The designation of an orphan drug is typically granted to medications that meet specific criteria and treat rare, life-threatening, or chronically debilitating diseases. This designation offers several advantages to Sage, including Protocol Assistance or scientific advice that is tailored specifically to orphan drugs, the possibility of a centralized authorization procedure in Europe if the drug is successful in development and a marketing authorization application is submitted, and, if approved, a decade of market exclusivity and protection from other medications with the same indication being approved.
FDA Grants Fast Track Status to Biohaven’s Taldefgrobep Alfa to Treat Spinal Muscular Atrophy
Biohaven declared that it received Fast Track designation from the U.S. Food and Drug Administration for taldefgrobep alfa, a novel anti-myostatin adnectin, for the treatment of spinal muscular atrophy. Fast Track designation enables essential new drugs to reach patients earlier by facilitating more frequent communications with the F.D.A. and expeditious review of a drug that treats a serious condition and fills an unmet medical need. Biohaven previously received orphan drug designation from the F.D.A. for taldefgrobep in treating spinal muscular atrophy.
Spinal muscular atrophy is a rare motor neuron disease that progressively impairs muscle function and results in muscle atrophy, reduced motor function, and decreased quality of life, often leading to death. The disease hinders the growth and development of muscle mass, leading to weakness and debilitation. Inhibition of myostatin, a protein that restricts skeletal muscle growth, may be a promising therapeutic approach for spinal muscular atrophy as it promotes healthy muscular development, an essential process that is limited in this disease.
Taldefgrobep has the potential to be a novel therapy to be used in combination with disease-modifying therapies to enhance muscle function by blocking myostatin activity. Taldefgrobep’s novelty in myostatin inhibitors is based on its mechanism of action. It binds to myostatin to lower myostatin levels and functions as a receptor antagonist, thereby blocking myostatin signaling in skeletal muscles.
Biohaven, a pioneer in pioneering clinical trials for neurodegenerative conditions, is currently enrolling participants for a Phase III clinical trial investigating the effectiveness and safety of taldefgrobep alfa in individuals with spinal muscular atrophy. The trial, titled “A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants with Spinal Muscular Atrophy,” is a testament to Biohaven’s commitment to innovative research in the field of neurodegenerative diseases.
SpringWorks Therapeutics Announces FDA Acceptance and Priority Review of New Drug Application for Nirogacestat for Desmoid Tumors Treatment
On February 27, 2023, SpringWorks Therapeutics, Inc. announced today that the U.S. Food and Drug Administration (FDA) had accepted the Company’s New Drug Application (NDA) for nirogacestat, an investigational gamma-secretase inhibitor for the treatment of adults with Desmoid Tumors. The NDA was granted Priority Review and has been given a Prescription Drug User Fee Act (PDUFA) action date of August 27, 2023.
The NDA is being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program and is based on the previously announced positive results from the Phase 3 DeFi trial. DeFi (NCT03785964) is a global, randomized (1:1), double-blind, placebo-controlled Phase 3 trial evaluating the efficacy, safety, and tolerability of nirogacestat in adult patients with progressing Desmoid Tumors. DeFi includes an open-label extension phase, which is ongoing. Nirogacestat is an oral, selective, small-molecule gamma-secretase inhibitor in Phase 3 clinical development for Desmoid Tumors and in Phase 2 clinical development for ovarian granulosa cell tumors. Nirogacestat is an investigational drug for which safety and efficacy have not been established.
Moreover, nirogacestat has received Orphan Drug designation from the US FDA for the treatment of Desmoid Tumors and from the European Commission for the treatment of soft tissue sarcoma. The FDA also granted Fast Track and Breakthrough Therapy designations for treating adult patients with progressive, unresectable, recurrent, or refractory Desmoid Tumors or deep fibromatosis.
On achieving the milestone, Saqib Islam, Chief Executive Officer of SpringWorks, said, “the acceptance of our NDA for nirogacestat with Priority Review represents a significant milestone in our ambition to provide the first approved therapy for patients with Desmoid Tumors. We look forward to working closely with the FDA during the review process and remain focused on ensuring that we are well-positioned to expeditiously serve the desmoid tumor patient and the physician communities following approval.”
Desmoid tumors are rare, aggressive, locally invasive, and potentially morbid tumors of the soft tissues. As per NORD, Desmoid Tumors constitute 0.03% of all tumors. The estimated incidence in the general population is 2-4 per million people annually. Desmoid tumors are observed to be more common in persons aged 10–40 years but can occur in other age groups. Desmoid Tumors can commonly occur in women after childbirth. The female: male gender ratio is 2:1. In children; the gender incidence is the same. Currently, there are no FDA-approved therapies for the treatment of Desmoid Tumors. However, several major pharma and biotech giants are actively working to find a better treatment option for patients with Desmoid Tumors. The approval and the launch of Nirogacestat raise high hope for an improved treatment scenario.
