FDA Grants Breakthrough Designation to Treatment for Kaposi Sarcoma

Celgene’s pomalidomide (Pomalyst) has been granted Breakthrough Therapy designation by the FDA for the treatment of patients with previously-treated HIV-positive Kaposi sarcoma (KS) and patients with HIV-negative KS, according to a press release.

KS is a cancer caused by an associated herpesvirus that develops from the cells that line lymph or blood vessels. The disease most commonly affects individuals with HIV, for whom there are currently no approved therapies in the refractory or chemotherapy-intolerant setting.

Pomalidomide, a thalidomide analogue, is currently indicated in combination with dexamethasone for patients with multiple myeloma who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor, and who have demonstrated disease progression on or within 60 days of completion of the last therapy.

The designation was granted on the basis of the results of a clinical study performed under a Cooperative Research and Development Agreement, which evaluated pomalidomide in patients with KS, with or without HIV infection, many of whom had received prior cytotoxic chemotherapy.

In the study, which was published in the Journal of Clinical Oncology, patients received an initial dosage level of 5 mg once per day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and aspirin 81 mg once per day thromboprophylaxis. A total of 22 patients were included in the trial: 68% were HIV-infected, 77% had advanced disease, and 86% had previous KS therapy, excluding antiretroviral therapy.

Overall, the data showed that 16 patients responded to treatment (73%; 95% CI, 50% to 89%), 9 of 15 patients with HIV and all 7 patients without HIV, with a median time to response of 4 weeks. The study showed no impairment during therapy and improved satisfaction with appearance at the end of therapy. Additionally, significant increases in CD4+ and CD8+ cells were seen in patients with and without HIV, together with a transient increase in KS-associated herpesvirus viral load at week 4, according to the results.

The findings suggest that pomalidomide is well tolerated and active in KS regardless of HIV status. Currently, unmet needs for KS include therapies that are oral, anthracycline sparing, and deliverable in resource-limited settings, the study authors noted.

“The encouraging news of the FDA Breakthrough Therapy designation for Pomalyst in Kaposi sarcoma reflects the urgency in accelerating the development of therapies to address diseases of this type,” Jay Backstrom, MD, chief medical officer for Celgene, said in a statement. “We will continue to work closely with the agency to move this program forward for patients with this rare and serious cancer.”

Celgene plans to submit a supplemental New Drug Application for pomalidomide in this indication by the end of 2019, according to the release.

References

Celgene Corporation Announces Pomalyst Granted Breakthrough Therapy Designation from FDA for HIV-Positive and Negative Kaposi Sarcoma [news release]. Celgene. https://ir.celgene.com/press-releases/press-release-details/2019/Celgene-Corporation-Announces-POMALYST-Granted-Breakthrough-Therapy-Designation-from-FDA-for-HIV-Positive-and-Negative-Kaposi-Sarcoma/default.aspx. Accessed May 13, 2019.

Polizzotto MN, Uldrick TS, Wyvill KM, et al. Pomalidomide for symptomatic Kaposi’s sarcoma in people with and without HIV infection: a phase I/II study. Journal of Clinical Oncology. 2016. DOI: 10.1200/JCO.2016.69.3812