Here is information on the latest US FDA approvals, the week of September 25 – September 29, 2023
Ryzumvi (Phentolamine Ophthalmic Solution) for Dilated Pupils
The FDA has approved Ryzumvi (phentolamine ophthalmic solution) 0.75% for the treatment of pharmacologically-induced mydriasis (dilated pupils). Mydriasis results from adrenergic agonists, such as phenylephrine or parasympatholytic agents, such as tropicamide. The manufacturers, Viatris and Ocuphire Pharma, note in a written release that an estimated 100 million comprehensive eye exams take place each year and involve pharmacologically-induced mydriasis (or dilation) of the pupils. The effect can last up 24 hours and include sensitivity to light and blurred vision. Ryzumvi was evaluated in the comprehensive MIRA clinical trial program involving more than 600 subjects. Ryzumvi is a relatively non-selective alpha-1 and alpha-2 adrenergic agonist that reversibly binds to receptors on the iris dilator muscle, thereby reducing pupil diameter. The approval of Ryzumvi arrives following a New Drug Application (NDA) filing in December and acceptance of the NDA by the FDA in February. Ryzumvi, formerly called Nyxol is expected to be available in the US in the first half of 2024 and is currently the only commercially available treatment option indicated for the reversal of dilated eyes.
https://www.ryzumvi.com/files/prescribing-information.pdf
Exxua (Gepirone Hydrochloride) for MDD
The FDA has approved Exxua (extended-release gepirone hydrochloride tablets) for the treatment of major depressive disorder in adults. According to the manufacturer Fabre-Kramer, while the mechanism of the antidepressant effect is not completely understood, Exxua is the “first and only approved” antidepressant for the treatment of MDD in adults that works through the selective agonism of 5HT1a receptors. The company expects to launch Exxua in early 2024. Data in more than 5000 patients showed that the most common adverse events were dizziness and nausea, which were mostly mild and transient. Sexual side effects and weight gain, often associated with antidepressants, were not more common among Exxua-treated patients than among placebo comparators. Exxua has encountered regulatory setbacks along the way to this approval. The company filed the first New Drug Application for Exxua in September 1999 and it was subsequently rejected in 2002. In 2015, an advisory committee meeting voted 9-4 against an approval, due to a lack of evidence to support the drug’s efficacy, although there was an 11-2 vote supporting safety. The current prescribing information includes a boxed warning for increased risk of suicidal thinking and behavior in pediatric and young adult patients taking antidepressants, although again Exxua is indicated only for adults with MDD.
https://fabrekramer.com/exxua-for-generalized-anxiety-disorder/
https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021164s000lbl.pdf
Likmez, Liquid Formulation of Metronidazole
The FDA has approved Likmez, a liquid oral formulation of metronidazole (ATI-1501), an antibiotic used to treat a wide variety of infections. Currently Likmez is the only liquid oral suspension of metronidazole approved in the US. Likmez, manufactured by the Canadian company Appili has been licensed to Saptalis for commercialization in the US and elsewhere. According to a press release from Appili, the current tablet form of metronidazole is the only other approved oral form on the US market, but its bitter taste and lack of appropriate dosage forms for patients with difficulty swallowing often presents treatment compliance challenges. They note that “Likmez provides a convenient alternative for patients who have difficulty taking solid oral medicines.” Over 10 million metronidazole prescriptions are written in the US each year to help treat parasitic and anaerobic bacterial infections. The approval will secure patent coverage for the antibiotic through 2039.
DNA Test for Hereditary Cancers
The FDA granted de novo marketing authorization for the Invitae Common Hereditary Cancers Panel, an in vitro diagnostic test that can help detect hundreds of genetic variants associated with an elevated risk of developing certain cancers. The test can also help identify potentially cancer-associated hereditary variants in individuals with already-diagnosed cancer. This test is the first of its kind to be granted FDA marketing authorization. It evaluates DNA extracted from a blood sample to identify variants in 47 genes known to be associated with an elevated risk of developing certain types of cancer, including BRCA1 and 2 involved in breast cancer. The specimen is collected at the point of care, such as a doctor’s office and then sent to a lab for analysis. To validate the test, the manufacturer Invitae tested over 9,000 clinical samples, and showed a greater than or equal to 99.0% accuracy for all tested variant types.
