On December 19, 2022 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM, HKEX:​13) reported that it has initiated the filing of a rolling submission of a New Drug Application ("NDA") to the U.S. Food and Drug Administration ("FDA") for fruquintinib, a highly selective and potent oral inhibitor of VEGFR-1, -2 and -3, for the treatment of refractory metastatic colorectal cancer ("CRC") (Press release, Hutchison China MediTech, DEC 19, 2022, View Source [SID1234625403]). HUTCHMED plans to complete the NDA submission in the first half of 2023, to be followed by filing of a Marketing Authorization Application ("MAA") to the European Medicines Agency ("EMA") and an NDA to the Japan Pharmaceuticals and Medical Devices Agency ("PMDA").

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The U.S. FDA granted Fast Track Designation for the development of fruquintinib for the treatment of patients with metastatic CRC in June 2020, enabling the company to submit sections of the NDA on a rolling basis. The NDA is supported by the global Phase III multi-regional clinical trial (MRCT) FRESCO-2 study conducted in the U.S., Europe, Japan and Australia that investigated fruquintinib plus best supportive care ("BSC") vs placebo plus BSC in patients with refractory metastatic CRC.

The FRESCO-2 results were recently presented at the European Society for Medical Oncology Congress 2022. The study demonstrated that treatment with fruquintinib resulted in a statistically significant and clinically meaningful increase in the primary endpoint of overall survival ("OS") and the key secondary endpoint of progression free survival ("PFS") compared to treatment with placebo. Specifically, the median OS was 7.4 months for the 461 patients treated with fruquintinib compared to 4.8 months for the 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 for patients treated with fruquintinib compared to 1.8 months for patients 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% for patients in the placebo group. The safety profile of fruquintinib in FRESCO-2 was consistent with previously reported fruquintinib studies. Treatment related adverse events leading to discontinuation occurred in 20.4% of patients who received fruquintinib, compared to 21.1% of patients who received placebo.

"We are dedicated to executing on the next strategic steps in bringing fruquintinib to patients outside of China," said Dr. Weiguo Su, Executive Director, Chief Executive Officer and Chief Scientific Officer of HUTCHMED. "Colorectal cancer is one of the most common cancers worldwide, and over 50,000 people in the U.S. are estimated to die of colorectal cancer each year. Our U.S. NDA submission includes the successful multi-regional clinical trial, FRESCO-2, designed in consultation with the FDA, the EMA and the PMDA. The study showed a meaningful survival benefit and anti-tumor effect in patients treated with fruquintinib across patient populations, consistent with the pivotal Phase III FRESCO study supporting approval of fruquintinib for CRC in China. We look forward to submitting additional new drug applications in Europe and Japan next year."

Fruquintinib is approved in China under the brand name ELUNATE for the treatment of patients with metastatic CRC who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). It has been included in the China National Reimbursement Drug List ("NRDL") since January 2020. Approval in China is supported by the results of the FRESCO study, a Phase III pivotal trial of fruquintinib in 416 patients with metastatic CRC in China.

HUTCHMED retains all commercial rights to fruquintinib outside of China. In China, ELUNATE is partnered with Eli Lilly and Company.

About CRC

CRC is a cancer that starts in either the colon or rectum. CRC is the third most common cancer worldwide, estimated to have caused more than 915,000 deaths in 2020.1 In the U.S., an estimated 151,000 people will have been diagnosed with CRC and 53,000 people will have died from CRC in 2022.2 In Europe, CRC is the second most common cancer, with an estimated 507,000 new cases and 240,000 deaths in 2020.1 In Japan, CRC 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 inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.

About Fruquintinib Approval in China

CRC in China: Fruquintinib was approved for marketing by the China National Medical Products Administration ("NMPA") in September 2018 and commercially launched in China in November 2018 under the brand name ELUNATE. It has been included in the NRDL since January 2020. ELUNATE is indicated for the treatment of patients with metastatic CRC who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study3, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (NCT02314819).

About Other Fruquintinib Developments

The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated.

