8-K: Summit Therapeutics Partner Akeso Receives Approval in China for Ivonescimab Second Indication, Shows Positive Overall Survival Trend

Summit Therapeutics announces its partner Akeso received approval from Chinese authorities for a second indication of ivonescimab and reported positive overall survival trends in a Phase III trial.

Summary

• Summit Therapeutics' partner, Akeso, has received approval from the Chinese National Medical Products Administration (NMPA) for a second indication of ivonescimab.
• The approval is based on results from the Phase III HARMONi-2 clinical trial (AK112-303).
• HARMONi-2 evaluated ivonescimab monotherapy against pembrolizumab monotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with positive PD-L1 expression.
• Akeso also disclosed an interim overall survival analysis with a hazard ratio of 0.777 at 39% data maturity, suggesting a potential 22% reduction in the risk of death compared to pembrolizumab.
• Summit Therapeutics is currently enrolling patients in the HARMONi-7 study, a multiregional Phase III trial evaluating ivonescimab monotherapy against pembrolizumab monotherapy in patients with locally advanced or metastatic NSCLC with positive PD-L1 expression.
• Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multi-regional Phase III clinical trials, HARMONi and HARMONi-3, and the Company has begun to activate clinical trial sites in the United States for HARMONi-7.
• Enrollment in HARMONi was completed in the second half of 2024, and top-line results are expected to be announced in the middle of this year.

Sentiment

Score: 7

Explanation: The sentiment is positive due to the approval in China and promising interim survival data, but tempered by the fact that it's an interim analysis and the drug is still investigational in major markets.

Positives

• Ivonescimab receives approval for a second indication in China, expanding its market potential.
• The interim overall survival analysis shows a positive trend, suggesting a potential benefit for patients.
• Ivonescimab demonstrated a statistically significant improvement in progression-free survival (PFS) in the HARMONi-2 trial.
• Summit is actively progressing the clinical development of ivonescimab with ongoing Phase III trials.
• The Fast Track designation from the FDA could expedite the approval process in the United States.
• Akeso announced that the results of this interim overall survival analysis included a clinically meaningful hazard ratio of 0.777.

Negatives

• The overall survival data is from an interim analysis at 39% data maturity, so the final results could differ.
• HARMONi-2 is a single-region study conducted in China, which may limit the generalizability of the results.
• Ivonescimab is still an investigational therapy in Summit's licensed territories and is not approved in the US or Europe.
• The analysis was conducted at 39% data maturity, with a nominal alpha level of 0.0001.

Risks

• The success of ivonescimab depends on the outcomes of ongoing and future clinical trials.
• Regulatory approvals in the US and Europe are not guaranteed.
• Competition from other therapies in the NSCLC market could impact ivonescimab's commercial potential.
• The Company's ability to sell shares of our common stock under the ATM Program, the conditions affecting the capital markets, general economic, industry, or political conditions, the results of our evaluation of the underlying data in connection with the development and commercialization activities for ivonescimab, the outcome of discussions with regulatory authorities, including the Food and Drug Administration, the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials, the results of such trials, and their success, global public health crises, that may affect timing and status of our clinical trials and operations, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials or preclinical studies will be indicative of the results of later clinical trials, whether business development opportunities to expand the Company's pipeline of drug candidates, including without limitation, through potential acquisitions of, and/or collaborations with, other entities occur, expectations for regulatory approvals, laws and regulations affecting government contracts and funding awards, availability of funding sufficient for the Company's foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the 'Risk Factors' section of filings that the Company makes with the Securities and Exchange Commission.

Future Outlook

Summit expects top-line results from the HARMONi trial in the middle of this year and is continuing to enroll patients in the HARMONi-7 trial. The company is focused on the clinical development of ivonescimab in NSCLC.

Management Comments

• 'We are pleased to see that a trial that was designed to test for progression-free survival as the sole primary endpoint demonstrates a clinically meaningful overall survival trend at just 39% data maturity,' added Robert W. Duggan, Chairman and Co-Chief Executive Officer and Dr. Maky Zanganeh, Co-Chief Executive Officer and President of Summit.
• The clinically meaningful overall survival trend underscores the opportunity of ivonescimab to represent a potential to be the next generation in PD-1 directed immunotherapy, and potentially make a significant difference in the lives of patients with lung cancer and prospectively other tumors.

Industry Context

This announcement highlights the growing importance of bispecific antibodies in cancer immunotherapy. Ivonescimab's dual mechanism of action (PD-1 and VEGF blockade) positions it as a potential competitor to existing PD-1 inhibitors like pembrolizumab and other anti-angiogenic therapies in the NSCLC market.

Comparison to Industry Standards

• Pembrolizumab (Keytruda) is a leading PD-1 inhibitor used as a monotherapy or in combination for NSCLC, setting a high benchmark for efficacy and safety.
• The reported hazard ratio of 0.777 for overall survival with ivonescimab suggests a potentially competitive profile compared to pembrolizumab in PD-L1 positive NSCLC.
• Atezolizumab (Tecentriq) is another PD-L1 inhibitor commonly used in NSCLC, and ivonescimab's results will likely be compared against its efficacy data.
• Other bispecific antibodies targeting different pathways are also being developed for NSCLC, creating a competitive landscape for novel immunotherapies.

Stakeholder Impact

• Shareholders may react positively to the news of approval and positive clinical data.
• Patients with NSCLC in China gain access to a new treatment option.
• Employees of Summit and Akeso are involved in the development and commercialization of ivonescimab.
• The results could impact the competitive landscape for suppliers of cancer therapies.

Next Steps

• Summit will continue enrolling patients in the HARMONi-7 trial.
• Top-line results from the HARMONi trial are expected in the middle of this year.
• Summit will continue clinical development of ivonescimab in NSCLC.
• Akeso will continue to market ivonescimab in China for its approved indications.

Key Dates

Keywords

ivonescimab, Summit Therapeutics, Akeso, NSCLC, lung cancer, PD-L1, HARMONi-2, clinical trial, NMPA, approval, oncology, pembrolizumab