Summit shrugs off survival miss with its VEGF bispecific

Summit Pharma has revealed that a second pivotal trial of its Akeso-partnered PD-1xVEGF bispecific ivonescimab has failed to show an improvement in overall survival in a lung cancer trial.

New topline data from the phase 3 HARMONi study demonstrated that ivonescimab in combination with chemotherapy reduced the risk of disease progression or death by 48% compared to chemo alone when used as a second-line or later therapy for EGFR-mutant non-small cell lung cancer (NSCLC), but a 21% improvement in survival did not meet the threshold for statistical significance.

Last month, shares in Summit lost more than a third of their value after Akeso revealed OS data from the Chinese HARMONi-2 trial comparing ivonescimab to MSD's PD-1 inhibitor Keytruda (pembrolizumab), both given on top of chemo, which showed a 22% reduction in the risk of death that also failed to cross the significance threshold.

Earlier results from the study, including a 49% improvement in progression-free survival (PFS), were reported at last year's WCLC congress and caused Summit's share price to surge to a near 52-week high of almost $32.

This time, investors' reaction was muted – at least at the time of writing, when Summit's stock was only down a point or two at a little under $26 – perhaps suggesting that nervousness over the survival data had already been factored in. After all, it's not uncommon that an initial trend in OS can translate to a significant improvement with longer follow-up.

In a statement, Summit pointed to the consistency in the results between the Chinese and international studies, and noted that HARMONi focuses on a patient population where PD-1 inhibitors "have previously been unsuccessful" at showing improvement in both OS and PFS.

There are no current FDA-approved regimens that have demonstrated a statistically significant improvement in OS in second-line or later EGFR-positive NSCLC, the company said, adding that it is considering filing for approval of ivonescimab on the strength of the data.

The timing of that filing has yet to be determined, however, and will likely depend on discussions with the FDA, which has previously said it would need a significant OS improvement to support a marketing application.

Co-chief executive Dr Maky Zanganeh said: "Our conviction in the promise that this therapy holds for patients continues to be validated: we believe that ivonescimab has the potential to make a meaningful difference for the betterment of patients' lives."

Summit licensed rights to ivonescimab in a $5 billion deal – including a whopping $500 million upfront – in 2022. The drug has already been approved in China for EGFR-positive NSCLC that has progressed after treatment with an EGFR inhibitor.