The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to GlaxoSmithKline’s investigational therapy GSK2857916 for the treatment of relapsed and refractory multiple myeloma.
The designation is for patients who received at least three prior therapies, including an anti-CD38 antibody such as Darzalex (daratumumab), and who are refractory to an immunomodulatory agent and a proteasome inhibitor. The designation follows the European Medicines Agency’s decision to grant PRIME designation to GSK2857916 for the same indication.
Breakthrough therapy and PRIME designations are expected to expedite and facilitate the development of GSK2857916 and all regulatory review processes.
“Oncology R&D at GSK is focused on developing medicines with transformational potential for patients and we are pleased that our investigational antibody-drug conjugate is the first BCMA targeting agent to receive Breakthrough Therapy and PRIME designation,” Axel Hoos, GSK’s senior vice president of oncology research and development, said in a press release. “The monotherapy data that we have seen for GSK2857916 support its transformational potential and we look forward to working with regulators as we progress the development programme.”
GSK2857916 is an engineered antibody-drug conjugate designed to target the B-cell maturation agent (BCMA). When it binds to BCMA, which is found at the surface of some healthy B-cells and myeloma cells, the drug is internalized and releases a toxic payload — monomethyl auristatin-F — which will promote cell death.
GSK2857916 is currently being evaluated in a two-part Phase 1 (NCT02064387) open-label study in patients with relapsed or refractory multiple myeloma.
In the first part of the study, patients received eight different doses of the drug, ranging from 0.03 to 3.4 mg/kg, to determine the maximum tolerated dose and optimal dose to be used in the second part of the study.
This part included 24 myeloma patients who had received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, an anti-CD38 antibody, or stem cell transplant, if eligible.
The treatment was found to be well-tolerated and safe overall, with ocular toxicity being reported as the most frequent reason to change treatment dose. Preliminary effectiveness data suggested that GSK2857916 has therapeutic potential when used at higher doses.
The findings, which supported the recent FDA and EMA decisions, were published last year in the journal Blood.
The second part of the study, which is currently ongoing, will continue to evaluate the safety and tolerability of the drug while evaluating its clinical activity. Preliminary data collected from the first 35 patients demonstrated that 60% responded to GSK2857916 monotherapy, with a median progression-free survival (PFS) of 7.9 months.
Data from this ongoing trial will be presented at the upcoming 59th annual meeting of the American Society of Hematology in Atlanta. The oral presentation is titled, “Deep and Durable Responses in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (MM) Treated with Monotherapy GSK2857916, an Antibody Drug Conjugate Against B-Cell Maturation Antigen (BCMA): Preliminary Results from Part 2 of Study BMA117159.”
“GSK plans to rapidly advance clinical trials with this promising therapy, alone and in combination with other therapies, to further investigate how GSK2857916 could benefit patients with multiple myeloma,” Hoos said.
GSK has also received orphan drug designation for GSK2857916 from the EMA and FDA to treat patients with multiple myeloma.