FDA Grants Priority Review to NDA of Fruquintinib for Metastatic CRC

The FDA has granted priority review of the new drug application (NDA) for fruquintinib (HMPL-013) for the treatment of adult patients with previously treated metastatic colorectal cancer (CRC).¹

Fruquintinib is a highly selective and potent inhibitor of VEGFR -1, -2 and -3 that has been shown to inhibit the migration, proliferation, and survival of endothelial cells, and inhibit microvessel formation, tumor cell proliferation, and tumor cell death. This NDA is supported by results from the FRESCO-2 study (NCT04322539) which met its primary and secondary end points showing a significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS), respectively, and reduced the risk of death by 34% in patients with refractory mCRC, as well as data from the phase 3 FRESCO trial conducted in China.²

If granted approval, fruquintinib will be the first and only highly selective inhibitor of all 3 VEGF receptors to be approved in the United States for this patient population. Additionally, the FDA has set a Prescription Drug User Fee Act (PDUFA) goal date for the NDA of November 30, 2023.

“We are confident that fruquintinib has the potential to transform the treatment landscape for those living with previously treated metastatic colorectal cancer, as demonstrated by its strong clinical profile,” said Awny Farajallah, MD, head of Global Medical Affairs Oncology at Takeda, in the press release. “There are significant needs for patients with this disease in the [United States], and we believe fruquintinib has the potential to address these needs regardless of patients’ biomarker status. We look forward to continuing conversations with the FDA with the goal to make this therapy available to patients as soon as possible.”

In the randomized, double-blind, placebo-controlled, phase 3 FRESCO-2 study, 691 patients with refractory mCRC from the United States, Europe, Japan, and Australia were included if they had received prior chemotherapy, and anti-VEGF therapy.³ Patients who were RAS wild-type received prior anti-EGFR therapy, and those with BRAF V600E-mutant or microsatellite instability- high disease must have received ≥ 1 targeted regimen, as well as prior trifluridine/tipiracil (Lonsurf) and/or regorafenib (Stivarga) exposure.

Once enrolled, patients were given fruquintinib combined with best supportive care (BSC) or placebo and BSC. Oral fruquintinib was given to patients at a dose of 5 mg once daily, 3 weeks on and 1 week in 28-day cycles. Placebo was given using the same dosing schedule.

The primary end point of the study was OS and the secondary end points were PFS, objective response rate (ORR), disease control rate, and safety.

The median duration of treatment in the study was 11.3 months among patients given fruquintinib and 11.2 months for those given placebo. Data showed that the median OS with fruquintinib and BSC was 7.4 months compared with 4.8 months with placebo and BSC, showing a significant improvement (HR, 0.66; 95% CI, 0.55-0.80; P < .0001).² For the secondary end point of PFS, the median PFS in the fruquintinib and BSC arm was 3.7 months vs 1.8 months in the placebo and BSC arm (HR, 0.32; 95% CI, 0.27-0.39; P < .001), an ORR of 1.5% vs 0%, and DCR of 55.5% vs 16.1%, respectively.

For safety, 62.7% of patients in the fruquintinib arm experienced grade 3 or higher adverse events (AEs) vs 50.4% of those in the placebo arm. For those in the fruquintinib vs placebo arms, AEs that occurred in greater than 5% of patients were hypertension (13.6% vs 0.9%), asthenia (7.7% vs 3.9%), and hand-foot syndrome (6.4% vs 0%).

“The clinical benefit of fruquintinib has been confirmed in multiple ways, from global clinical studies to commercialization in China. We are pleased to have Takeda as our partner furthering development and commercialization of fruquintinib outside of China,” said Michael Shi, MD, head of research and development and chief medical officer, HUTCHMED, in the press release. “Today’s acceptance marks a significant advancement towards the goal of providing patients with previously treated metastatic colorectal cancer a much-needed therapeutic option, given the limited treatment options currently available to patients. This also supports our ongoing vision to design and develop differentiated molecules that help patients with high unmet needs globally.”

REFERENCES

1. Takeda and HUTCHMED announce new drug application (NDA) for fruquintinib for treatment of previously treated metastatic colorectal cancer granted priority review. News release. HUTCHMED. May 25, 2023. Accessed May 26, 2023. https://tinyurl.com/2ryxvzcv

2. Dasati NA, Lonardi S, Garcia-Carbonero R, et al. LBA25 - FRESCO-2: A global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Ann oncol. 2022;33 (suppl_7): S808-S869. doi:10.1016/annonc/annonc1089

3. A study of efficacy and safety of fruquintinib (HMPL-013) in patients with metastatic colorectal cancer (FRESCO-2). ClinicalTrials.gov. Updated March 29, 2023. Accessed May 26, 2023. https://clinicaltrials.gov/ct2/show/NCT04322539