Tofidence (Actemra [toclizumab] Biosimilar)
The FDA has approved Tofidence (tocilizumab-bavi) intravenous formulation, the first biosimilar monoclonal antibody referencing Actemra. The Tofidence intravenous formulation is approved for the treatment of moderately to severely active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and systemic juvenile idiopathic arthritis. Biogen and Bio-Thera entered into a commercialization and license agreement for Tofidence in April 2021. A biosimilar is a biologic that is highly similar to and has no clinically meaningful differences in terms of safety, purity, and potency (safety and effectiveness) from an existing FDA-approved biologic—in this case Actemra—which is called a reference product.
https://www.globenewswire.com/news-release/2023/09/29/2752273/0/en/FDA-Approves-Biogen-s-TOFIDENCE-tocilizumab-bavi-a-Biosimilar-Referencing-ACTEMRA.html
Pombiliti + Opfolda for Pompe Disease
The FDA has approved a two-component therapy, Pombiliti (cipaglucosidase alfa-atga) + Opfolda (miglustat), for the treatment of adults diagnosed with Pompe disease. Pompe disease is a rare inherited lysosomal disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA), resulting in a buildup of glycogen in the lysosomes of muscle cells. Disease severity ranges from skeletal muscle weakness to progressive respiratory effects, such as impaired breathing. Pombiliti, is a recombinant human GAA enzyme expressed with high levels of bis-mannose 6-phosphate, which increases uptake into muscle cells. The recently approved treatment is paired with Opfolda, an enzyme stabilizer, designed to reduce loss of enzyme activity in the blood. The FDA approval was based on data from the Phase III PROPEL trial, with results showing improvements in patients completing a six-minute walk test compared to the standard form of treatment.
https://ir.amicusrx.com/news-releases/news-release-details/amicus-therapeutics-announces-fda-approval-and-launch-new
Subcutaneous Entyvio (Vedolizumab) for Moderate-to-Severe Ulcerative Colitis
The FDA has approved a subcutaneous administration of Entyvio (vedolizumab) for maintenance therapy in adults with moderately to severely active ulcerative colitis (UC) after induction therapy with intravenous Entyvio. Entyvio is a humanized monoclonal antibody to alpha4beta7 integrin and limits the ability of certain white blood cells to infiltrate gut tissues. Entyvio was first approved as an intravenous formulation in 2014 and is currently indicated for both moderate-to-severe ulcerative colitis and moderate-to-severe Crohn’s disease. The manufacturer Takeda was granted the most recent approval for subcutaneous maintenance therapy based on data from the phase 3 VISIBLE 1 study, which showed that 46% of patients receiving subcutaneous Entyvio achieved clinical remission compared to 14% of patients receiving placebo (P < .001).
https://content.takeda.com/?contenttype=PI&product=ENTY&language=ENG&country=USA&documentnumber=1
Experimental Stromal Cell Platform in Mild-To-Moderate ALS
An FDA Advisory committee voted that NurOwn BrainStorm Cell Therapeutics’ stromal cell therapy did not demonstrate substantial evidence of effectiveness for treatment of mild to moderate amyotrophic lateral sclerosis (ALS). The Cellular, Tissue, and Gene Therapies Advisory Committee found that the data were not sufficient in demonstrating efficacy as a treatment for patients with mild-to-moderate ALS. The FDA typically, although not always, follows the ruling of their advisory committee. The agency is expected to make a final decision on the treatment by the scheduled PDUFA date of December 8, 2023. At the meeting this week, the committee voted 17-1-1 (17 No; 1 Yes; 1 Abstain) that the evidence presented did not adequately establish NurOwn as an effective treatment in mild-to-moderate ALS. NurOwn makes use of a platform of autologous mesenchymal stromal cells secreting neurotrophic factors (MSC-NTF). According to a press release from BrainStorm Cell Therapeutics, “the totality of data presented for NurOwn [at the meeting] provide a compelling case for approval, with clinical evidence in those with less advanced disease supported by strong and consistent biomarker data that are predictive of clinical response.” BrainStorm has said that they plan to conduct a randomized, controlled phase 4 study with long-term open-label extension to assess the efficacy and safety of NurOwn and aims to enroll participants in the first half of 2024.
https://ir.brainstorm-cell.com/2023-09-27-BrainStorm-Cell-Therapeutics-Provides-Update-on-FDA-Advisory-Committee-Meeting-to-Review-NurOwn-for-the-Treatment-of-ALS
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