GSK files multiple myeloma drug with FDA after phase 2 success


GSK has filed for FDA approval of its potential first-in-class multiple myeloma drug belantamab mafodotin for relapsed/refractory multiple myeloma on the basis of a set of strong results from a phase 2 trial.

Also known as GSK2857916, belantamab mafodotin is an antibody-drug conjugate with the antibody component targeting the B-cell maturation antigen monoclonal antibody, linked to the cytotoxic agent auristatin F via a non-cleavable linker.

Latest results from the DREAMM-2 trial show an overall response rate (ORR) of 31% with a 2.5 mg/kg regimen and no new safety signals in heavily pre-treated patient populations who were refractory to an immunomodulatory drug and a proteasome inhibitor and were refractory or intolerant to an anti-CD38 antibody.

The drug’s Breakthrough Therapy status with the FDA, reserved for medicines that could improve care standards in serious diseases, suggests that a faster six-month review period could be on the cards and a potential launch midway through 2020 if the review goes well.

Patients in the trial received a median of seven prior lines of treatment, were refractory to an immunomodulatory drug and a proteasome inhibitor and were refractory and/or intolerant to an anti-CD38 antibody. The median duration of response has not been reached at six months of follow-up.

While there are a host of drugs already approved for multiple myeloma, patients can usually expect to live for around three years after diagnosis with the cancer of plasma cells and bone marrow, although some can live for up to a decade.

With these results from the open label study GSK hopes to become the first anti-BCMA agent available in the US.

Thirty of the 97 patients (31%) in the 2.5 mg/kg cohort achieved an overall response. Of these responders, 18 patients achieved a very good partial response or better, including three patients with stringent complete or complete responses. Overall survival in patients achieving a response was not reached in the six-month follow-up period.

The safety and tolerability profile was consistent with previously reported data on belantamab mafodotin. The three most commonly reported Grade 3 or 4 adverse events in the 2.5 mg/kg arm were keratopathy (27%), thrombocytopenia (20%) and anemia (20%). Keratopathy is characterised as changes in the corneal epithelium as seen on an eye examination which can manifest with or without symptoms.

Corneal events leading to treatment discontinuation affected 1% of patients in the 2.5 mg/kg cohort.

GSK is also testing belantamab mafodotin as a third-line monotherapy in relapsed/refractory multiple myeloma and in combination with standard and novel treatments in the first and second line setting.

Johnson & Johnson's Janssen unit is another company trying to target BCMA - its CAR-T therapy JNJ-68284528 which works on the receptor was granted Breakthrough Therapy status in multiple myeloma by the FDA earlier this month.

AbbVie has also been trying to develop its Venclexta (venetoclax) in multiple myeloma but had to stop recruiting to the BELLINI trial after a safety scare earlier this year.

The latest news from Venclexta, revealed at the American Society of Hematology conference earlier this month, is that it seems to work safely in a group of myeloma patients who have a certain set of mutations.