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Secura Bio decided to withdraw the approval of the new drug application for panobinostat for use in combination with bortezomib and dexamethasone to treat select patients with multiple myeloma.
Secura Bio has decided to withdraw the approval of the new drug application for panobinostat (Farydak) for use in combination with bortezomib (Velcade) and dexamethasone to treat patients with multiple myeloma who have previously received at least 2 regimens, including bortezomib and an immunomodulatory agent.1
The combination regimen was granted an accelerated approval from the regulatory agency in February 2015 based on data from a prespecified subgroup analysis of the phase 3 PANORAMA-1 trial (NCT01023308).2 Among 193 patients, the median progression-free survival (PFS) with the panobinostat triplet was 10.6 months (95% CI, 7.6-13.8) vs 5.8 months (95% CI, 4.4-7.1) with placebo (HR, 0.52; 95% CI, 0.36-0.76). Moreover, the addition of the HDAC inhibitor resulted in an overall response rate (ORR) of 59% vs 41% with bortezomib/dexamethasone.
This approval required further acceptable and well-controlled clinical trials to verify and demonstrate the agent’s clinical benefit in this indication. In the withdrawal submission, the pharmaceutical company noted that it is not feasible for the company to complete the required post-approval studies, as designed as part of the accelerated approval process. As such, the clinical benefit of panobinostat has not been confirmed.
“Because of the withdrawal submission, [panobinostat] will no longer be discussed at the December 2, 2021 meeting of the Oncologic Drugs Advisory Committee,” a recent press release stated. “As provided for by FDA regulations, Secura Bio anticipates FDA publishing a Federal Register notice announcing withdrawal of the approval.”
The double-blind, placebo-controlled, multicenter, phase 3 PANORAMA-1 trial enrolled a total of 768 patients with relapsed multiple myeloma who had received 1 to 3 prior lines of therapy. Study participants were randomized to panobinostat plus bortezomib/dexamethasone (n = 387) or placebo plus bortezomib/dexamethasone (n = 381). Stratification factors included prior bortezomib use and number of prior lines of therapy.
The primary end point of the trial was PFS, and key secondary end points comprised overall survival, ORR, time to response, and safety. The median follow-up for the trial was 29 months for both treatment arms.
Study participants had a median age of 63 years (range, 28-84), 53% were male, 65% were Caucasian, and 93% had an ECOG performance status of 0 to 1. Moreover, 57% of patients had undergone stem cell transplantation. The median number of prior therapies received was 1, but 48% of patients had received 2 or 3 prior lines of treatment. Prior treatment included corticosteroids (90%), melphalan (80%), thalidomide (53%), cyclophosphamide (47%), bortezomib (44%), and lenalidomide (Revlimid; 19%).
The median duration of exposure to the HDAC inhibitor was 5 months. Sixty percent of patients who received panobinostat reported a serious adverse effect (AE) vs 42% of those who did not receive the agent.
The treatment-emergent serious AEs that were most frequently reported with panobinostat included pneumonia (18%), diarrhea (11%), thrombocytopenia (7%), fatigue (6%), and sepsis (6%). Thirty-six percent of patients experienced toxicities that resulted in discontinuation of the HDAC inhibitor; these included diarrhea, fatigue, and pneumonia.
Moreover, 8% of patients on the investigative arm died vs 5% of those on the control arm. Most of these deaths were attributed to infection and hemorrhage.
Secura Bio and partners will continue to market panobinostat in other markets where it has received regulatory approval.