FDA approvals: August 2025

ByHeather

This month the FDA approved 4 new drugs.

Modeyso (dordaviprone)

  • Manufacturer: Jazz Pharmaceuticals
  • Condition approved for: To treat diffuse midline glioma (DMG) harboring an H3 K27M mutation with progressive disease following prior therapy. Diffuse midline glioma is a a type of brain tumor common in children and young adults that is characterized by rapid progression. H3 refers to histone 3. Histones are proteins that help give chromosomes their shapes. K27M refers to the specific amino acid that has been changed. In this case, the 27th amino acid has been changed from lysine (K) to methionine (M). This mutation in tumor cells leads to aggressive growth and resistance to most lines of therapy.
  • How it works: Dordaviprone works on DMG by potent agonist of the ATP-dependent Clp protease proteolytic subunit (ClpP), a mitochondrial protease that degrades mitochondrial respiratory chain proteins to disrupt energy homeostasis.
  • Why it’s cool: This is a first of its kind treatment. Modeyso received accelerated approval due to the nature of the disease it’s treating. Because DMG tends to be resistant to most other treatments, it’s exciting to have a potential treatment that will be more effective.
Evangeline R Jackson, Mika L Persson, Cameron J Fish, Izac J Findlay, Sabine Mueller, Javad Nazarian, Esther Hulleman, Jasper van der Lugt, Ryan J Duchatel, Matthew D Dun, A review of current therapeutics targeting the mitochondrial protease ClpP in diffuse midline glioma, H3 K27-altered, Neuro-Oncology, Volume 26, Issue Supplement_2, April 2024, Pages S136–S154,

Hernexeos (zongertinib)

  • Manufacturer: Boehringer Ingelheim
  • Condition approved for: To treat adults with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.
  • How it works: Zongertinib is a covalent inhibitor that forms a covalent bond between its acrylamide moiety and cysteine 805 of HER2. HER2 is a protein found on the surface of cells and plays a major role in growth and division. By binding to HER2, zongertinib inhibits cell proliferation.
  • Why it’s cool: Hernexeos is the first orally available treatment for NSCLC with HER2 mutation. NSCLC with HER2 mutations are more likely to metastasize and have poorer prognosis than NSCLC without HER2 mutations.
  • B. Wilding, et al.. Zongertinib (BI 1810631), an irreversible HER2 TKI, spares EGFR signaling and improves therapeutic response in preclinical models and patients with HER2-Driven cancers. Cancer Discov., 15 (1) (2025), pp. 119-138
  • https://www.boehringer-ingelheim.com/human-health/cancer/lung-cancer/fda-approval-hernexeos-first-oral-treatment-her2-mutant-advanced-nsclc

Brinsupri (brensocatib)

  • Manufacturer: Insmed
  • Condition approved for: To treat non-cystic fibrosis bronchiectasis. Bronchiectasis is a condition where the airways become permanently widened and thickened leading to inflammation and mucus buildup.
  • How it works: Brensocatib is a dipeptidyl Peptidase 1 Inhibitor that blocks the activation of neutrophil serine proteases (NSPs). NSPs are a family of enzymes found in the granules of neutrophils. NSPs, specifically, neutrophil elastase, cathepsin G, and proteinase 3 are believed to be key factors in the pathogenesis of chronic inflammatory diseases like bronchiectasis. In patients with bronchiectasis, lower levels of sputum neutrophil elastase is associated with a reduction in pulmonary exacerbations.
  • Why it’s cool: Brinsupri is a first-in-class treatment. There aren’t a lot of option for treatments for bronchiectasis, and they all seem to target the symptoms. Brinsupri targets the cause of the symptoms.
  • Chalmers, J.D., Usansky, H., Rubino, C.M. et al. Pharmacokinetic/Pharmacodynamic Evaluation of the Dipeptidyl Peptidase 1 Inhibitor Brensocatib for Non-cystic Fibrosis Bronchiectasis. Clin Pharmacokinet 61, 1457–1469 (2022).

Dawnzera (donidalorsen)

  • Manufacturer: Ionis Pharmaceuticals
  • Condition approved for: To prevent attacks of hereditary angioedema. Hereditary angioedema is an inherited condition characterized by recurrent episodes of swelling. Hereditary angioedema is caused by a mutation in the C1 inhibitor (C1-INH) gene. C1-INH is a protein that regulates the complement system in the immune response. Mutations can cause deficiency or dysfunction of C1-INH can cause an overactivation of the complement system including the release of bradykinin, a substance that causes swelling.
  • How it works: Donidalorsen is an investigational GalNAc3-conjugated antisense oligonucleotide that binds to prekallikrein mRNA in the liver and reduces the expression of prekallikrein. Admittedly, I am not the most well-versed on mRNA treatments. From what I understand, GalNAC3 is attached to this oligonucleotide (short strand of a specifically designed RNA) to increase its ability to be taken into liver cells. In the liver cell, it binds to the prekallikrein mRNA and reduces the expression of prekallikrein. Prekallikrein is a protein precursor to kallikrein. Kallikrein is an enzyme that causes the release of bradykinin.
  • Why it’s cool: Dawnzera is the first RNA prophylactic treatment for hereditary angioedema. Many treatments for hederditary angioedema focus on acute attacks; however, Dawnzera is one of the few treatments focused on preventing attacks.
  • Riedl MA, Bordone L, Revenko A, Newman KB, Cohn DM. Clinical Progress in Hepatic Targeting for Novel Prophylactic Therapies in Hereditary Angioedema. J Allergy Clin Immunol Pract. 2024 Apr;12(4):911-918.

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