Gastric Cancer in China: The FRUTIGA study is a randomized, double-blind, Phase III study in China to evaluate fruquintinib combined with paclitaxel compared with paclitaxel monotherapy, for second-line treatment of advanced gastric cancer or GEJ adenocarcinoma (NCT03223376). Topline results were reported in November 2022. The trial met one of the primary endpoints of statistically significant improvement in PFS, which is clinically meaningful. The other primary endpoint of OS was not statistically significant per the pre-specified statistical plan, although there was a numerical improvement in median OS. Fruquintinib also demonstrated a statistically significant improvement in secondary endpoints including objective response rate (ORR), DCR, and improved duration of response (DoR). The safety profile of fruquintinib in FRUTIGA was consistent with previously reported studies. Full detailed results are subject to ongoing analysis and are expected to be disclosed at an upcoming scientific meeting. These results as well as further analyses will be shared with the China NMPA.

HUTCHMED is also developing fruquintinib for the treatment of multiple solid tumor cancers in combination with immunotherapies. Fruquintinib is being evaluated in combination with PD-1 monoclonal antibodies including tislelizumab (developed by BeiGene, Ltd) and sintilimab (developed by Innovent Biologics, Inc.) for the treatment of metastatic breast, endometrial and CRC in the U.S. (NCT04577963); gastric, CRC and NSCLC in China and Korea (initiated by BeiGene) (NCT04716634); and endometrial and other solid tumors in China (NCT03903705).

On December 19, 2022, F-star Therapeutics, Inc., a Delaware corporation (the "Company"), invoX Pharma Limited, a private limited company organized under the laws of England and Wales ("Parent") and Fennec Acquisition Incorporated, a Delaware corporation and a wholly owned subsidiary of Parent ("Purchaser" and together with the Company and Parent, the "Parties"), entered into Amendment No. 2 ("Amendment No. 2") to the Agreement and Plan of Merger, dated as of June 22, 2022, by and among the Parties and Sino Biopharmaceutical Limited, a company organized under the laws of the Cayman Islands, as "Guarantor" (the "Merger Agreement") (Filing, 8-K, F-star, DEC 19, 2022, View Source [SID1234625400]). Capitalized terms used herein without definition shall have the same meanings as assigned to them in the Merger Agreement or Amendment No. 2, as the case may be.

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Amendment No. 2 extends the End Date of the Merger Agreement from December 19, 2022 at 5:00 p.m., Eastern Time, to December 30, 2022 at one (1) minute past 11:59 p.m., Eastern Time. The parties are in discussions with the Committee on Foreign Investment in the United States (CFIUS) regarding the Transactions and have extended the End Date to provide for additional time to satisfy the Foreign Investment Condition with respect to CFIUS.

CFIUS has identified national security risks arising from the Transactions and is continuing to consider whether mitigation measures could adequately resolve the identified risks. On December 15, 2022, CFIUS advised the parties that it is availing itself of another 45-day investigation period, and that its investigation will be completed by no later than January 30, 2022, unless extended further.

Previously, the regulatory body in the United Kingdom, where the Company is based, cleared the voluntary notice filing regarding the Transactions under UK’s foreign investment regulations.

As previously described, the Merger Agreement may be terminated by either party, subject to certain exceptions, if any of the Offer conditions, are not satisfied or waived, to the extent waiveable, by Purchaser on or before the End Date.

Other than as expressly modified pursuant to Amendment No. 2, the Merger Agreement, which was previously filed as Exhibit 2.1 to the Current Report on Form 8-K filed with the Securities and Exchange Commission by the Company on June 23, 2022, remains in full force and effect as originally executed on June 22, 2022, as amended. The foregoing description of Amendment No. 2 does not purport to be complete and is subject to, and qualified in its entirety by, the full text of Amendment No. 2 attached hereto as Exhibit 2.1 to this Current Report on Form 8-K, which is incorporated herein by reference.

On December 19, 2022 EORTC and ALLIANCE reported that the target accrual in A031102/EORTC1407 TIGER study has been reached (Press release, EORTC, DEC 19, 2022, View Source [SID1234625398]).

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A031102/EORTC 1407 (TIGER) is an international phase III trial that seeks to establish the standard of care for second-line (also called initial salvage) chemotherapy in patients with advanced germ cell tumors (GCT). TIGER compares initial salvage conventional-dose chemotherapy (CDCT) with the TIP regimen vs. high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) with the TI-CE regimen with a primary endpoint of overall survival. The completion of patient recruitment is a major milestone for this groundbreaking trial.

EORTC would like to thank the collaborating groups who have supported this trial, including our funding partner @MOVEMBER. Without them, this trial would not have been possible in Europe.