AskBio Receives European Orphan Drug Designation for AB-1003 for the Treatment of Limb-Girdle Muscular Dystrophy (LGMD)
On February 27, 2023, Asklepios BioPharmaceutical, Inc. (AskBio), announced today that the European Commission (EC) had granted orphan drug designation for AB-1003 (also known as LION-101)* for the treatment of Limb-Girdle Muscular Dystrophy (LGMD). The EC decision, dated February 15, 2023, followed a positive opinion from the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) and was received through AskBio’s EU-based subsidiary BrainVectis.
AB-1003 is a novel investigational recombinant adeno-associated virus (AAV) based gene therapy currently being developed as a one-time intravenous (IV) infusion for the treatment of patients with LGMD type 2I/R9 (LGMD2I/R9). As per the latest updates, AB-1003 is being investigated in the US in a Phase 1/2 multicenter study that will evaluate the safety, tolerability, and efficacy of a single IV infusion of gene therapy in adult subjects with genotypically confirmed LGMD2I/R9.
Sheila Mikhail, Co-Founder & CEO, AskBio has expressed his opinion and said, “the EC orphan drug designation for AB-1003 is an important recognition of the unmet medical need in LGMD, which has no approved therapy. The burden of this rare form of muscular dystrophy on patients and their families is significant, and this decision supports our efforts to potentially bring a new therapeutic option to people in the EU living with the 2I/R9 type of this devastating disease.”
Limb-Girdle Muscular Dystrophy (LGMD) is a term for a group of diseases that cause progressive weakness and wasting of the muscles in the arms and legs. LGMD affects males and females in equal numbers. According to the NORD, the prevalence of Limb-Girdle Muscular Dystrophy is unknown, but estimates range from one in 14,500 to one in 123,000. The age of onset can vary greatly, even among individuals of the same family. The relative frequencies of the different types of Limb-Girdle Muscular Dystrophy vary from population to population, but worldwide LGMD2G, 2H and 2J are extremely rare. Limb-Girdle Muscular Dystrophy Type 2I/R9 (LGMD2I/R9) is a form of LGMD and is caused by mutations in the FKRP gene. Currently, there is no treatment that modifies the disease progression, and management is based on the signs and symptoms present in each individual. However, the emerging therapies like AB-1003 and other hold the potential to transform the treatment scenario.
Mitsubishi Tanabe Pharma America Announces 48-Week Results from Global, Open-Label, Phase 3 Trial of RADICAVA ORS® (edaravone) in ALS
On Feb. 27, 2023, Mitsubishi Tanabe Pharma America, Inc. (MTPA) announced the publication of results from the global, multi-center, open-label, Phase 3 clinical trial (MT-1186-A01) evaluating the long-term safety and tolerability of RADICAVA ORS® (edaravone) for the treatment of Amyotrophic Lateral Sclerosis (ALS) over 48 weeks of treatment. Results from the study, which was completed in March 2022, showed RADICAVA ORS was generally well tolerated during the treatment period, with no new safety signals identified. Study findings were published in Muscle & Nerve.
Study MT-1186-A01 enrolled 185 patients with Amyotrophic Lateral Sclerosis across 50 sites in the U.S., Canada, Europe, and Japan. No serious TEAEs related to the study drug were reported during the 48-week study period. Additionally, the discontinuation rate during the treatment period was 25%, with 8.6% of participants discontinuing the drug due to TEAEs. Finally, a total of 12 deaths were reported due to 13 TEAEs (respiratory failure, worsening of Amyotrophic Lateral Sclerosis, pneumonia, acute respiratory failure, lung disorder, diabetic ketoacidosis, feeding disorder, and suicide). None of the TEAEs leading to death were considered to be related to the study drug.
Gustavo A. Suarez Zambrano, M.D., Vice President of Medical Affairs at MTPA has said, “we’re encouraged by the data that we continue to collect from the global Phase 3 trial of RADICAVA ORS, demonstrating a favorable safety profile after 48 weeks of treatment. These data build upon the study’s 24-week findings that supported the FDA approval of RADICAVA ORS and underscore our commitment to growing our body of knowledge regarding the use of this treatment in people with ALS.”
Edaravone was discovered and developed for Amyotrophic Lateral Sclerosis by Mitsubishi Tanabe Pharma Corporation (MTPC) and Mitsubishi Tanabe Pharma Development America, Inc. (MTDA), commercialized in the U.S. by Mitsubishi Tanabe Pharma America, Inc. (MTPA). The U.S. Food and Drug Administration (FDA) approved RADICAVA® (edaravone) on May 5, 2017, and the oral formulation RADICAVA ORS® (edaravone) on May 12, 2022, for the treatment of Amyotrophic Lateral Sclerosis. RADICAVA is administered in 28-day cycles by IV infusion. It takes 60 minutes to receive each 60 mg dose. As per the further updates from Mitsubishi Tanabe Pharma America, to date, in the U.S., RADICAVA and RADICAVA ORS have been used to treat over 9,000 people with Amyotrophic Lateral Sclerosis, with over 1.2-million days of therapy and have been prescribed by nearly 2,000 HCPs.
