Bayer Withdraws US Indication for Aliqopa in Treatment of Follicular Lymphoma

Bayer is voluntarily withdrawing a new drug application for copanlisib (Aliqopa) for the treatment of adults with relapsed follicular lymphoma previously administered at least two prior systemic treatments.¹

Image credit: Bruno Coelho | stock.adobe.com

The FDA granted accelerated approval to Aliqopa in September 2017 after findings from the Phase 2 CHRONOS-1 study (NCT01660451) showed promising results. In the trial, Aliqopa was found to produce an objective response rate (ORR) of 58.7%, with a complete response (CR) rate of 14.4%, a partial response rate of 44.2%, and estimated median duration of response (DOR) of 12.2 months.²

In terms of safety, the combination was consistent with findings on the individual drugs that were previously been published, with no new safety signals identified.³

As part of the accelerated approval, Bayer was required to confirm the clinical benefit of the drug in the Phase 3 CHRONOS-4 study (NCT02626455).¹

In the Phase 3 portion of the trial, Aliqopa combined with chemoimmunotherapy regimens failed to meet the primary endpoint, as it did not significantly improve progression-free survival (PFS) compared with standard chemoimmunotherapy alone in patients with relapsed follicular lymphoma.

“Bayer is exploring access options for patients currently receiving Aliqopa who have experienced a favorable response to treatment, whose treating physician supports continuing treatment with Aliqopa, and for whom there may be no suitable alternative treatments available,” the company stated in a press release.¹ “Patients currently being treated with Aliqopa should consult their healthcare provider. No new patients should be prescribed Aliqopa.”

In the CHRONOS-4 trial, patients were enrolled with histologically confirmed relapsed indolent non-Hodgkin lymphoma, with subtypes of follicular lymphoma grades 1, 2, or 3A and small lymphocytic lymphoma with an absolute lymphocyte count of less than 5 x 109/L.

Enrollment criteria included administration of at least one and up to three lines of prior therapy, including a rituximab (Rituxan)-based chemoimmunotherapy regimen and alkylating agents.

Patients were excluded if they had histologically confirmed follicular grade 3B or transformed disease or chronic lymphocytic leukemia; if they developed resistance to Rituxan, Rituxan biosimilars, or an anti-CD20 monoclonal antibody such as obinutuzumab (Gazyva); a history of or concurrent interstitial lung disease; lymphomatous involvement of the central nervous system; or known HIV infection.

Patients were randomly assigned to receive Aliqopa combined with standard chemoimmunotherapy or chemoimmunotherapy alone, comprised of Rituxan plus bendamustine (R-B) and Rituxan plus cyclophosphamide, doxorubicin, vincristine, and prednisone or prednisolone (R-CHOP).

Phase 3 of the trial was to include approximately 520 patients, with Aliqopa analyzed at the recommended Phase 2 dose of 60 mg plus R-B. Patients were administered a maximum of six cycles of treatment.

In the Phase 3 portion, the efficacy endpoints included ORR, DOR, CR rate, time to disease progression, time to next treatment, overall survival, time to improvement in disease-related physical symptoms, time to deterioration in disease-related physical symptoms, treatment-emergent adverse effects, and disease control rate.

In the press release, Bayer said that results from CHRONOS-4 will be published “in a timely manner.”¹

Aliqopa is currently approved in the United States, China, and Taiwan as a monotherapy for the treatment of adults with relapsed follicular lymphoma.

References

1. Bayer provides update on Aliqopa (copanlisib). News release. Bayer. November 13, 2023. Accessed November 13, 2023. https://finance.yahoo.com/news/bayer-provides-aliqopa-copanlisib-150000518.html

2. FDA grants accelerated approval to copanlisib for relapsed follicular lymphoma. FDA. September 14, 2017. Accessed November 13, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-copanlisib-relapsed-follicular-lymphoma

3. Aliqopa (copanlisib) in combination with rituximab meets primary endpoint in patients with relapsed indolent non-Hodgkin’s lymphoma. News release. Bayer. October 14, 2020. Accessed October 14, 2020. https://bit.ly/3dqGE2m.