FDA Approvals in 2024: Novel Therapies for MASH, WHIM Syndrome, Pediatric Glioma, MDS, and Bladder Cancer
核心洞察
The FDA approved Madrigal's Rezdiffra, the first treatment for metabolic dysfunction-associated steatohepatitis (MASH (搜索)), addressing a significant unmet need in liver disease.
X4 Pharmaceuticals' Xolremdi (搜索) gained approval as the first targeted therapy for WHIM syndrome (搜索), a rare immunodeficiency, marking a milestone for the company.
Day One Biopharmaceuticals' Ojemda secured approval for BRAF (搜索)-altered pediatric low-grade glioma (搜索), offering a new treatment option for this common childhood brain tumor.
The FDA has issued over 130 approvals this year, with more than 40 being for novel drugs. Several companies, including Madrigal Pharmaceuticals, X4 Pharmaceuticals, Day One Biopharmaceuticals, Geron Corporation, and ImmunityBio, have recently celebrated their first FDA approvals for therapies addressing conditions with high unmet needs. These approvals span a range of diseases, including metabolic dysfunction-associated steatohepatitis (MASH (搜索)), WHIM syndrome (搜索), pediatric low-grade glioma (搜索), myelodysplastic syndromes (MDS (搜索)), and non-muscle invasive bladder cancer (搜索) (NMIBC).
Madrigal Pharmaceuticals: Rezdiffra for MASH
Madrigal Pharmaceuticals' Rezdiffra (resmetirom) gained FDA approval as the first treatment for MASH (搜索), a type of fatty liver disease affecting 5.3 out of every 1,000 people worldwide. Rezdiffra is indicated for patients with moderate to advanced liver fibrosis, alongside diet and exercise. The approval was based on the Phase III MAESTRO-NASH trial, where Rezdiffra met its primary endpoints, demonstrating significant improvement in disease resolution and liver fibrosis. Specifically, MASH resolved in 25.9% of patients receiving 80 mg and 29.9% of patients receiving 100 mg of Rezdiffra, with no worsening of fibrosis. Rezdiffra targets thyroid hormone receptor beta (THR-β (搜索)), which plays a crucial role in maintaining liver homeostasis.
X4 Pharmaceuticals: Xolremdi for WHIM Syndrome
X4 Pharmaceuticals received approval for Xolremdi (搜索) (mavorixafor) as the first targeted treatment for WHIM syndrome (搜索), an ultra-rare immunodeficiency affecting fewer than 1,000 people in the U.S. Xolremdi, an oral CXCR4 (搜索) antagonist, is designed to mobilize white blood cells from the bone marrow into the blood to improve immune deficiencies. Phase III 4WHIM trial results showed a 60% reduction in annualized infection rate compared to placebo; treated participants had less than one infection per year compared with 4.5 for the placebo group.
Day One Biopharmaceuticals: Ojemda for Pediatric Low-Grade Glioma
Day One Biopharmaceuticals secured approval for Ojemda (tovorafenib) in BRAF (搜索)-altered pediatric low-grade glioma (搜索) (pLGG), the most common form of childhood brain tumor. Ojemda's accelerated approval was based on overall response rate in patients with complete response, partial response or minor response. Ojemda is the first FDA-approved medicine for children with BRAF fusions or rearrangements, which are the most common molecular alteration in pLGG.
Geron Corporation: Rytelo for Myelodysplastic Syndromes
Geron Corporation's Rytelo (imetelstat) received FDA approval for lower- to intermediate-risk myelodysplastic syndromes (MDS (搜索)). Rytelo is a telomerase (搜索) inhibitor. The approval was based on the Phase III IMerge trial, in which Rytelo had significantly higher rates of red blood cell transfusion independence (RBC-TI) over placebo for at least 24 weeks (28% vs 3%). In responders, RBC-TI was sustained for a median of 1.5 years.
ImmunityBio: Anktiva for Non-Muscle Invasive Bladder Cancer
ImmunityBio's Anktiva (nogapendekin alfa inbakicept) was approved for non-muscle invasive bladder cancer (搜索) (NMIBC) in BCG-unresponsive patients with carcinoma in situ. Anktiva is a therapeutic fusion protein that combines a mutant version of the IL-15 (搜索) cytokine with an IL-15 receptor fusion protein. In the Phase II/III QUILT-3.032 study, maintenance treatment with Anktiva and BCG for up to 18 months led to a complete response rate of 62%, with duration of response exceeding 47 months at the November 2023 cut-off.