GSK Expands Jemperli Approval to Challenge Keytruda in Endometrial Cancer

Merck’s Keytruda, recently approved by the FDA for a broad first-line endometrial cancer population, now faces competition from GSK’s Jemperli. On Thursday, the FDA approved Jemperli to be used in combination with chemotherapy for patients with mismatch repair proficient (pMMR) or microsatellite-stable (MSS) tumors. This broadens Jemperli's previous approval, which was limited to a smaller group with mismatch repair deficient (dMMR) or microsatellite instability-high (MIS-H) tumors. This new approval positions Jemperli as a direct competitor to Keytruda in the endometrial cancer treatment space, regardless of biomarker status.

Hesham Abdullah, head of oncology R&D at GSK, emphasized the importance of moving quickly in the competitive checkpoint inhibitor market. Being the first in an indication provides a significant advantage, but the key question is whether Jemperli can maintain momentum against Keytruda, a PD-1 leader. Abdullah noted that GSK aimed to demonstrate the effect of Jemperli in combination with chemotherapy on overall survival.

PD-1 inhibitors are effective in dMMR tumors, with both Jemperli and Keytruda showing significant tumor progression-free survival benefits in separate phase 3 trials. However, Jemperli initially only achieved a 24% reduction in the risk of progression or death compared to chemotherapy alone, whereas Keytruda showed a 40% progression-free survival improvement in the pMMR group. Given that more than 70% of endometrial cancers are pMMR, this was a crucial metric.

With the latest approval, GSK presented data showing that Jemperli, combined with chemotherapy, could significantly extend patients' lives. In the phase 3 RUBY trial, the combination reduced the risk of death by 31% compared to chemotherapy alone, regardless of biomarker status. Specifically for the pMMR subgroup, the death risk reduction was 21%, although not statistically significant. Keytruda, on the other hand, has yet to claim an overall survival benefit and showed only a 12% death rate in the dMMR cohort and 17% in the pMMR group during an interim analysis.

Abdullah pointed out that overall survival is the gold standard for measuring the efficacy and safety of oncology drugs. This data lends additional credibility to Jemperli, especially as a newer product. He also mentioned that past clinical trials have shown varied results among PD-1 inhibitors, indicating that one inhibitor’s success does not guarantee another's. However, it remains to be seen how this advantage will translate into uptake, given the medical community's familiarity with Keytruda.

Luke Miels, Chief Commercial Officer at GSK, acknowledged Keytruda's leading position but noted a significant shift in physicians' perception of Jemperli and their willingness to try it. He suggested that potential guideline changes favoring overall survival could drive further growth. In the first quarter, Jemperli’s new patient share in first-line dMMR endometrial cancer nearly doubled to 33% compared to the end of 2023.

GSK is also exploring enhancements for Jemperli, such as combining it with the PARP inhibitor Zejula, particularly in the pMMR population. This combination is being tested in part 2 of the RUBY trial, showing stronger progression-free survival results in pMMR patients compared to Jemperli alone. However, long-term overall survival results are still pending, and there are concerns about potential adverse effects from PARP inhibitors in certain ovarian cancer patients.

Keytruda’s NRG-GY018 trial does not include a separate PARP arm, but Merck's partner AstraZeneca is testing a similar approach with its PD-L1 inhibitor Imfinzi and PARP drug Lynparza in the phase 3 DUO-E trial. Recently, Imfinzi and chemotherapy received FDA approval for dMMR tumors based on this study.

GSK anticipates that Jemperli could achieve more than £2 billion in peak sales. The company is exploring various combinations, including with TIGIT and newly licensed B7-H3 and B7-H4 antibody-drug conjugates. Abdullah highlighted the B7-H4 candidate as particularly promising for endometrial and ovarian cancers.

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