"The TIGER trial is significant because collaboration between the Alliance/NCI and EORTC demonstrates that it is possible to conduct investigator-initiated randomized clinical trials in rare malignancies through the cooperative group mechanism in the absence of pharmaceutical company support. To our knowledge, TIGER is the first transatlantic cooperative group-led randomized trial conducted in GCT. This landmark study was open at 63 enters within 13 countries across 3 continents (North America, Europe, and Australia/New Zealand), and has helped pave the way for additional CTEP/NCI-led trials in other rare malignancies via collaboration with EORTC or other international partners."

On December 19, 2022 Eagle Pharmaceuticals, Inc. (Nasdaq: EGRX) ("Eagle" or the "Company") reported that the U.S. Food and Drug Administration ("FDA") has approved an additional indication for PEMFEXY (pemetrexed injection) in combination with pembrolizumab and platinum chemotherapy for the initial treatment of patients with metastatic, non-squamous, non-small cell lung cancer ("NSCLC") with no EGFR or ALK genomic tumor aberrations (Press release, Eagle Pharmaceuticals, DEC 19, 2022, View Source [SID1234625397]). Eagle’s approved PEMFEXY (pemetrexed injection) is a ready-to-dilute ("RTD") novel liquid intravenous formulation developed to eliminate the reconstitution step of the Listed Drug ("LD"), ALIMTA.

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"With this fifth indication, PEMFEXY is now approved for all of the same indications as ALIMTA, and we believe it allows for key advantages such as eliminating the need for reconstitution. Since its initial launch in February 2022, PEMFEXY has been an important addition to Eagle’s hospital and acute care product portfolio, and we are pleased to bring this treatment option to patients undergoing chemotherapy. At the same time, we also believe that Eagle is well positioned to capture the commercial opportunity that PEMFEXY represents," stated Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals.

Effective October 1, 2022, the Company amended its agreement to reduce future royalties related to PEMFEXY profits from 25% to a range of 0% to 12.5% based on aggregate profits achieved in exchange for a one-time payment of $15 million.

In February 2020, Eagle received approval from the FDA of its New Drug Application for PEMFEXY, following the settlement agreement of patent litigation with Eli Lilly and Company (NYSE: LLY) in December 2019. The agreement provided for a release of all claims by the parties and allowed for an initial entry of PEMFEXY into the market (equivalent to approximately a three-week supply of current ALIMTA utilization) on February 1, 2022, and a subsequent uncapped entry on April 1, 2022.

On December 19, 2022 Carrick Therapeutics, an oncology-focused biopharmaceutical company discovering and developing highly differentiated therapies, and the Menarini Group ("Menarini"), a privately-held, leading international pharmaceutical company, reported a clinical trial collaboration and supply agreement (Press release, Carrick Therapeutics, DEC 19, 2022, https://www.carricktherapeutics.com/carrick-therapeutics-menarini-group-announce-clinical-trial-collaboration-evaluate-samuraciclib-elacestrant-combination/ [SID1234625396]).

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This agreement covers the execution of a Phase 2 clinical trial to evaluate the novel combination of Carrick’s samuraciclib (CT7001), an oral and first-in-class inhibitor of CDK7, and Menarini‘s oral selective estrogen receptor degrader (SERD), elacestrant, in patients with CDK4/6i resistant HR+, HER2- metastatic breast cancer. Menarini and Carrick will jointly sponsor the clinical trial.

"We are excited to initiate this collaboration with Menarini to explore the potential of samuraciclib in combination with elacestrant for the treatment of advanced breast cancer," said Tim Pearson, Chief Executive Officer of Carrick Therapeutics. "Our pre-clinical work and prior clinical studies have validated the biology for SERD combinations with CDK7, pointing to potential synergies when combining samuraciclib with Menarini’s oral SERD, elacestrant. This collaboration represents a shared commitment to maximizing the potential of novel combination therapies to improve outcomes for people living with breast cancer."

"This new clinical collaboration with Carrick Therapeutics is yet another step we are making to develop elacestrant in an extensive way to address unmet needs of patients resistant to CDK4/6 therapies in HR+, HER2- metastatic breast cancer," said Elcin Barker Ergun, Chief Executive Officer of Menarini. "Menarini will continue to pursue research collaborations that have the potential to improve patients’ lives in breast cancer."

Carrick anticipates initiating the Phase 2 clinical trial in 2023. This new study will expand Carrick’s portfolio of ongoing clinical trials with samuraciclib. The company presented encouraging results from a clinical study combining samuraciclib with fulvestrant at the 2021 San Antonio Breast Cancer Symposium.