Akeso and Summit's Ivonescimab Shows Promise in Global Phase 3 Lung Cancer Trial

Akeso and Summit Therapeutics have announced positive results from their first global phase 3 trial of ivonescimab, a closely watched PD-1xVEGF bispecific antibody, in patients with previously treated EGFR-mutated nonsquamous non-small cell lung cancer (NSCLC). The HARMONi trial demonstrated that ivonescimab, when added to chemotherapy, significantly reduced the risk of disease progression or death by 48% compared to chemotherapy alone.

Impressive Efficacy in Multiple NSCLC Trials

The HARMONi trial marks the fourth positive phase 3 study for ivonescimab in NSCLC. Previously, in the China-only HARMONi-A trial, which investigated a similar post-TKI EGFR setting, ivonescimab reduced the risk of progression or death by 54%. Summit Therapeutics described the findings between the two studies as "consistent."

Cantor Fitzgerald analyst Eric Schmidt commented on the results, stating, "We think it is fairly clear that this is a drug. In each of these four trials, the data posted by ivonescimab appear differentiated from and superior to PD-1 therapy."

Global Trial Results and Regulatory Plans

The HARMONi trial included patients who had progressed following treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI). While overall survival data remains immature, Summit reported a positive trend favoring ivonescimab, with a preliminary 21% reduction in the risk of death.

Based on these results, Summit intends to seek approval from the FDA. However, the company stated it will "consider the timing" of the filing based on discussions with the agency, suggesting that more mature overall survival data from the Western patient population may be required.

Approximately 38% of HARMONi participants were randomized from Western countries, addressing concerns about the drug's efficacy in non-Asian populations. Summit noted that this enrollment rate is consistent with past multiregional phase 3 trials in EGFR-mutated NSCLC.

Market Potential and Future Outlook

While the post-TKI EGFR-mutant NSCLC indication represents a relatively small market, with annual sales potential estimated between $500 million to $1 billion, ivonescimab's success in this trial may have broader implications. The drug's performance in the ongoing HARMONi-2 trial, where it topped Merck & Co.'s Keytruda in first-line, PD-L1-positive NSCLC, suggests potential in larger NSCLC populations with market opportunities exceeding $10 billion annually.

As the pharmaceutical industry closely watches ivonescimab's development, these latest results from the HARMONi trial provide further evidence of the drug's potential to significantly impact the treatment landscape for NSCLC patients.