SMMT Stock Plummets 25% on Regional Data Differences in NSCLC Study

Shares of Summit Therapeutics SMMT tanked 25% yesterday after it reported a final analysis of data from the HARMONi study, which evaluated its investigational antibody ivonescimab in certain patients with non-small cell lung cancer (NSCLC).

This analysis showed a wide difference in the progression-free survival (PFS) benefit between Asian and Western patients.

More on SMMT’s HARMONi Study Results

The HARMONi study enrolled patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who had progressed after treatment with an EGFR-TKI. The study assessed two primary endpoints — PFS and overall survival (OS).

Earlier in May, Summit reported the primary analysis of data from the HARMONi study, which showed a statistically significant benefit in the PFS endpoint — treatment with the drug plus chemotherapy cut the risk of disease progression by 48% compared with chemotherapy alone. However, the final analysis revealed regional variation. In Asian patients, the drug combination cut the risk of disease progression by 45%, compared with 33% in Western patients.

Concerning the OS endpoint, Summit had previously reported that the study only showed a positive trend; although the combination therapy reduced the risk of death by 21%, the results were not statistically significant. However, the final analysis showed a slightly more favorable trend toward the Western patients, as the median OS in North American patients has yet to be reached.

Summit is developing ivonescimab in collaboration with China-based Akeso. The company acquired an exclusive license from Akeso in 2022 to develop and market the drug in the United States, Canada, Europe and Japan. Akeso retains the rights to market the drug in China, where it is currently approved to treat two distinct NSCLC indications.

SMMT Share Price Performance

Summit’s stock fell as investors were likely disappointed with the wider-than-expected PFS gap between the Western and Asian patient sub-groups. The wide difference also raises questions about whether data from Asian patients is truly comparable to that in the West.

Investors were also disappointed by the lack of a clear OS benefit, given that the FDA has previously indicated OS would be required to support marketing authorization for ivonescimab in the United States.

Year to date, the stock has gained 9% compared with the industry’s 12% growth.

Recent Developments With SMMT’s Ivonescimab

Summit Therapeutics came into the investor spotlight last year after reporting encouraging results from the HARMONi-2 study, which evaluated ivonescimab against Merck’s MRK blockbuster PD-1 inhibitor Keytruda in patients with locally advanced or metastatic NSCLC whose tumors had positive PD-L1 expression. Treatment with the drug cut the risk of disease progression or death by nearly half compared with Keytruda.

In April, SMMT reported positive results from the Akeso-sponsored phase III HARMONi-6 study, which evaluated ivonescimab plus chemotherapy against BeiGene’s PD-1 inhibitor Tevimbra plus chemotherapy in patients with locally advanced or metastatic squamous NSCLC, regardless of PD-L1 expression. The study met its primary endpoint of PFS — patients treated with the ivonescimab regimen showed statistically significant and clinically meaningful improvement over those who received the Tevimbra combination regimen.

Based on the above results, we believe that ivonescimab could replace PD-(L)1 inhibitors as the next standard of care across multiple NSCLC settings. Unlike Keytruda/Tevimbra, which targets the PD-1 protein, the Summit drug is a first-in-class bispecific antibody that targets two proteins, namely PD-1 and VEGF. We believe that this dual mechanism differentiates ivonescimab from currently available therapies for solid tumors, as there is a potentially higher expression of both these proteins in tumor tissue compared with the normal tissues in the body.

Apart from HARMONi, Summit is conducting two more late-stage studies on the drug in separate NSCLC settings. Both studies are currently enrolling patients.

Therapies Rivaling SMMT’s Ivonescimab

Developing bispecific antibodies that target two proteins, namely PD-1 and VEGF, has lately been one of the lucrative areas in cancer treatment. Companies like BioNTech BNTX/Bristol Myers BMY, Pfizer and Merck are also developing their respective PD-1/VEGF-targeting antibody candidates.

Earlier this year, Bristol Myers signed a similar licensing deal worth $11 billion with BioNTech. Per the deal terms, Bristol Myers and BioNTech will jointly develop and market BNT327, an investigational bispecific antibody targeting PD-L1 and VEGF, along with profits on an equal basis.

In May, Pfizer entered into a multi-billion-dollar deal with Chinese biotech 3SBio for the latter’s PD-1/VEGF bispecific antibody SSGJ-707.

Last year, Merck signed a deal with China-based LaNova Medicines for the latter’s LM-299, which is also based on the same mechanism as ivonescimab. Merck intends to advance the drug's clinical development “with speed and rigor for patients in need.”

Despite the competition, we believe that Summit enjoys the advantage of being ahead in clinical development over the BioNTech/Bristol Myers, Merck and Pfizer therapies. These candidates are still at least a year away from reaching the same clinical development position as SMMT.

Summit Therapeutics PLC Price

 

Summit Therapeutics PLC price | Summit Therapeutics PLC Quote

SMMT’s Zacks Rank

Summit currently carries a Zacks Rank #4 (Sell).

You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here.

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