Here is information on the latest US FDA approvals, the week of February 12 – February 16, 2024
Amtagvi for Melanoma
The FDA has granted accelerated approval of lifileucel (Amtagvi) for adult patients with unresectable metastatic melanoma previously treated with a PD-1 inhibitor and, if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. Lifileucel, a tumor-derived autologous T cell immunotherapy, is the first FDA-approved T cell therapy for a solid tumor cancer. It is manufactured using a proprietary process that collects and expands a patient’s T cells from a portion of their tumor, which are then infused back into the patient. Melanoma, an aggressive skin cancer often linked to ultraviolet light exposure, accounts for about 1% of skin cancers but a significant number of skin cancer deaths due to its potential to metastasize if not caught and treated early. The FDA’s decision was based on outcomes from a global, multicenter, multicohort clinical study including adults with unresectable or metastatic melanoma previously treated with systemic therapies. Lifileucel demonstrated a 31.5% objective response rate among 73 evaluated patients, including both complete and partial responses. Importantly, a significant proportion of responders maintained their response at 6, 9, and 12 months without disease progression or death. The phase 3 TILVANCE-301 trial is underway to confirm clinical benefit. The FDA granted the approval of lifileucel to Iovance Biotherapeutics Inc.
Iloprost Injection for Frostbite
The FDA has approved iloprost (Aurlumyn) injection for treating severe frostbite in adults to reduce the risk of finger or toe amputation. This marks the first-ever FDA-approved treatment option for severe frostbite. Iloprost is a vasodilator that opens blood vessels and prevents blood clotting, offering a new tool for physicians to help prevent the life-changing amputation of frostbitten fingers or toes. Frostbite occurs in various stages, with severe frostbite involving frozen skin and underlying tissue, potentially leading to stopped blood flow and necessitating amputation. Iloprost’s effectiveness in severe frostbite was primarily demonstrated in an open-label, controlled trial that included 47 adults with severe frostbite. Iloprost was previously approved in 2004 for treating pulmonary arterial hypertension. The approval of iloprost was granted to Eicos Sciences Inc.
MDMA-Assisted Therapy for PTSD
The FDA has accepted a new drug application from Lykos Therapeutics, previously known as MAPS Public Benefit Corporation, for MDMA-assisted therapy in treating post-traumatic stress disorder (PTSD). This therapy, combining MDMA use with psychotherapy, could become the first of its kind to receive federal approval, introducing a novel treatment avenue for individuals suffering from severe mental health conditions. PTSD affects approximately 13 million Americans each year with women and disadvantaged or marginalized groups more likely to be affected. Lykos Therapeutics’ application is supported by the results of two Phase 3 clinical trials, MAPP1 and MAPP2, which demonstrated the treatment’s efficacy and safety in patients with severe PTSD, noting no serious adverse events among those receiving MDMA. Standard treatment for PTSD is trauma-focused talk therapy alone or in combination with the SSRIs sertraline or paroxetine. According to a manufacturer press release, “while there have been advancements in the management of PTSD, there have been no new drug treatments approved by the FDA in over twenty years.” The PDUFA target action date is August 11, 2024.
NALIRIFOX for Pancreatic Cancer
The FDA has approved NALIRIFOX as a first-line treatment for patients with metastatic pancreatic cancer. This is the first approval of a first-line treatment for pancreatic cancer in over ten years. NALIRIFOX is a combination chemotherapy regimen consisting of liposomal irinotecan (Onivyde®), 5-fluorouracil (5-FU)/leucovorin, and oxaliplatin. It is intended for patients who have not received previous treatment for metastatic pancreatic cancer. Liposomal irinotecan, part of this combination, is already approved for use in combination with 5-FU/leucovorin for patients with metastatic pancreatic cancer treated with gemcitabine. The FDA’s approval was based on the positive survival benefit shown in the phase 3 NAPOLI 3 clinical trial, in which NALIRIFOX demonstrated an overall survival of 11.1 months compared to 9.2 months for the current standard-of-care treatment of gemcitabine plus nab-paclitaxel. NALIRIFOX differs from FOLFIRINOX, another combination chemotherapy for metastatic pancreatic cancer, by including liposomal irinotecan instead of irinotecan. Liposomal irinotecan is designed for longer retention in the body before breakdown, which may contribute to the efficacy and safety profile of NALIRIFOX. The approval was granted to Ipsen, the manufacturer of one of the key components of NALIRIFOX.
Tepotinib for NSCLC
The FDA has approved tepotinib (Tepmetko) for the treatment of patients with non-small cell lung cancer (NSCLC) with mesenchymal-epithelial transition (MET) exon 14 skipping alterations. This follows an accelerated approval granted in February 2021. Tepotinib targets and inhibits the MET gene alteration, present in about 2-3% of patients with NSCLC. The full approval of tepotinib was based on the results from the VISION phase 2 trial. In treatment-naive patients, the overall response rate (ORR) was 57%, with 40% of responders having a duration of response (DOR) of 12 months or longer. Among previously treated patients, the ORR was 45%, with 36% having a DOR of 12 months or longer. The median overall survival (OS) was 20 months. The approval of tepotinib for NSCLC with MET was granted to EMD Serono.
