HLB "FDA Strongly Recommends Reexamination Application for 'Riboceranib'"

HLB recently announced on the 3rd that it received a Complete Response Letter (CRL) regarding the combination therapy of the anticancer drug Lenvatinib and Camrelizumab, and that the U.S. Food and Drug Administration (FDA) strongly recommended submitting a resubmission application.

Jinyangon, Chairman of HLB, announced through the company's YouTube channel last June that they received a Complete Response Letter (CRL) regarding the FDA approval application for the anticancer new drug, Rivoceranib. [Image source=HLB YouTube]

HLB’s anticancer drug Lenvatinib aimed for FDA approval through combination therapy with Camrelizumab, an immuno-oncology drug developed by China’s Hansoh Pharmaceutical. However, on May 16 (local time), when the FDA was scheduled to decide on the approval, the FDA issued a CRL. A CRL is a letter issued by the FDA when additional data supplementation or on-site inspections are required for a new drug application. To obtain approval, the identified issues must be corrected and supplemented before reapplying for approval.

The issues pointed out involved facility-related matters discovered during the Chemistry, Manufacturing, and Controls (CMC) inspection process of Hansoh Pharmaceutical, the manufacturer of Camrelizumab, the drug used in the combination therapy. The CRL also reportedly included that the Bioresearch Monitoring Program (BIMO) inspection, which involves direct FDA inspection of clinical trial sites and medical institutions, was not conducted.

However, on the 2nd (local time), HLB explained that most of these concerns were resolved following a meeting between HLB’s U.S. subsidiary Elevate Therapeutics, Hansoh Pharmaceutical, and the FDA. HLB stated, “The FDA strongly recommended submitting a resubmission application to resume the review,” and that it received an official document (PAL) related to this.

Regarding the issues raised after the CMC on-site inspection, HLB explained, “Hansoh Pharmaceutical had already submitted thorough supplementary materials on these matters before receiving the CRL,” and “the FDA confirmed that sufficient explanations were provided and conveyed that no additional supplementary documents were requested.” In other words, Hansoh Pharmaceutical does not need to prepare separate experiments or documents; it only needs to resubmit the Biologics License Application (BLA) reflecting the supplementary materials already submitted to the FDA.

However, since the resubmission review period is set to a maximum of two months (Class 1) or six months (Class 2), and the approval decision will be made within that period, if designated as Class 1, approval within the year is possible, but if designated as Class 2, approval within the year is expected to be difficult.

During this resubmission process, HLB plans to submit additional data demonstrating the efficacy of the combination therapy to further enhance the efficacy of Lenvatinib and obtain approval. They plan to submit the final clinical data from the global Phase 3 clinical trial (CARES-310) disclosed at last month’s American Society of Clinical Oncology (ASCO). Initially, the median overall survival (mOS) of the combination therapy was announced as 22.1 months at the 2022 European Society for Medical Oncology (ESMO), breaking the 20-month barrier that previous treatments had never surpassed. However, the final mOS of the combination therapy was extended to 23.8 months. HLB explained, “The mOS was extended as a result of analyzing patients who additionally participated in the late stage of the clinical trial.”

HLB also emphasized that regarding the BIMO inspection, the FDA confirmed that “the BIMO issue was not a major reason for issuing the CRL.” Although the BIMO inspection of clinical trial institutions in Russia and Ukraine, which are currently at war, was considered a factor in issuing the CRL due to practical difficulties, this point was clearly distinguished. HLB stated, “If documents are submitted, the FDA will conduct the BIMO inspection during the resubmission review period.”

With the uncertainty removed following this meeting, HLB plans to focus on the remaining procedures for global approval. Hanyanghae, CTO of HLB Group, said, “Since Hansoh Pharmaceutical’s confidence that sufficient supplementary documents have already been submitted regarding the FDA’s points was confirmed as true, we plan to perfectly prepare and submit the resubmission application as soon as possible,” adding, “Although there has been some delay compared to the plan, this opportunity allowed a thorough inspection of the manufacturing plant, enhancing external trust in product quality, and enabling the official reflection of superior new drug data, which is expected to have positive effects in the future.”