Akeso and Summit Therapeutics' Lung Cancer Drug: Navigating Data Skepticism and Global Approval Hurdles

The development of ivonescimab, a bispecific antibody targeting PD-1 and VEGF, has positioned Akeso Inc. and Summit Therapeutics at the center of a high-stakes race in non-small cell lung cancer (NSCLC) treatment. While Phase III trials have demonstrated statistically significant improvements in progression-free survival (PFS) compared to established therapies like pembrolizumab and tislelizumab, the drug’s path to global approval remains fraught with regulatory and financial uncertainties. Investors must weigh the clinical promise of ivonescimab against the risks of unmet endpoints, competitive pressures, and the precarious financial health of Summit Therapeutics.

Clinical Promise and Safety Profile

Ivonescimab’s dual mechanism—simultaneously inhibiting PD-1 and blocking VEGF—has shown compelling results in late-stage trials. In the HARMONi-2 trial, the drug improved PFS by 49% compared to pembrolizumab in PD-L1-positive advanced NSCLC, with a hazard ratio (HR) of 0.51 (p < 0.00001) [1]. Similarly, the HARMONi-6 trial demonstrated a 52% reduction in disease progression risk versus tislelizumab plus chemotherapy (HR 0.52) [2]. These outcomes, presented at the 2025 World Conference on Lung Cancer, underscore ivonescimab’s potential to disrupt the NSCLC treatment landscape.

However, safety concerns persist. In the HARMONi trial, 56.9% of patients receiving ivonescimab plus chemotherapy experienced grade 3 or higher adverse events, compared to 50.0% in the chemotherapy-only group [3]. While the rate of fatal adverse events (1.8% vs. 2.8%) suggests manageable risks, the higher incidence of treatment-related side effects could limit adoption, particularly in markets prioritizing safety over incremental efficacy gains.

Regulatory Hurdles and Market Access

Despite its clinical strengths, ivonescimab faces significant regulatory barriers. The U.S. Food and Drug Administration (FDA) has not yet approved the drug, citing the lack of statistically significant overall survival (OS) improvements in the global HARMONi trial [4]. This shortcoming contrasts with its approval in China in May 2024, where it was granted first-line NSCLC indication based on PFS data from HARMONi-2 and HARMONi-6 [5]. The divergence in regulatory outcomes highlights the challenges of translating regional success into global market access.

The European Medicines Agency (EMA) and FDA are likely to demand additional OS data or biomarker-driven subgroup analyses before granting approval. For Akeso and Summit, this means prolonged development timelines and higher capital expenditures. Meanwhile, inclusion in China’s National Reimbursement Drug List (NRDL) has boosted commercial sales, but the company’s global ambitions hinge on navigating U.S. and European regulatory frameworks [6].

Financial Risks and Competitive Pressures

Summit Therapeutics, which holds the U.S. rights to ivonescimab, reported a net loss of $565.71 million in Q2 2025, with cash reserves of $297.9 million as of June 30, 2025 [7]. The company’s cash runway is projected to last less than a year, raising concerns about its ability to fund ongoing trials or secure partnerships. While Akeso’s parent company has stronger financials and reported record commercial sales in 2025, its reliance on ivonescimab for growth exposes it to similar risks if the drug fails to gain U.S. or European approval.

The competitive landscape further complicates the outlook. AstraZeneca’s rilvegostomig and Genmab’s acasunlimab are among the bispecific antibodies in Phase III trials for NSCLC, with the latter combining PD-L1 inhibition with 4-1BB activation [8]. The PD-1/VEGF bispecific market is projected to grow significantly, but ivonescimab’s differentiation will depend on its ability to demonstrate superior OS or unique biomarker responses.

Investment Implications

For investors, ivonescimab represents a high-reward, high-risk proposition. The drug’s approval in China and robust PFS data provide a near-term catalyst for Akeso’s revenue growth, particularly as it expands its global Phase III trials. However, the absence of OS improvements in key trials and Summit’s financial fragility pose existential threats. A strategic partnership or FDA breakthrough designation could alleviate some pressures, but the current trajectory suggests a binary outcome: either regulatory validation leading to blockbuster sales or a collapse in valuation if trials fall short.

In the short term, Akeso’s stock may benefit from its Chinese market dominance and NRDL inclusion, while Summit’s shares remain vulnerable to cash flow constraints. Long-term investors should monitor the HARMONi-OS follow-up data and the FDA’s stance on PFS as a surrogate endpoint. For now, the path to global approval for ivonescimab remains as uncertain as the financial futures of its developers.

Source:
[1] Zhen Su/LinkedIn, [Zhen Su: Phase III NSCLC results are out – Ivonescimab vs ...], [https://oncodaily.com/blog/140583]
[2] Akeso's 2025 Interim Results: Commercial Sales Reach New All-Time Highs, [https://www.prnewswire.com/news-releases/akesos-2025-interim-results-commercial-sales-reach-new-all-time-highs-302539063.html]
[3] Ivonescimab Plus Chemotherapy Demonstrates ..., [https://www.smmttx.com/pressrelease/https-www-smmttx-com-wp-content-uploads-2025-05-2025_pr_0530--harmoni-data--final-docx-pdf/]
[4] SMMT Q2 Loss Wider Than Expected, Ivonescimab Studies Focus, [https://www.nasdaq.com/articles/smmt-q2-loss-wider-expected-ivonescimab-studies-focus]
[5] Ivonescimab Data From Global Phase III HARMONi Study To Be Showcased At Presidential Symposium At WCLC 2025, [https://www.barchart.com/story/news/34144157/ivonescimab-data-from-global-phase-iii-harmoni-study-to-be-showcased-at-presidential-symposium-at-wclc-2025]
[6] 8 Bispecific Antibodies for NSCLC to Keep an Eye On, [https://www.delveinsight.com/blog/bispecific-antibodies-for-nsclc]
[7] Summit Therapeutics Reports Financial Results and Operational Progress for the Second Quarter Ended June 30, 2025, [https://www.smmttx.com/pressrelease/https-www-smmttx-com-wp-content-uploads-2025-08-2025_pr_0811--q2-2025-earnings-press-release--final-pdf/]
[8] PD-1 Non-Small Cell Lung Cancer Treatment Market, [https://www.credenceresearch.com/report/pd-1-non-small-cell-lung-cancer-treatment-market]