Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Elevar Therapeutics announced its plans to resubmit its application to the FDA for rivoceranib in combination with camrelizumab as a first-line treatment for unresectable hepatocellular carcinoma (uHCC). The follows a Type A meeting with the FDA on July 2, 2024, where the agency confirmed that the resubmission can proceed without delay and that additional GMP and Bioresearch Monitoring (BIMO) inspections may occur post-resubmission. The original NDA, submitted in May 2023, was met with a complete response letter citing GMP deficiencies at China-based partner Jiangsu Hengrui Pharma's facility and incomplete BIMO clinical inspections due to FDA travel restrictions. There were no issues related to clinical data or the rivoceranib manufacturing site. Elevar intends to resubmit the NDA promptly, including data from the CARES-310 study, which showed a median overall survival of 23.8 months for patients with uHCC.

FDA confirmed resubmission can occur without delayFDA confirmed additional GMP and/or BIMO inspections may occur after resubmissionElevar plans to resubmit as soon as possible FORT LEE, N.J., July 09, 2024 (GLOBE NEWSWIRE) -- Elevar Therapeutics, Inc. (Elevar), a majority-owned subsidiary of HLB Co., Ltd., today announced near-term plans for resubmission of the NDA for rivoceranib in combination with camrelizumab as a first-line treatment option for Unresectable Hepatocellular Carcinoma (uHCC) after a Type A meeting with the FDA on July 2. The meeting was requested by Jiangsu Hengrui Pharmaceuticals (Hengrui Pharma) to address items cited in the May 16 FDA Complete Response Letters (CRLs) sent to Hengrui Pharma and Elevar. The original NDA was submitted by Elevar in May 2023. The CRL cited GMP deficiencies at the Hengrui Pharma facility where camrelizumab is manufactured and incomplete Bioresearch Monitoring (BIMO) clinical inspections due to FDA travel restrictions. The FDA did not indicate any issues related to clinical data or with the manufacturing site for rivoceranib. Prior to the Type A meeting, the FDA had accepted Hengrui Pharma’s written responses to GMP deficiencies. During the meeting, the FDA confirmed resubmission can occur without delay. The FDA also confirmed BIMO inspections due to FDA travel restrictions may occur after resubmission. “The most critical outcome from our discussion with the FDA is that resubmission of Elevar’s NDA can occur without further remediation at the Hengrui manufacturing site,” commented Dr. Saeho Chong, Elevar chief executive officer. “Elevar left the meeting very motivated and with a clear path forward for resubmission, so patients and providers can soon have access to this novel combination therapy for uHCC where there continues to be a high unmet need. The resubmission will include the CARES-310 landmark analysis recently presented at ASCO, demonstrating the longest median overall survival (mOS of 23.8 months) for any treatment in a global Phase 3 trial for patients with uHCC.” About Hepatocellular Carcinoma (HCC) HCC is the most common type of primary liver cancer. It most frequently develops in people with chronic underlying liver inflammation which may be from viral and non-viral causes. HCC typically has a poor prognosis with limited treatment options and continues to be a diagnosis with an ongoing urgent medical need. About CARES-310CARES-310 (NCT03764293) was a randomized, open-label, international Phase 3 study, which included 543 patients with unresectable or metastatic HCC who had not received prior systemic therapy. Patients were randomized 1:1 to receive the combination of camrelizumab + rivoceranib or sorafenib (400 mg orally twice daily), a standard-of-care first-line multi-kinase inhibitor treatment for uHCC. Camrelizumab was administered intravenously (190 mg) every two weeks and rivoceranib was administered orally (250 mg) once daily. The study was conducted at 95 study sites across 13 countries/regions, in which systemic treatment for uHCC independent of etiology, rivoceranib plus camrelizumab demonstrated statistically significant and clinically meaningful prolonged overall survival and progression-free survival and improved overall response rate versus sorafenib. The co-primary endpoints were overall survival and progression-free survival. Secondary endpoints included objective response rate and duration of response. About Camrelizumab Camrelizumab (SHR-1210) is a humanized monoclonal antibody that binds to the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Camrelizumab is developed by Hengrui Pharma and has been studied in more than 5,000 patients. Currently, 50 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer, etc.) and treatment settings. Camrelizumab, under the brand name AiRuiKa®, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), in combination with rivoceranib as a treatment for uHCC (first-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma and nasopharyngeal carcinoma in the first-line setting. