Good DREAMM-1 Data Keeps GSK On Track For Multiple Myeloma Filing This Year
Executive Summary
Confirmation of good trial data for GSK's promising anti-BCMA antibody-drug conjugate GSK2857916 in multiple myeloma patients keeps it in the running for eventual regulatory approval by 2020 - but it faces a formidable field of emerging rival therapies.
GlaxoSmithKline PLC confirmed plans to file its investigational anti-BCMA antibody-drug conjugate GSK2857916 with regulators by the end of this year, as further positive data from the DREAMM-1 study in relapsed/refractory multiple myeloma confirmed that nearly two thirds of patients responded to the drug after an extra year’s follow-up.
Announcing updated data from the DREAMM-1 study, published in the published in Blood Cancer Journal, GSK said "these new data confirm that 60% of patients receiving GSK2857916 achieved an overall response rate (ORR)."
"That ORR was identical to the rate previously reported in the interim analysis, after more than a year of follow-up, and demonstrates not only the potential efficacy of the medicine but the durability and depth of response," GSK said in a statement.
The number of patients achieving a complete response increased to 15% over the additional one-year follow-up period.
Relapsed/refractory multiple myeloma is a malignancy of antibody-producing plasma cells often characterized by anemia, hemorrhages, recurrent infections, and weakness.
Relapsed, or recurrent, multiple myeloma is the term for when cancer returns after treatment or after a period of remission. Since multiple myeloma does not have a cure, most patients will relapse at some point. Refractory multiple myeloma refers to when the cancer does not respond to therapy.
BCMA has become an exciting novel drug target in multiple myeloma, with a number of active programs in development.
GSK's '916 was awarded PRIME status by the European Medicines Agency (EMA) and breakthrough designation by the FDA in 2017. The UK drug maker hopes it can reach the market in mid-2020, based on results from the DREAMM-1 trial.
Still, the therapy faces stiff competition in an increasingly crowed multiple myeloma market.
bb2121 vs GSK's '916
Datamonitor Healthcare analyst Hardik Patel says Celegene's chimeric antigen receptor T-cell (CAR-T) therapy bb2121 will pose the biggest challenge to GSK's candidate.
“While its difficult to compare across trials, especially trials with small patient pools, the available evidence seems to suggest that bb2121 may be more effective than GSK's '916," Patel told Scrip.
He noted that in a Phase I trial in relapsed/refractory multiple myeloma patients who had received at least three prior lines of therapy, treatment with bb2121 at active doses (≥150 x 10^6 CAR-T cells) led to an ORR of 95.5%, a complete response (CR) rate of 50%, and a median progression free survival (PFS) rate of 11.8 months.
"GSK2857916’s DREAMM-1 study had a similar patient population, and while the median PFS was similar at 12 months, the ORR and CR rate shown by GSK2857916 of 60% and 15%, respectively was much lower than that shown by bb2121," Patel said.
"Also, the outcomes presented for GSK2857916 in patients who had received prior treatment with Johnson & Johnson's Darzalex (daratumumab) were less impressive, showing median PFS of 7.9 months and an ORR of 38.5%," he said.
"In contrast, the majority of patients in the bb2121 trial had received prior treatment with Darzalex, and the results of that trial were still overwhelmingly positive," Patel aded.
This is an important distinction, as Darzalex has become a primary treatment option for multiple myeloma patients in the earlier lines of therapy, and the majority of patients in later lines of the treatment are likely to have received at least one regimen containing the drug.
The DREAMM-1 study is small. But GSK is waiting for further data from its DREAMM-2 trial in multiple myeloma patients who have already been treated with Darzalex, which is an anti-CD38 antibody,
One advantage that GSK2857916 does hold over bb2121 is that its antibody-drug conjugate approach will likely allow the drug to be priced much more cheaply than bb2121, which is a CAR-T cell therapy.
"Assuming both drugs successfully make it to market, and the efficacy demonstrated by each drug in these early-phase trials is replicated in subsequent studies, the uptake of each drug may depend on each stakeholder’s opinion of their cost-to-benefit ratio," Patel said.
And Selinexor
Another emerging therapy in the multiple myloma market is Karyopharm Therapeutics Inc.'s selective inhibitor of nuclear export (SINE) selinexor, which is also vying for a similar patient population as that studied in GSK2857916’s pivotal DREAMM-2 trial, as well as bb2121’s pivotal KarMMa trial.
“All are examining so-called 'triple class refractory' patients who have previously received a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have received at least three prior regimens," said Datamonitor Healthcare Michael Ramirez.
However, there is reason to doubt selinexor’s competitive position against GSK2857916, as selinexor recently received an unfavorable reaction at its advisory committee meeting, where panelists voted to delay an approval decision until results from the Phase III BOSTON trial were released, which pushed a potential approval decision back to early 2020. The PDUFA date for selinexor has since shifted to July 6, as more existing data was submitted in an attempt to expedite approval, however.
“Though the data for selinexor may not look as impressive as either GSK2857916 or bb2121 - it showed an ORR of 26.2%, median prior lines of therapy = 7 - if selinexor was to end up getting approved for the highly refractory population, pricing could be an important consideration," Ramirez told Scrip.
"As a small molecule inhibitor, selinexor could conceivably be priced even cheaper than GSK2857916.
"However, even if approved, one of the doubts the FDA has around selinexor is a fairly unfavorable safety profile. This may also come into consideration in the case that all three drugs are approved for the highly refractory setting,” Ramirez said.