Summit's inhibitor outperforms Keytruda in lung cancer trial

Ivonescimab, a drug developed by Summit Therapeutics, has demonstrated significant efficacy in reducing the risk of lung cancer progression or death when compared to MSD's widely-used drug Keytruda (pembrolizumab). Data from a Phase III clinical trial, presented at the World Conference on Lung Cancer (WCLC) in San Diego on 8 September, revealed that ivonescimab extended progression-free survival (PFS) among patients with advanced non-small cell lung cancer (NSCLC).

The HARMONi-2 study, a Phase III trial, involved 398 patients in China who had PD-L1-positive, advanced NSCLC. Participants were randomly assigned to receive either ivonescimab or Keytruda as their initial post-diagnosis treatment. Ivonescimab, a bispecific antibody targeting both PD-1 and VEGF, showed a median PFS of just over 11 months, compared to nearly six months for those treated with Keytruda. This 5.3-month increase in median PFS equated to a statistically significant 49% reduction in the risk of cancer progression or death.

Summit Therapeutics had previously announced in May 2024 that the HARMONi-2 trial met its primary endpoint, a claim now corroborated by the detailed data. Following this announcement, the biotech firm's stock price experienced a significant surge, and its market capitalisation now stands at $13.55 billion. The trial's results are particularly notable as no previous Phase III trials in NSCLC have shown such a substantial improvement in PFS in a direct comparison with Keytruda.

Keytruda, a PD-1 checkpoint inhibitor, achieved $25 billion in revenue last year, according to MSD's financial reports. This figure is projected to rise, with GlobalData estimating that Keytruda will generate $33.7 billion in 2028, the year when its key patents are due to expire.

Summit acquired ivonescimab in December 2022 by paying $500 million to the China-based company Akeso for commercial rights in regions including the US and Europe. If approved, GlobalData analysis suggests that ivonescimab could achieve sales of up to $1.7 billion by 2030.

Despite the promising results, the HARMONi-2 study also identified a higher incidence of severe side effects in patients treated with ivonescimab compared to those receiving Keytruda. Among the ivonescimab group, 29.4% experienced treatment-related adverse events (TRAEs) of grade 3 or above, compared to 15.6% in the Keytruda group. These adverse events included abnormal levels of protein in the urine and other laboratory-detected abnormalities.

Following the HARMONi-2 results, Summit announced plans to launch another Phase III trial, HARMONi-7, in early 2025. This upcoming study will compare ivonescimab monotherapy to Keytruda monotherapy in patients with metastatic NSCLC whose tumours exhibit high PD-L1 expression.

Summit CEO Robert Duggan commented on the study's outcome, stating, "This is a historic moment for ivonescimab, Team Summit, our partners at Akeso, and most importantly, we believe this is the beginning of a landscape shift for treatment options for patients living with cancer."

In summary, Summit Therapeutics' ivonescimab has shown a potential to transform the treatment landscape for advanced NSCLC, offering a significant improvement in progression-free survival compared to the established drug Keytruda. While the drug's higher rate of severe side effects warrants careful consideration, the promising efficacy results have paved the way for further clinical investigation and potential future approvals.