GSK’s Blenrep fails confirmatory Phase 3 trial, GSK withdraws the product from market

CLINICAL AND REGULATORY

ADC Elahere received FDA approval for ovarian cancer

FDA also approved Ventana FOLR1 RxDx Assay, ImmunoGen’s companion diagnostic to identify patients eligible for treatment.

FDA approved new indication for Adcetris for children with high risk Hodgkin lymphoma

Seagen announced that FDA has approved Adcetris (brentuximab vedotin) for the treatment of pediatric patients 2 years and older with previously untreated high risk classical Hodgkin lymphoma, in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide. The approval is based on data from a phase 3 study that showed patients receiving ADCETRIS in combination with standard of care dose-intensive chemotherapy AVE-PC (Adriamycin [doxorubicin], vincristine, etoposide, prednisone and cyclophosphamide) had superior event-free survival compared to patients who received standard of care chemotherapy ABVE-PC. Patients had a 59% reduction in the risk of disease progression or relapse, second cancer or death (HR 0.41 [95% Confidence Interval: 0.25, 0.67]; p=0.0002).

GSK’ Blenrep fails confirmatory Phase 3 trial in multiple myeloma and GSK withdraws the product

In the DREAMM-3 confirmatory study, Blenrep belantamab mafodotin from GSK missed the primary endpoint of PFS. The Phase 3  trial is a head-to-head study of Blenrep monotherapy versus pomalidomide in combination with dexamethasone (PomDex). The primary endpoint of PFS showed a HR of 1.03, which failed to demonstrate superiority to PomDex. The trial is a confirmatory study for the BCMA-targeted ADC, which was approved under the accelerated and conditional pathway in the US and EU, respectively. Blenrep is also being investigated in trials with combinations of other therapies, hoping to reduce corneal events while maintaining antitumor efficacy, with data expected next half. Discussions with regulatory authorities are ongoing, according to GSK. Two weeks later, FDA and GSK moved quickly to pull Blenrep from the US market, Blenrep was granted accelerated approval by FDA in August 2020 for patients with relapsed or refractory multiple myeloma. Sales of the drug in the first nine months of 2022 were $108 million. Ongoing Phase 3 trials of Blenrep, designed for earlier lines of treatment in combination with other therapies, remain active. Data from the DREAMM-7 and DREAMM-8 trials are expected in the first half of 2023. The clinical pipeline holds at least 10 more therapies targeting BCMA to treat multiple myeloma.

ADC move signals FDA ready to fix confirmatory trial process

ADC Therapeutics said in its 3Q22 financial results update that the company will not submit a BLA next year for its Cami in Hodgkin lymphoma; it has also paused material investments in the program following strong guidance from FDA that a randomized confirmatory Phase 3 trial must be well underway and ideally fully enrolled at the time of filing for the agency to consider the therapy under accelerated approval. ADC Therapeutics estimates fully enrolling such a trial would take two years. FDA’s guidance to the company could signal that the agency plans to begin taking more aggressive steps to fix problems with the accelerated approval pathway, especially now that measures that would have done so were left out of recently passed PDUFA legislation. The chief factor for success of these accelerated approval programs is timely completion of confirmatory studies, to have that trial ongoing before the application is filed, not approved. If a confirmatory trial isn’t under way before the application is submitted and ODAC recommends approval, there’s very little incentive for the company to start the trial at that point.