Another PD-1 antibody is about to hit the U.S. market, following the FDA’s accelerated approval of dostarlimab (TSR-042) from partners Anaptysbio Inc. and Glaxosmithkline plc. But dostarlimab, branded Jemperli, will be only one of two PD-1 drugs indicated for endometrial cancer, going up against Merck & Co. Inc.’s Keytruda (pembrolizumab). The medicine was cleared for use in patients with recurrent or advanced DNA mismatch repair (dMMR) deficient disease whose cancer has progressed on or following prior treatment with a platinum-containing chemotherapy.

The approval was granted under the FDA’s Real-Time Oncology Review pilot program. Timing for the product’s initial availability and pricing weren’t immediately clear.

“Today’s approval of Jemperli is evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” said Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Endometrial cancer is the most common gynecologic malignancy in the U.S. with an increasing prevalence the FDA said. About 75% of endometrial cancers are diagnosed early on and are typically curable with surgery. Women with advanced and recurrent endometrial cancer, however, have limited treatment options following front-line standard therapy with a platinum-containing chemo regimen. About 25% to 30% of patients with advanced endometrial cancer have dMMR tumors, the agency said.

An FDA decision on the medicine, which received both priority review and breakthrough therapy status, initially had been expected in the fourth quarter of 2020. But Anaptysbio reported in a November 10-Q filing that the FDA was unable to complete a manufacturing site inspection, and no action was taken.

Supportive evidence

Approval was based on data from a single-arm, multi-cohort Garnet study, which, in an updated analysis presented at the Society of Gynecologic Oncology meeting in April 2020, showed an objective response rate (ORR) of 42.3%. Overall, 13% of patients had a complete response and 30% had partial responses. Of those that responded to the medicine, 93.3% demonstrated a duration of response of 6 months or more. After a median follow-up of 14.1 months, the median duration of response was not reached (2.6-22.4+), GSK said.

Further data presented at the ESMO 2020 virtual meeting showed the drug induced antitumor activity in patients advanced or recurrent dMMR and mismatch repair proficient (MMRp) endometrial cancer. Treatment with dostarlimab resulted in an ORR of 44.7% in patients with dMMR disease, with 11 complete responses and 35 partial responses, and an ORR of 13.4% in those with MMRp disease, with three complete responses and 16 partial responses.

Common side effects of Jemperli, according to the FDA, include fatigue, nausea, diarrhea, anemia and constipation. Jemperli can also cause serious conditions known as immune-mediated side effects, including inflammation of healthy organs, the regulator noted in an announcement of the approval.

Dostarlimab is also being tested in the phase III RUBY trial, enrolling women with recurrent or primary advanced endometrial cancer in combination with standard-of-care chemotherapy. Additional studies evaluating the combination with other therapeutic agents against advanced solid tumors and metastatic cancer also are ongoing.

Rewards ahead

Anaptysbio earned a $20 million milestone payment triggered by the approval under its original cancer antibody collaboration with Tesaro Inc. in 2014. In the time since Tesaro was acquired by GSK in a $5.1 billion deal, it also received milestone payments of $10 million and $5 million for the FDA’s and EMA’s acceptances of the BLA and marketing authorization application filings for Jemperli, respectively. Payments totaling an additional $45 million will be due to Anaptysbio upon the achievement of future regulatory milestones for Jemperli in the U.S. and Europe, the San Diego-based company said Thursday.

In October 2020, Anaptysbio and GSK amended the collaboration to increase royalties due to Anaptysbio for dostarlimab, which will now receive 8% to 25% of global net royalties, with 8% due on sales below $1 billion and 12% to 25% due on net sales topping $1 billion. The potential milestone payments totaling up to $1.1 billion remain unchanged.

Dostarlimab also is under review in Europe, with a decision expected soon. The EMA’s Committee for Medicinal Products for Human Use issued a positive recommendation Feb. 26. Formal European Commission approval would trigger a $10 million payment to Anaptysbio. Shares of Anaptysbio (NASDAQ:ANAB) rose 0.6% to $22.82 on Thursday. U.S.-listed shares of GSK (NYSE:GSK) fell 1.5% to $37.68.

Still pending

Despite worries that COVID-19-related travel restrictions would severely interrupt the FDA’s approval process during 2020, the year actually saw one of the highest approval rates for new molecular entities. And, despite the pandemic, the agency has been able to hit most of its PDUFA dates.

However, Anaptysbio and GSK had company in experiencing a delay, with a handful of review outcomes still pending, largely due to travel-related restrictions. A decision for Revance Therapeutics Inc.’s BLA for daxibotulinumtoxinA for moderate to severe glabellar lines, which had a PDUFA date of Nov. 25, was deferred due to COVID-19. As was Mylan Inc.’s MYL-14020, a bevacizumab biosimilar for solid tumors partnered with Biocon Ltd. That drug had had a PDUFA date of Dec. 27.

A decision on osteoarthritis drug tanezumab, from Pfizer Inc. and Eli Lilly and Co., also had been expected in the fourth-quarter, with timing seeming even more uncertain following a lengthy joint adcom meeting for the drug in March.

A decision is also overdue on Arbor Pharmaceuticals Inc.’s AR-19 (amphetamine sulfate) for attention deficit hyperactivity disorder, which had a PDUFA date of Nov. 15, though an FDA advisory committee voted against the application in October.

Most recently, Mallinckrodt plc reported that an FDA decision on its regenerative skin tissue therapy, Stratagraft, which had an anticipated PDUFA date of Feb. 2, experienced an inspection-related delay.