Ivonescimab, a revolutionary bispecific antibody developed by Akeso Biopharma, merges PD-1 immunotherapy blockade with anti-VEGF angiogenesis inhibition in one innovative formulation. Akeso's collaboration with Summit Therapeutics in December 2022 led to the licensing of ivonescimab's exclusive rights for development and commercialization in key markets, while Akeso retains control in other regions, including China.

A pivotal Phase III (HARMONi-A trial) is currently underway, assessing ivonescimab combined with chemotherapy in EGFR-mutated, locally advanced, or metastatic non-squamous NSCLC patients who have progressed after third-generation EGFR TKI treatment. Enrollment is expected to conclude in the latter half of 2024.

In May 2024, the National Medical Products Administration (NMPA) approved Ivonescimab in combination with chemotherapy for use in patients with EGFR mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have progressed after treatment with an EGFR tyrosine kinase inhibitor (TKI). This is the first approval for ivonescimab by any regulatory authority. The approval for ivonescimab was based on the trial called HARMONi-A trial. Ivonescimab is not approved by any regulatory authority in Summit’s license territories, which includes the United States, as well as, Canada, Europe, and Japan.

The first set of data in EGFR-mutant NSCLC was shared in an abstract ahead of the American Society of Clinical Oncology (ASCO) conference, showing that, a total of 322 patients were randomized (161 to the ivonescimab plus chemotherapy arm, 161 to the placebo plus chemotherapy arm). As of March 10, 2023, the median follow-up time was 7.89 months. PFS was significantly improved in the ivonescimab plus chemotherapy arm. Median PFS by IRRC was 7.06 months in the ivonescimab arm versus 4.80 months in the chemotherapy arm. The prespecified subgroup analysis showed PFS benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including in patients who progressed on the third-generation EGFR-TKIs therapy, those with brain metastases, those with EGFR mutation of deletion 19 and individuals with T790M mutation positive. The ORR were 50.6% and 35.4%, respectively. Grade ≥3 TEAEs occurred in 99 (61.5%) patients versus 79 (49.1%) patients.

KOL insights

“Ivonescimab (a PD-1 and VEGF bispecific antibody) showed benefit for patients with EGFR+ tumors not responding to TKIs.” –Expert Opinion.

“We are excited to continue to develop ivonescimab with appropriate, accelerated pace and with the intent to make a significant difference for those patients who may benefit most from new, innovative therapies in lung cancer and other solid tumors.”–Expert Opinion.

Conclusion-

NSCLC's evolution into a biomarker-driven market is evident, with EGFR standing out as a lucrative segment. In 2023, out of the 230,000 yearly NSCLC cases, approximately 15% have EGFR mutation, with a total market size of EGFR NSCLC to be approximately USD 2 billion in the US. DelveInsight's assessment suggests this figure will likely surge with the anticipated introduction of novel therapies, signaling growth in the forecast period. 

Ivonescimab plus chemotherapy showcased a notable advancement in progression-free survival (PFS) alongside a well-managed safety profile in patients previously unresponsive to EGFR-TKI treatments. Initial data presented in an abstract before the ASCO conference unveiled a median PFS of 7.06 months with ivonescimab plus chemotherapy, compared to 4.80 months for the control group. Despite this promising outcome, Summit experienced a significant downturn, with shares plummeting over 20%, marking one of the largest biotech losses before the cancer conference. Nevertheless, these findings prompted approval for the ivonescimab-chemotherapy regimen in China this month, where Akeso holds marketing rights. Summit had previously licensed the bispecific antibody in the US, Canada, EU, and Japan in 2022.