinical complete response (cCR) and partial response (PR), as assessed by investigators according to the AIDS Clinical Trial Group (ACTG) Oncology Committee response criteria for Kaposi sarcoma. For all patients, the ORR was 71% (95% CI: 51, 87) with 14% (4/28) of patients achieving CR and 57% (16/28) of patients achieving a PR, respectively. The median duration of response for all patients was 12.1 months (95% CI: 7.6, 16.8). Additionally, half (50%) of patients who responded maintained a response at more than 12 months with Pomalyst. The most common adverse reactions including laboratory abnormalities ( greater than 30%) are decreased absolute neutrophil count or white blood cells, elevated creatinine or glucose, rash, constipation, fatigue, decreased hemoglobin, platelets, phosphate, albumin, or calcium, increased ALT, nausea and diarrhea.Adverse reactions were evaluated in 28 patients who received treatment with Pomalyst.

Adverse reactions ( greater than 20%) included maculopapular rash (71%), constipation (71%), fatigue (68%), nausea (36%), diarrhea (32%), cough (29%), dyspnea (29%), peripheral edema (29%), upper respiratory tract infection (29%), muscle spasms (25%), hypothyroidism (21%), dry skin (21%) and chills (21%). Grade 3 or 4 adverse reactions included maculopapular rash (3.6%), diarrhea (3.6%) and peripheral edema (3.6%). Grade 3 or 4 laboratory abnormalities ( greater than 5%) worsening from baseline included decreased absolute neutrophil count (50%), decreased phosphate (25%), elevated glucose (7%) and elevated creatine kinase (7%). Permanent discontinuation due to an adverse reaction occurred in 11% (3/28) of patients who received Pomalyst. No new safety signals were identified, and the safety of Pomalyst in Kaposi sarcoma was consistent with the known safety profile of Pomalyst in approved indications.