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Akeso, Inc

康方生物

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  • New Indication Approval (April 25, 2025): Approved by China’s National Medical Products Administration (NMPA) as a monotherapy for the first-line treatment of PD-L1 positive locally advanced or metastatic non-small cell lung cancer (NSCLC).
  • Previous Approval (May 2024): Initially approved in China for the second-line treatment of NSCLC.
  • Rapid Progression: The swift approval from second-line to first-line treatment within less than a year underscores its excellent efficacy.

Superior Efficacy (HARMONi-2 Study):

  • Head-to-Head Comparison: The HARMONi-2 study directly compared Ivonescimab (AK112) with Pembrolizumab (Keytruda, K药), a leading PD-1 inhibitor, as a first-line treatment for PD-L1 positive NSCLC.
  • Presentation: The study data was presented by Professor Zhou Caicun at the 2024 World Lung Cancer Congress, receiving significant acclaim.
  • Key Results (398 patients, 8.6 months follow-up):
    • Progression-Free Survival (PFS): Ivonescimab significantly improved median PFS by 91.4% compared to Keytruda (11.14 months vs. 5.82 months). AK112 reduced the risk of disease progression or death by 49%.
    • Objective Response Rate (ORR): Ivonescimab showed a higher ORR (50.0%) compared to Keytruda (38.5%).
    • Disease Control Rate (DCR): Ivonescimab also demonstrated a higher DCR (89.9%) compared to Keytruda (70.5%).
  • Uniqueness: Ivonescimab is currently the only anti-cancer drug globally to demonstrate superior efficacy over Keytruda in a head-to-head Phase III monotherapy clinical trial, in terms of both ORR and PFS.

Mechanism of Action (“Next-Generation” Immunotherapy):

  • Bispecific Antibody: Unlike traditional monoclonal antibodies, Ivonescimab is a bispecific antibody. It has two different antigen-binding regions sharing a common antibody constant region, allowing it to recognize two different tumor-associated antigens (PD-1 and VEGF).
  • Synergistic Effect: This dual targeting is hypothesized to offer a more potent and coordinated anti-tumor effect compared to single antibodies or combinations of two separate monoclonal antibodies.
  • Future Potential: The combination of PD-1 and VEGF targeting suggests that AK112 has the potential to replace traditional combination therapies involving PD-1 inhibitors and anti-VEGF drugs (like Avastin/Bevacizumab).

Safety Profile:

  • While Ivonescimab showed slightly higher rates of Grade 3 (severe) side effects compared to Keytruda, primarily attributed to its VEGF inhibition, the rates of serious adverse events were relatively similar.

Future Outlook:

  • Overall Survival (OS) data from the HARMONi-2 study is still maturing, but based on the strong PFS advantage, an impressive OS benefit is anticipated.
  • With ongoing global clinical studies, Ivonescimab is expected to continue bringing more positive surprises to cancer patients.