Welcome to this week’s Regulatory Insights from Synopulse, featuring the latest updates from the FDA, EMA, and other global regulatory authorities. From groundbreaking drug approvals to critical recalls and new designations, we cover the most significant events driving the pharmaceutical sector. This comprehensive report offers a concise view of the regulatory milestones shaping the pharma, biotech, and MedTech industries, keeping you informed and ahead in a competitive landscape.
The United States Food and Drug Administration (FDA)
The past year drew to a close when the thumbs-up from Bristol Myers Squibb came for OPDIVO Qvantig (nivolumab + hyaluronidase-nvhy ). OPDIVO Qvantig becomes the first and only co-formulated PD-1 inhibitor with Halozyme’s ENHANZE drug delivery technology for subcutaneous administration. The United States Food and Drug Administration approved this following the multi-center, randomized, open-label CheckMate-67T trial. The time-averaged concentration over 28 days achieved a concentration of Cavgd28 with a GMR of 2.10 with a confidence interval of 90% being 2.00 to 2.20. Additionally, the GMR has also achieved a minimum concentration at a steady state of 1.77, with 90% of the confidence interval reaching from 1.63 to 1.93.
On December 30, Verastem Oncology disclosed that the US FDA has accepted the New Drug Application (NDA) for avutometinib combined with defactinib for the treatment of recurrent KRAS mutant low-grade serous ovarian cancer (LGSOC). The indicated combination therapy has received a priority review under the accelerated approval pathway with a PDUFA target action date of June 30, 2025. If approved, this would be the first treatment approved specifically by the FDA for recurrent KRAS mutant LGSOC. This NDA follows promising results from the Phase 2 RAMP 201 trial, which showed excellent efficacy with durable responses and tolerability profiles. Verastem is also enrolling patients for the RAMP 301 Phase 3 trial that potentially could broaden the indication irrespective of KRAS mutation status. The FDA’s Priority Review underscores the highly unmet need for these treatments in such a rare cancer. Verastem thus plans for commercial launch mid-2025.
Telix Pharmaceuticals announced on December 30 that it will be submitting the Biologics License Application (BLA) with the FDA for the use of TLX250-CDx (Zircaix®) as a PET imaging agent to diagnose kidney cancer. TLX250-CDx is an investigational product aimed to be used for non-invasive diagnosis and characterization of clear cell renal cell carcinoma (ccRCC) which is the most common and aggressive form of kidney cancer. If approved, this would be the first targeted PET agent for kidney cancer available commercially in the U.S. The FDA will then provide a PDUFA goal date after the administrative 60-day review of the submitted application.
On December 30, Precigen has completed the rolling submission of a Biologics License Application (BLA) to the United States Food and Drug Administration for PRGN-2012 (zopapogene imadenovec), an investigational AdenoVerse® gene therapy meant for treating recurrent respiratory papillomatosis in adults. The submission is currently undergoing the initial 60-day review during which, the FDA will decide whether to accept or reject the BLA for further review along with the deadline of the PDUFA action date. The Company requested a priority review, which would reduce the review timeline to 6 months. PRGN-2012 serves to elicit immune responses against HPV 6 or HPV 11-infected cells. If it receives approval, it would be the first FDA therapeutic approved for RRP, a rare and chronic disease with no current cures; patients of this disease usually undergo repeated surgeries. The BLA submission is supported by data from the primary endpoints in safety and efficacy demonstrated by complete responses in patients from the Phase 1/2 pivotal clinical study (NCT04724980). This is an important stride in the direction of a much-needed therapy for RRP patients—a disease that frequently entails considerable morbidity. FDA granted BTD in June 2023, ODD in March 2021 and Accelerated Approval in August 2023. EMA granted ODD in January 2024.
On December 30, NRx Pharmaceuticals announced the first section of the New Drug Application (NDA) for NRX-100 (ketamine) to the U.S. Food & Drug Administration (FDA). Awarded Fast Track Designation in 2017, NRX-100 is investigated for treatment of suicidal bipolar depression, in combination with NRX-101 (D-cycloserine/lurasidone.) The aim is to extend this new application towards Suicidal Ideation in Major Depressive Disorder and other forms of depression using NIH-and European Government-funded trial data. NRx must now submit the 1,800-page manufacturing section (Module 3) immediately for review by the FDA before final efficacy data and the other portions of the NDA, expected first quarter of 2025.
Kazia Therapeutics issued a regulatory update on paxalisib, which included details from the Type C meeting with the US FDA regarding the treatment for glioblastoma (GBM) on December 31. In July of 2024, Kazia released topline data from the GBM-AGILE study, where it was shown that paxalisib provided a clinically meaningful improvement in overall survival (OS) in patients with new diagnosis unmethylated (NDU) glioblastoma. Accordingly, Kazia reached out to the FDA for feedback regarding possible clinical and regulatory approaches based on the findings. FDA’s position seems to state that OS data is generally not appropriate for accelerated approval but could support traditional approval. The FDA also endorsed key aspects of a proposed Phase 3 registrational study, including the patient population, primary endpoint, and comparator arm. The company is still looking into other indications for paxalisib-namely pediatric brain cancer, brain metastases, and breast cancers with PI3K pathway mutations, which have exciting data presented in the meeting in San Antonio on Breast Cancer. Kazia intends to outline the next steps by January 2025 to maximize value for shareholders.
On January 1, MicuRx Pharmaceuticals, which is involved in drug discovery and development, has announced that it has been granted the Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for self-delivered anti-infective drug MRX-5, which now provides treatment for infections caused by NTMs (non-tuberculous).
China’s National Medical Products Administration (NMPA)
On January 3, Innovent Biologics received the second NDA in China for DOVBLERON® (taletrectinib adipate capsule), a next-generation ROS1 tyrosine kinase inhibitor (TKI), is approved by the National Medical Products Administration (NMPA), to treat adult patients suffering from locally advanced or metastatic ROS1-positive non-small-cell lung cancer (NSCLC). The approval comes after the positive outcome of the Phase 2 TRUST-I trial, which demonstrated very impressive, durable overall responses, with a confirmed objective response rate of 91% in ROS1 TKI-naïve patients and 88% intracranial cORR. Results of the trial at 2024 ASCO Annual Meeting and published in the Journal of Clinical Oncology also stated that it had not yet reached the median duration of response and progression-free survival after 23.5 months of follow-up. DOVBLERON®, already approved by the NMPA in December 2024, is for patients with ROS1-positive NSCLC having up to two ROS1 TKI treatments. This signifies the growth of the commercial portfolio in Innovent as well as strengthens its TKI franchise.
