Blenrep combinations for myeloma now under review in EU
EMA accepts GSK's application for marketing approval to treat RRMM
A committee of the European Medicines Agency (EMA) has accepted for review GSK’s marketing authorization application for Blenrep (belantamab mafodotin) to be used as part of a combination treatment for people with relapsed or refractory multiple myeloma (RRMM).
The Committee for Medicinal Products for Human Use (CHMP) will now examine all data filed and recommend whether or not Blenrep should be approved for use alongside bortezomib plus dexamethasone (BorDex), or with pomalidomide plus dexamethasone (PomDex).
“Today’s milestone reinforces the potential for Blenrep to redefine outcomes for patients with multiple myeloma at or after first relapse,” Hesham Abdullah, GSK’s senior vice president and global head of oncology research and development, said in a company press release.
Blenrep as a monotherapy — to be used by itself rather than as a combination treatment — has had a complicated history in both the European Union, where it had received conditional approval, and in the U.S., where it was granted accelerated approval. In both regions, however, the monotherapy has since been withdrawn from the market. Now, however, based on positive early data from two Phase 3 trials, the company is trying a new strategy in which Blenrep instead would be used in combination with already approved medications.
New strategy for Blenrep approval based on DREAMM trials
Earlier this year, Blenrep was pulled out of the European market, where it had been granted conditional approval to treat adults with RRMM who had received at least four previous lines of treatment, after a non-renewal by regulators. Previous treatment would have included a proteasome inhibitor, an immunomodulatory treatment, and an anti-CD38 monoclonal antibody.
Conditional, or accelerated, approval allows a medication to be brought to market with less complete clinical trial data than normally is needed for full approval. It is granted in cases in which the treatment’s early availability is believed to outweigh potential risks. However, full approval is dependent upon data from confirmatory trial(s) demonstrating the therapy’s benefits in patients.
The European Commission’s decision against renewing the therapy’s conditional approval followed a CMHP opinion that DREAMM-3 (NCT04162210), a confirmatory Phase 3 trial, failed to show Blenrep’s superiority over standard care at prolonging life without signs of disease progression, known as progression-free survival.
A similar withdrawal decision had been made in 2022 in the U.S., where Blenrep had been granted accelerated approval two years earlier as a fifth-line treatment for adults with RRMM.
After withdrawing the treatment as a monotherapy, GSK mapped out plans for a reworked approach wherein Blenrep is used in combination with already approved medications. This approach was based on positive interim readouts from two Phase 3 trials, DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623).
We are working to bring Blenrep to patients as quickly as possible given the high unmet need and the clinically robust effects of the Blenrep combinations in the DREAMM-7 and DREAMM-8 Phase [3] head-to-head trials.
The company is now moving forward to advance its combination treatment strategy.
“We are working to bring Blenrep to patients as quickly as possible given the high unmet need and the clinically robust effects of the Blenrep combinations in the DREAMM-7 and DREAMM-8 Phase [3] head-to-head trials,” Abdullah said.
Combination treatment found to reduce survival in trials
Multiple myeloma begins in abnormal plasma cells, a type of immune cells. The cancer can be difficult to treat and is often refractory, meaning plasma cells grow in number despite treatment, or relapsing, when it comes back after treatment.
Blenrep contains an antibody designed to bind to BCMA, a protein found on the surface of plasma cells. The antibody is linked to a toxic chemical called auristatin F. Upon binding, the antibody helps deliver auristatin F into plasma cells, killing them.
Interim data from the ongoing DREAMM-7 and DREAMM-8 trials showed statistically and clinically meaningful improvements in progression-free survival with Blenrep when used as part of a combination treatment relative to standard care.
This meant that both studies met their main goals. In both trials, Blenrep was administered through an into-the-vein, or intravenous, infusion every three weeks.
In the DREAMM-7 study, 494 adults with RRMM who had received at least one line of treatment were randomly assigned to receive either Blenrep plus BorDex or Johnson & Johnson Innovative Medicine’s Darzalex (daratumumab) plus BorDex.
The results showed that the Blenrep combo reduced, by 59%, the risk of cancer progression or death compared with Darzalex plus BorDex, with a median progression-free survival of 36.6 versus 13.4 months.
The DREAMM-8 trial included 302 RRMM adult patients who had been treated with at least one prior therapy line, including lenalidomide (sold as Revlimid, with generics available).
Data demonstrated that Blenrep plus PomDex treatment was associated with a nearly 50% lower risk of progression or death relative to a standard combination of Takeda’s bortezomib (sold as Velcade and generics) plus PomDex.
Both trials showed that Blenrep combinations provided better and longer-lasting responses than did standard-of-care treatment across all secondary efficacy measures. Side effects were similar to what is already known for the individual medications used.
Moving forward, CHMP will review GSK’s application and make a recommendation to the European Commission on whether or not to grant the authorization.
About the Author
