HUTCHMED (China) Limited ("HUTCHMED" or the "Company") (Nasdaq/AIM:HCM; HKEX:13) announced that the U.S. Food and Drug Administration ("FDA" or the "Agency") has issued a Complete Response Letter ("CRL") regarding the New Drug Application ("NDA") for surufatinib for the treatment of pancreatic ("pNETs") and extra-pancreatic (non-pancreatic, "epNETs") neuroendocrine tumors ("NETs"). FDA determined that the current data package, based on two positive Phase III trials in China and one bridging study in the United States (U.S.), does not support an approval in the U.S. at this time. The CRL indicated that a multi-regional clinical trial ("MRCT") is required for U.S. approval.
The safety and efficacy of surufatinib, an oral inhibitor of angiogenesis and immune modulation, was demonstrated in the SANET-p and SANET-ep studies, two randomized double-blind Phase III trials in patients with advanced pNETs and epNETs conducted in China. Results of a HUTCHMED sponsored bridging study conducted in the U.S. suggest similar safety and efficacy to the SANET study population in China. Surufatinib was approved in China for the treatment of pNETs and epNETs in June 2021 and December 2020, respectively.
Surufatinib received U.S. FDA Fast Track Designations in April 2020 for the treatment of pNETs and epNETs. Orphan Drug Designation for pNETs was granted in November 2019. In a May 2020 pre-NDA meeting, HUTCHMED reached an agreement with the FDA that the two positive Phase III studies of surufatinib in patients with pNETs and epNETs in China, along with the bridging trial in the U.S. could form the basis to support a U.S. NDA submission. The FDA accepted the filing of the NDA on June 30, 2021.
The FDA evaluated the applicability of the SANET studies data generated in one country to U.S. patients and U.S. medical practice. The CRL stated that the FDA will require a MRCT that includes subjects more representative of the US patient population and aligned to current U.S. medical practice. In addition, pandemic-related issues concerning inspection scheduling and access contributed to the FDA action. This action by the FDA is not related to any safety issues with surufatinib. HUTCHMED is working with the FDA to evaluate next steps.
Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, commented: "Although this decision from the FDA is disappointing, we remain confident about the clinical value of surufatinib for NET patients and committed to making surufatinib available to patients globally. We look forward to working with the Agency to evaluate its feedback. Throughout the duration of the U.S. review process, we have been transparent and collaborative with the FDA. There are very few treatments approved and used in these rare diseases, and patients and physicians would benefit from more options to address the unmet medical need. We look forward to continued engagement with the FDA on developing a plan to bring surufatinib to patients in the U.S."
HUTCHMED International, headquartered in Florham Park, New Jersey, drives clinical and regulatory development in the US, Europe and Japan. Dr Marek Kania, Executive Vice President, Managing Director and Chief Medical Officer of HUTCHMED International, commented: "Our global development strategy remains unchanged. Outside of the U.S. and China, we remain committed to engaging with regulators in Europe, where our Marketing Authorization Application ("MAA") submission for surufatinib is under review, and in Japan where we have an ongoing Japanese bridging study. Furthermore, our foundational approach is to conduct multi-regional registration trials, such as our 14-country, 691-patient FRESCO-2 Phase III trial for fruquintinib for patients with metastatic colorectal cancer which is expected to read-out in the second half of this year."