Hutchmed and Eli Lilly Halt China Stomach Cancer Filing Due to Approval Doubts
Hutchmed has chosen to withdraw its application for the VEGFR inhibitor fruquinitib in combination with chemotherapy as a second-line treatment for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in China. The decision follows an internal review and discussions with Chinese regulatory authorities. The company, which co-markets the drug with Eli Lilly in China under the brand name Elunate, determined that approval is unlikely at this time. Consequently, Hutchmed plans to reassess its strategy moving forward.
The phase 3 FRUTIGA trial formed the basis for the submission. This trial was initially deemed positive as it met one of its dual primary endpoints. However, Chinese authorities raised concerns regarding Elunate’s performance on the other primary endpoint, overall survival. Specifically, the trial demonstrated that among patients who had progressed on first-line chemotherapy, Elunate plus paclitaxel reduced the risk of progression or death by 43% compared to paclitaxel alone. Patients receiving the combination treatment experienced a median progression-free survival of 5.6 months, versus 2.7 months for those in the control group.
Despite these promising results, Elunate showed only a slight 4% advantage in overall survival, which was not statistically significant. More troubling was the observation that starting around 18 months into the treatment, patients in the control group were more likely to be alive than those treated with Elunate. Based on these findings, Chinese drug reviewers and external committee members concluded that the survival results could not justify an approval.
In response to the outcome, Hutchmed's CEO and chief scientific officer, Weiguo Su, Ph.D., expressed disappointment but remained hopeful about the potential of fruquinitib in treating gastric cancer. Su emphasized that the data from the FRUTIGA trial suggests fruquinitib plus paclitaxel could become a promising new treatment option for certain patients in the future.
China represents a significant market for gastric cancer, accounting for about 40% of the world’s new diagnoses. However, the advent of PD-1 inhibitors combined with chemotherapy has established a new standard of care for the first-line treatment of some stomach cancer patients, potentially complicating the evaluation of second-line treatments like Elunate.
Meanwhile, in the United States, the FDA is scrutinizing the use of PD-1 drugs in first-line stomach cancer treatment. The agency has called for an advisory committee meeting to discuss whether certain medications should be limited based on the cancer’s PD-L1 expression levels. Currently, existing approvals for Bristol Myers Squibb’s Opdivo and Merck & Co.’s Keytruda in HER2-negative gastric and GEJ cancers apply to a broad patient population, irrespective of PD-L1 expression.
Beyond China, fruquinitib received FDA approval in November 2023 and European Commission approval in June 2024 as a monotherapy for previously treated colorectal cancer. Takeda, which holds ex-China rights for the drug, does not have any other phase 3 trials for fruquinitib listed in its pipeline.
In the first half of 2024, fruquinitib’s ex-China sales reached $130.5 million, while sales of Elunate in China, recorded by Lilly, were $61 million. Additionally, Hutchmed has partnered with Innovent Biologics on the PD-1 inhibitor Tyvyt, also tied to Lilly. An application for the combined use of Elunate and Tyvyt in endometrial cancer was accepted by Chinese authorities with a priority review in April, and a phase 3 trial for this combination in kidney cancer has been fully enrolled.
How to obtain the latest research advancements in the field of biopharmaceuticals?
In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!
