FDA approves Pomalyst as first new Kaposi sarcoma treatment in 20 years
The FDA granted accelerated approval to pomalidomide for treatment of two forms of Kaposi sarcoma.
The approval applies to use of pomalidomide (Pomalyst, Bristol-Myers Squibb) by patients with AIDS-related Kaposi sarcoma whose disease has become resistant to highly active antiretroviral therapy, or by patients with Kaposi sarcoma who are HIV-negative.
Pomalidomide — a thalidomide analogue already approved for use with dexamethasone for treatment of certain patients with multiple myeloma — is the first new treatment option for Kaposi sarcoma in more than 20 years.
“Patients with Kaposi sarcoma have had few options to manage their disease for 2 decades,” Diane McDowell, MD, vice president for hematology global medical affairs for Bristol-Myers Squibb, said in a company-issued press release. “We’re excited that the additional research into Pomalyst in this rare disease area has resulted in our ability to provide a much-needed oral treatment option for patients.”
The FDA based the approval on results of the phase 1/phase 2 12-C-0047 trial.
The open-label, single-arm trial included 28 adults with symptomatic Kaposi sarcoma. Most patients had advanced disease, and the 18 HIV-positive patients in the trial continued concomitant highly active antiretroviral therapy.
All patients received pomalidomide dosed at 5 mg once daily for 21 days of each 28-day cycle. Treatment continued until disease progression or unacceptable toxicity.
Study protocol excluded patients with symptomatic pulmonary or visceral Kaposi sarcoma, history of venous or arterial thromboembolism or procoagulant disorders. Patients received thromboprophylaxis with aspirin dosed at 81 mg once daily throughout therapy.
Investigator-assessed overall response rate served as the primary endpoint.
Researchers reported an ORR of 71% (95% CI, 51-87). Four patients (14%) achieved complete response and 16 patients (57%) achieved partial response.
Median time to first response was 1.8 months (range, 0.9-7.6) and median duration of response was 12.1 months (95% CI, 7.6-16.8). Ten (50%) of the patients who responded to treatment maintained a response for more than 12 months.
“Pomalyst has shown positive results in [patients with Kaposi sarcoma], regardless of their HIV status,” lead researcher Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch within NCI’s Center for Cancer Research, said in the release. “Also, it provides a therapy that is taken orally and works by a different mechanism of action than the cytotoxic chemotherapy drugs generally used to treat Kaposi sarcoma.”
Pomalidomide exhibited a safety profile consistent with that observed in other approved indications.
The most common adverse events 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 grade 4 adverse reactions included maculopapular rash (3.6%), diarrhea (3.6%) and peripheral edema (3.6%).
Grade 3 or grade 4 laboratory abnormalities included decreased absolute neutrophil count (50%), decreased phosphate (25%), elevated glucose (7%) and elevated creatine kinase (7%).
Three patients (11%) discontinued treatment due to adverse events.
The FDA previously granted breakthrough therapy designation and orphan drug designation to pomalidomide for these indications.
A boxed warning notes pomalidomide can cause fetal harm and is contraindicated for pregnant women.