Hutchison Pharmaceutical: Fruquintinib submitted a rolling marketing application to the FDA

Hehuang Medical Guanwei announced on December 19 that its company has begun to submit a rolling new drug application for fruquintinib for the treatment of refractory metastatic colorectal cancer to the US Food and Drug Administration (FDA). 。 Fruquintinib is a highly selective and potent oral vascular endothelial growth factor receptor ("VEGFR")-1, -2, and -3 inhibitor. Hutchison plans to complete the NDA submission in the first half of 2023, followed by a MAA application to the European Medicines Agency ("EMA") and a new drug application to the Japan Agency for Pharmaceuticals and Medical Devices ("PMDA").

– The Company plans to complete the rolling filing of new drug applications in the United States in the first half of 2023, followed by European and Japanese filings –

– Global Phase III FRESCO-2 Study in the United States, Europe, Japan and Australia Supports the New Drug Application –

– FRESCO-2 Study Shows Fruquintinib Treatment Reduces the Risk of Death in Metastatic Colorectal Cancer by 34% (0.66 HR) –

In June 2020, the US FDA granted fruquintinib fast-track designation for the treatment of patients with metastatic colorectal cancer, allowing Hutchison to submit new drug applications in batches in a rolling submission. The FRESCO-2 study, a global phase III international multicenter clinical trial (MRCT) of fruquintinib plus best supportive care versus placebo plus best supportive care in patients with refractory metastatic colorectal cancer, supported the new drug application.

The results of the FRESCO-2 study were presented at the recent European Society for Medical Oncology (ESMO) Annual Meeting 2022. This study showed that fruquintinib achieved statistically significant and clinically significant lengths in both overall survival ("OS") and progression-free survival ("PFS") for the key secondary endpoint compared to placebo. Specifically, the median OS of 461 patients treated with fruquintinib was 7.4 months, compared with 4.8 months for 230 patients in the placebo group (hazard ratio ["HR"] 0.66; 95% confidence interval ["CI"] 0.55–0.80; p<0.001). The median PFS was 3.7 months in patients treated with fruquintinib compared with 1.8 months in the placebo group (HR 0.32; 95% CI 0.27–0.39; p<0.001）。 The disease control rate ("DCR") was 55.5% in the fruquintinib group compared to 16.1% in the placebo group. The safety profile of fruquintinib in FRESCO-2 studies is consistent with what was observed in previous studies. In 20.4% of patients receiving fruquintinib, treatment-related adverse events leading to discontinuation of the drug were experienced, compared with 21.1% in the placebo group.

IN CHINA, FRUQUINTINIB IS MARKETED UNDER THE TRADE NAME ® ELUNATE® FOR THE TREATMENT OF PATIENTS WITH METASTATIC COLORECTAL CANCER WHO HAVE PREVIOUSLY RECEIVED FLUOROPYRIMIDINE, OXALIPLATIN, AND IRINOTECAN, INCLUDING THOSE WHO HAVE PREVIOUSLY RECEIVED ANTI-VEGF THERAPY AND/OR ANTI-EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) THERAPY (RAS WILD TYPE). It has been included in China's national medical insurance drug list since January 2020. The approval of fruquintinib in China is based on the successful results of the FRESCO study. The FRESCO study is a pivotal phase III registration study of fruquintinib, which included a total of 416 colorectal cancer patients in China.

Hutchison Pharma owns all commercialization rights to fruquintinib outside of China. In China, Hutchison Pharma cooperated with Eli Lilly to promote Ayotek ®.

About colorectal cancer

Colorectal cancer, a cancer that begins in the colon or rectum, is the third most common cancer in the world, causing an estimated more than 915,000 deaths in 2020. [1] In the United States, an estimated 151,000 new cases of colorectal cancer and 53,000 deaths will occur in 2022. [2] In Europe, colorectal cancer is the second most common cancer, with an estimated 507,000 new cases and 240,000 deaths in 2020. [1] In Japan, colorectal cancer is the most common cancer, with an estimated 147,000 new cases and 59,000 deaths in 2020. [1]

About fruquintinib

Fruquintinib is a highly selective and potent oral VEGFR-1, -2, and -3 inhibitor. VEGFR inhibitors play a crucial role in inhibiting angiogenesis in tumors. The unique design of fruquintinib makes its kinase more selective for lower off-target toxicity, higher tolerance, and more stable coverage of the target. To date, fruquintinib has been generally well tolerated in patients and has demonstrated a low potential for drug-drug interactions in preclinical studies, or makes it well suited for use in combination with other cancer therapies.

About fruquintinib approved in China

Research on metastatic colorectal cancer in China: Fruquintinib was approved for sale in China by the National Medical Products Administration of China ("NMPA") in September 2018 and commercially launched under the trade name Ayote ® in November 2018. It has been included in China's national medical insurance drug list since January 2020. Ayote ® is indicated for patients with metastatic colorectal cancer who have previously received fluoropyrimidine, oxaliplatin and irinotecan, including patients who have previously received anti-VEGF therapy and/or anti-epidermal growth factor receptor (EGFR) therapy (RAS wild type). The results of the fruquintinib FRESCO pivotal phase III registration study [3] in 416 patients with metastatic colorectal cancer in China were published in the Journal of the American Medical Association (JAMA) in June 2018 (NCT02314819).

Other development projects regarding fruquintinib

The safety and efficacy of fruquintinib for the following research uses is not clear, and there is no guarantee that it will be approved by health authorities or commercially available for research use in any country or region.

Chinese Gastric Cancer Study: The FRUTIGA study is a randomized, double-blind phase III clinical trial to evaluate the efficacy and safety of fruquintinib and paclitaxel combination therapy in patients with advanced gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma that does not respond to first-line standard chemotherapy (NCT03223376). The top-line results of the FRUTIGA study were published in November 2022. The study met one of the primary endpoints, a statistically significant improvement in PFS, which is clinically significant. The other primary endpoint, OS, although improvements were observed on median OS, were not statistically significant according to the preset statistical plan. In addition, fruquintinib observed statistically significant improvements in secondary endpoints including objective response rate (ORR), DCR, and prolonged duration of response (DoR). The safety profile of fruquintinib in FRUTIGA studies is also consistent with those observed in previous studies. The full detailed results of the study are subject to further analysis and are expected to be presented at an upcoming academic conference. These results and further analysis will be submitted to the NMPA.

Hutchison is also developing fruquintinib combined immunotherapy for the treatment of various solid tumors. Currently, studies have been initiated to evaluate fruquintinib in combination therapy with PD-1 monoclonal antibodies, including tislelizumab (developed by BeiGene) and sintilimab (developed by Innovent Biopharma (Suzhou) Co., Ltd.). Studies include the US study of metastatic breast, endometrium, and colorectal cancer (NCT04577963) initiated in the United States, and the gastric, colorectal and non-small cell lung cancer (initiated by BeiGene) study initiated in China and South Korea (NCT04716634); and endometrial cancer and other solid tumors initiated in China (NCT03903705).