The U.S. Food and Drug Administration (FDA) has granted GlaxoSmithKline, one of the world’s leading research-based pharmaceutical and healthcare companies, Breakthrough Therapy Designation for its antibody-drug conjugate GSK2857916 used as a monotherapy in patients with multiple myeloma who have failed at least three prior lines of therapy, including an anti-CD38 antibody and are refractory to a proteasome inhibitor and an immunomodulatory agent.
GSK2857916 is a humanised anti B-cell maturation agent (BCMA) in which an afucosylated monoclonal antibody is conjugated, via non-cleavable linker, to the auristatin analogue and microtubule inhibitor monomethyl auristatin phenylalanine monomethyl auristatin-F (MMAF). The drug linker technology in-licensed from Seattle Genetics.
The anti-BCMA antibody moiety of anti-BCMA ADC GSK2857916 selectively binds to the BCMA on tumor cell surfaces. Following internalization, MMAF binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and induces tumor cell apoptosis. In addition, GSK2857916 induces antibody-dependent cellular cytotoxicity (ADCC). In turn, this results in the inhibition of cellular proliferation in tumor cells that overexpress BCMA.
Phase II trials
GSK2857916 is currently in phase I clinical development (NCT02064387) in patients with relapsed/refractory multiple myeloma and other advanced haematologic malignancies expressing BCMA.
Earlier this year, in October, the European Medicines Agency (EMA) granted PRIME designation to GSK2857916 for the treatment of relapsed and refractory multiple myeloma patients whose prior therapy included a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.
GSK2857916 has also received orphan drug designation from the EMA and FDA for multiple myeloma.
PRIME and Breakthrough Therapy Designations
The PRIME and Breakthrough Therapy Designations are based on results from a phase I open-label, dose escalation and expansion study in patients with relapsed/refractory multiple myeloma, irrespective of BCMA expression.
“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, Senior Vice President Oncology R&D, at GlaxoSmithKline noted.
“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. 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 program,” Hoos added.
|Breakthrough Therapy Designation||PRIME designation||Orphan designation|
|Designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). Drugs that receive breakthrough therapy designation are eligible for all features of FDA’s Fast Track Program. ||Offered by the European Medicines Agency (EMA) to enhance support for the development of medicines that target an unmet medical need. It is based on enhanced interaction between sponsor companies and the EMA to optimize development plans and speed up evaluation so these medicines can reach patients earlier. ||Granted for therapies intended to treat conditions that affect fewer than 200,000 people in the U.S. The designation qualifies the sponsor of the drug for various development incentives of the Orphan Drug Act, including tax credits for qualified clinical testing.|
In Europe, sponsors who obtain Orphan Designation for a potential new medicine benefit from a range of incentives, including protocol assistance, access to the centralized procedure, market exclusivity and fee reductions.