FDA starts review of Summit's VEGFxPD-1 bispecific

Summit Therapeutics has moved ahead in the race to bring a therapy targeting both VEGF and PD-(L)1 to market, after the FDA started a review of its ivonescimab drug for lung cancer.

The US regulator has started the clock ticking on its appraisal of ivonescimab in combination with chemotherapy for patients with EGFR-mutated non-small cell lung cancer (NSCLC) previously treated with targeted inhibitors, with an action date of 14th November.

Bispecific VEGFxPD-(L)1 drugs have emerged as one of the hottest topics in oncology in the last couple of years, after ivonescimab – originally developed by China's Akeso – showed it was more effective at extending survival in PD-L1-positive NSCLC than MSD's $30 billion PD-1 inhibitor blockbuster Keytruda (pembrolizumab), at least in a Chinese patient population.

While results were less impressive in international patients – and after some pushback from the FDA – the agency has now agreed to start its review of ivonescimab based mainly on results of the phase 3 HARMONi trial, which compared ivonescimab plus chemo to chemo alone in patients previously treated with a third-generation EGFR inhibitor like AstraZeneca's Tagrisso (osimertinib).

Summit said in a statement that the FDA will review the "overall results" of HARMONi and has said it will "perform a complete review of the accepted and filed application," including planned mid-cycle and wrap-up meetings.

Expectations for ivonescimab took a further dive after Akeso reported the results of the HARMONi-2 trial, which was unable to demonstrate a statistically significant improvement in overall survival compared to Keytruda, both given on top of chemo, in a Chinese-only patient population with previously untreated, PD-L1-positive NSCLC.

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.

The initial data with ivonescimab prompted a series of licensing deals, mainly involving pharma multinationals and Chinese biotechs that have pioneered the development of VEGFxPD-(L)1 assets.

At this year's JPM Healthcare conference, AbbVie signed a $5.6 billion licensing agreement for a candidate developed by RemeGen, while earlier deals have involved Pfizer and 3SBio ($6 billion), MSD and LaNova Medicines ($3.3 billion), and Bristol Myers Squibb with BioNTech's Chinese unit Biotheus ($11 billion).