https://pubmed.ncbi.nlm.nih.gov/37270698/
Omalizumab for Food Allergies
The FDA has approved omalizumab (Xolair) injection to reduce the severity of allergic reactions to one or more foods, making it the first FDA-approved medication to treat allergic reactions to multiple foods from accidental exposure. Specifically, the indication is for IgE-mediated food allergy in adult and pediatric patients aged 1 year and older for the reduction of allergic reactions (Type I), including anaphylaxis, that may occur with accidental exposure to one or more foods. To be used in conjunction with food allergen avoidance. The approval came two months after the FDA accepted the companies’ supplemental biologics license application for this indication. Nearly 17 million people in the U.S. have IgE-mediated food allergies, with more than 40% of them being children, according to a manufacturer press release. The approval is based on the results of a phase 3 OUtMATCH trial, which showed that omalizumab significantly increased the amount of peanut, milk, egg and cashew, it took to cause an allergic reaction compared to placebo. Omalizumab was initially approved in the US in 2003 and also carries indications for the treatment of asthma, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria. The approval was granted to Roche and Novartis. https://www.gene.com/download/pdf/xolair_prescribing.pdf
Budesonide Oral Suspension for EOE
The FDA has approved budesonide oral suspension (Eohilia) for the treatment of eosinophilic esophagitis (EoE) in individuals 11 years of age and older. Budesonide oral suspension is the only FDA-approved oral therapy specifically for this patient population. EoE is characterized as a chronic, immune-mediated disease that inflames the esophagus, leading to symptoms that can significantly impact quality of life, including painful swallowing and potential food impaction. The precise cause of EoE is not fully understood but is believed to be linked to various food and environmental allergens. If not properly managed, EoE can lead to complications such as esophageal narrowing. According to a manufacturer press release, the new formulation of budesonide, a corticosteroid available in several forms, has been developed to possess thixotropic properties, allowing it to flow more freely when shaken and return to a more viscous state upon swallowing. This feature helps ensure consistent dose delivery directly to the esophagus, where it can effectively address the inflammatory condition and symptoms associated with EoE, such as difficulty swallowing and choking. The approval is based on the results from two studies, each 12 weeks long, demonstrating efficacy in achieving histologic remission and significantly improving patient-reported dysphagia symptoms. According to the prescribing information budesonide oral suspension has not been shown to be safe and effective for the treatment of EoE for longer than 12 weeks. The approval was granted to Takeda.
https://www.takeda.com/newsroom/newsreleases/2024/fda-approves-eohilia/
https://content.takeda.com/?contenttype=PI&product=EOH&language=ENG&country=USA&documentnumber=1
TriClip® for tricuspid regurgitation
The FDA has approved the TriClip™ Transcatheter Edge-to-Edge Repair (TEER) system manufactured by Abbott for the treatment of tricuspid regurgitation (TR), a condition characterized by the leakage of the tricuspid valve, which can cause significant strain on the heart and lead to other cardiovascular issues. This approval marks the TriClip as a first-of-its-kind device, designed specifically to offer a minimally invasive treatment option for a condition that has historically had limited therapeutic interventions. The TriClip system addresses TR through a minimally invasive procedure that clips together parts of the valve’s leaflets to improve closure and blood flow direction, offering a significant improvement in quality of life for those who are not suitable candidates for surgery. The approval of TriClip was based on data from the TRILUMINATE pivotal trial, which demonstrated the safety, effectiveness, and quality-of-life benefits of the device. Notably, the trial reported that 90% of patients treated with the TriClip experienced marked improvement in the severity of their TR, with sustained improvement in their quality of life one-year post-procedure.
https://abbott.mediaroom.com/2024-02-13-FDA-Advisory-Committee-Votes-in-Favor-of-Abbotts-First-of-Its-Kind-TriClip-TM-System-to-Treat-People-With-a-Leaky-Tricuspid-Heart-Valve
ACE2016 for Solid Tumors
The FDA has cleared the investigational new drug (IND) application for ACE2016, an allogeneic gamma delta 2 (γδ2) T cell therapy for the treatment of solid tumors expressing the epidermal growth factor receptor (EGFR). The clearance will allow the initiation of a Phase 1, first-in-human trial to evaluate the safety, tolerability, and pharmacodynamics of ACE2016 in adults with locally advanced or metastatic EGFR-expressing solid tumors. The trial is expected to begin in the second half of 2024. ACE2016, being developed by Acepodia, uses a proprietary Antibody-Cell Conjugation (ACC) technology, which enables the conjugation of tumor-targeting antibodies to γδ2 T cells, enhancing their ability to target and kill EGFR-expressing cancer cells.
https://www.biospace.com/article/releases/acepodia-announces-fda-clearance-of-investigational-new-drug-application-for-ace2016-a-first-in-class-allogeneic-anti-egfr-cell-therapy/
Human Acellular Vessel (HAV) for Vascular Trauma
The FDA has granted Priority Review to Humacyte’s Biologics License Application (BLA) for the Human Acellular Vessel (HAV) for use in urgent arterial repair following extremity vascular trauma, specifically when synthetic graft options are not suitable and autologous vein use is not feasible. The HAV technology comprises a universally implantable, bioengineered human tissue that does not necessitate immune suppression and exhibits resistance to infection post-implantation. The BLA is backed by results from the V005 Phase 2/3 clinical trial and real-world evidence from its use in treating wartime injuries in Ukraine under a Humanitarian Aid Program. These findings demonstrated reduced rates of amputation and infection compared to traditional synthetic graft benchmarks. This expedited review process is scheduled to conclude by the PDUFA date of August 10, 2024.