Akeso, Summit's Keytruda win sparks 'explosive' interest at ASCO. What does Merck think?

A groundbreaking development in the field of oncology has sparked significant conversation ahead of the American Society of Clinical Oncology’s (ASCO) annual meeting. Ivonescimab, a bispecific antibody from China, has reportedly outperformed Merck & Co.'s renowned PD-1 inhibitor, Keytruda, in a direct phase 3 trial involving non-small cell lung cancer (NSCLC) patients.

Ivonescimab, created by Chinese biotech company Akeso and licensed to Summit Therapeutics in the U.S. under a potentially $5 billion agreement, showed a noteworthy increase in patients' progression-free survival (PFS) time compared to Keytruda in the HARMONi-2 trial. This study focused on patients with tumors expressing positive PD-L1. This marks the first instance where a single drug has surpassed Keytruda in a head-to-head phase 3 NSCLC trial.

Summit Therapeutics’ CEO, Bob Duggan, heralded this result as a potential paradigm shift in cancer treatment. As analysts work to understand the financial consequences, the biopharmaceutical community eagerly anticipates the detailed data. However, Merck's perspective on this development is cautious. Merck’s Chief Medical Officer, Eliav Barr, acknowledges the potential benefits for patients but highlights the challenge of demonstrating an overall survival (OS) advantage, which is critical for regulatory and payer approval.

Although Merck and Eisai's combination of Keytruda and the VEGF-targeting kinase inhibitor Lenvima reduced the risk of disease progression or death by 22% in the LEAP-007 trial, it did not achieve a positive overall survival outcome. Barr emphasizes that achieving overall survival superiority will be crucial for ivonescimab to gain FDA approval for first-line NSCLC treatment.

The defeat of Keytruda in this context is significant, given its $25 billion sales in 2023 across various applications. The oncology community, including Takeda’s new oncology unit head, P.K. Morrow, is keenly awaiting more detailed results from Summit Therapeutics.

Keytruda was initially approved by the FDA for treating PD-L1-positive NSCLC in 2016. However, it is now primarily used as a monotherapy for patients with high PD-L1 expression. For those with lower PD-L1 expression, Keytruda is typically combined with chemotherapy. Therefore, ivonescimab will need to demonstrate superiority over both Keytruda alone and its combination with chemotherapy in these settings.

Despite the promising results from the HARMONi-2 trial, conducted exclusively in China, there is widespread agreement that this alone may not suffice for U.S. filing, especially for a prevalent condition like NSCLC. Richard Pazdur, the FDA’s oncology chief, emphasized the importance of diverse clinical data during the ASCO meeting. The FDA prefers to review datasets that span multiple trial sites to ensure consistency and reliability, a confidence not extended to data from a single-country study.

Jefferies analysts suggested that the observed PFS benefit in the HARMONi-2 trial might be influenced by the Chinese patient population, noting that past trials indicated better outcomes for anti-VEGF treatments in Asian patients compared to non-Asian populations. However, Summit Therapeutics reported that ivonescimab's PFS benefit was consistent across various patient subgroups, including those with low and high PD-L1 expression, different tumor types, and high-risk patients. Further detailed results are expected to be presented at an upcoming medical conference.

Overall, while ivonescimab’s initial success presents an intriguing development in the fight against NSCLC, its journey towards FDA approval and broader acceptance remains contingent on demonstrating a clear overall survival benefit and reproducibility across diverse patient populations.