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021. In October 2023, Elevar licensed camrelizumab, an anti-PD-1 antibody, for commercialization from Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma) worldwide excluding Greater China and Korea. About Rivoceranib Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), is a highly potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway for tumor angiogenesis. VEGFR-2 inhibition is a clinically validated approach to limit tumor growth and disease progression. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf®). Rivoceranib was the first TKI approved in gastric cancer in China (November 2014). It is also approved in China in combination with camrelizumab as a first-line treatment for uHCC (January 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in uHCC (U.S.). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese -territory license-holder, Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), under the brand name Aitan®. About Elevar TherapeuticsElevar Therapeutics, Inc. is a fully integrated biopharmaceutical company built on the promise of elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options. With expertise rooted in oncology, Elevar is focused on identifying and developing promising medicines for complex yet under-treated health conditions. Elevar’s lead proprietary drug candidate is rivoceranib. Elevar is headquartered in New Jersey, with offices in South Korea. Additional information is available at ElevarTherapeutics.com. Media Contact: Jeanette BressiHead, Corporate Communications, Elevar Therapeuticsjbressi@elevartherapeutics.com609-439-3997 Investor Contact:Wade SmithChief Financial Officer, Elevar Therapeutics wsmith@elevartherapeutics.com

Merck licenced xevinapant from Debiopharm International in 2021 in a deal worth $1.08bn. Image Credit: Anne Czichos / Shutterstock Merck KGaA (Merck) has discontinued the Phase III TrilynX trial evaluating xevinapant in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). The company stated that its decision was informed by a pre-planned interim analysis performed by the Independent Data Monitoring Committee. It found that the study is “unlikely to meet its primary objective of prolonging event-free survival”. Merck licenced xevinapant from Debiopharm International in a deal worth $1.08bn in 2021. Xevinapant is an inhibitor of apoptosis protein (IAP) antagonist designed to restore cancer cell sensitivity to apoptosis. Following the news of trial termination, Merck’s stock was down by over 10% in trading on the Frankfurt Stock Exchange. The randomised placebo-controlled Phase III TrilynX trial (NCT04459715) enrolled approximately 730 participants with LA SCCHN. The study evaluated xevinapant in combination with chemoradiation therapy versus placebo and chemoradiation. The trial’s primary endpoint was event-free survival for up to five years. See Also: AstraZeneca’s Tagrisso receives approval in Japan for lung cancer AstraZeneca’s Truqap and Faslodex combo receives approval in EU Merck was quick to add that the safety data for xevinapant was “overall compatible with the chemo-radio sensitizing properties of the therapy”. The company plans to conduct an in-depth review of the data and share these results in the future. Xevinapant was touted as Merck’s big oncology therapy, per its 2023 annual statement. The company prioritised its importance, especially after its multiple sclerosis therapy, evobrutinib, failed to meet primary endpoints in Phase II trials . Other therapies in the company’s oncology portfolio are HRS-1167, a selective poly (ADP-ribose) polymerase 1 (PARP1) trapping inhibitor, and a Claudin-18.2 antibody-drug conjugate (ADC) SHR-A1904. Merck licenced the therapies from Chinese company Jiangsu Hengrui Pharmaceuticals in a deal worth up to $1.48bn, in October 2023. In April, Merck invested over €300m ($320.8m) in a new Life Science Research Center at its global headquarters in Darmstadt, Germany. The centre, which is expected to open in 2027, will be responsible for developing biopharmaceuticals, including antibodies and messenger ribonucleic acid applications.