5 First-in-Class, First-in-Disease FDA Approvals From August

August was another busy month for the FDA, which approved several groundbreaking therapies, including first-in-class and first-in-disease treatments across various conditions.

Here are 5 of the most notable August FDA approvals:

From respiratory conditions to rare diseases and beyond, here are 5 groundbreaking FDA approvals from last month. | Image Credit: Tada Images - stock.adobe.com .jpeg

FDA Approves Dordaviprone as First and Only Treatment for Aggressive Form of Glioma

On August 6, the FDA granted accelerated approval to dordaviprone (Modeyso; Jazz Pharmaceuticals), making it the first and only approved therapy for recurrent H3 K27M-mutant diffuse midline glioma, an ultra-rare, aggressive brain tumor primarily affecting children and young adults.¹ It is indicated for adult and pediatric patients aged 1 year and older with progressive disease following prior therapy.

The approval was supported by an efficacy analysis of 50 patients with recurrent H3 K27M-mutant diffuse midline glioma enrolled in 5 open-label clinical trials: ONC006 (NCT02525692), ONC013 (NCT03295396), ONC014 (NCT03416530), ONC016 (NCT05392374), and ONC018 (NCT03134131). Using Response Assessment in Neuro-Oncology (RANO) 2.0 criteria, the overall response rate was 22% (95% CI, 12%-36%), as assessed by blinded independent central review.

The median duration of response was 10.3 months (95% CI, 7.3-15.2), with 73% of patients maintaining their response for at least 6 months and 27% for at least 12 months. The pooled analysis also showed a median time of response of 8.3 months (range, 1.9-15.9) with dordaviprone.

"This approval represents a long-awaited treatment option for families affected by H3 K27M-mutant diffuse midline glioma," David F. Arons, president and chief executive officer of the National Brain Tumor Society, said in a statement.² "…For years, this diagnosis has lacked an approved treatment, and today, that changes. Families finally have a treatment option and a reason to believe in more time together to make memories that might not have otherwise been possible."

Brensocatib Becomes First FDA-Approved Therapy for Bronchiectasis

The FDA’s approval of brensocatib (Brinsupri; Insmed) on August 12 makes it both the first approved therapy for patients with non–cystic fibrosis bronchiectasis and the first dipeptidyl peptidase 1 (DPP1) inhibitor approved to treat a neutrophil-mediated disease.³ The small-molecule, oral, reversible DPP1 inhibitor reduces the activation of neutrophil serine proteases, which drive inflammation and tissue damage in chronic lung diseases.

This approval was based on data from the ASPEN trial (NCT04594369), a phase 3, double-blind trial. Of the 1721 enrolled patients, 583 received 10 mg of brensocatib, 575 received 25 mg, and 563 received a placebo.

Annualized pulmonary exacerbation rates were 1.02 with 10 mg, 1.04 with 25 mg, and 1.29 with placebo, yielding rate ratios (RRs) of 0.79 (95% CI, 0.68-0.92; adjusted P = .004) for 10 mg and 0.81 (95% CI, 0.69-0.94; adjusted P = .005) for 25 mg vs placebo. At week 52, 48.5% of patients treated with brensocatib remained exacerbation-free vs 40.3% treated with placebo. The RRs for remaining exacerbation-free were 1.20 (95% CI, 1.06-1.37; adjusted P = .02) for 10 mg and 1.18 (95% CI, 1.04-1.34; adjusted P = .04) for 25 mg.

“[Brensocatib is] the first treatment that targets neutrophilic inflammation, which is the underlying driving force for a lot of exacerbations,” James D. Chalmers, MBChB, PhD, ASPEN trial lead investigator, said in an interview with The American Journal of Managed Care^® (AJMC^®).⁴ “I think it will add a very important additional tool on top of those other therapies that we currently use for people with bronchiectasis.”

FDA Approves Zopapogene Imadenovec for Recurrent Respiratory Papillomatosis

On August 19, the FDA approved zopapogene imadenovec-drba (Papzimeos; Precigen) as the first and only treatment for adult patients with recurrent respiratory papillomatosis (RRP), a rare upper- and lower-respiratory tract disease caused by human papillomavirus (HPV).⁵

Zopapogene imadenovec-drba is a nonreplicating adenoviral vector-based immunotherapy that expresses a fusion antigen made up of selected regions of HPV types 6 and 11. It is administered via 4 subcutaneous injections over a 12-week interval.

This approval was based on data from an open-label, single-arm, pivotal study (NCT04724980), which met its primary safety and prespecified efficacy end points. Of 35 patients treated at the recommended phase 2 dose (5x10¹¹ particle units), 18 (51%) experienced a complete response (CR; 95% CI, 34-69). However, the median duration of CR had not yet been reached.

"This long-awaited FDA approval represents a momentous milestone for the RRP community," Kim McClellan, president of the Recurrent Respiratory Papillomatosis Foundation, said in a press release.⁶ "For the first time, adult patients with RRP have access to an FDA-approved therapy that offers the potential to reduce—or even eliminate—endless repeated surgeries."

FDA Approves First RNA-Targeted Treatment for Hereditary Angioedema

The FDA approved donidalorsen (Dawnzera; Ionis Pharmaceuticals, Inc.), an RNA-targeted prophylactic treatment, on August 21 for hereditary angioedema (HAE), a genetic disorder that affects different parts of the body via fluid buildup in tiny blood vessels, which can prevent blood and lymph from moving throughout the body.⁷ This approval makes donidalorsen the only treatment of its kind to help prevent HAE attacks in patients aged 12 years and older.

Donidalorsen is self-administered in 80-mg doses through a subcutaneous autoinjector and can be taken every 4 or 8 weeks. Its approval was based on the results of the phase 3 OASIS-HAE trial (NCT05139810), in which 45 patients received the dose every 4 weeks and 23 did so every 8 weeks.

The monthly HAE attack rate decreased by 81% (95% CI, 65%-89%) through 24 weeks among patients who took donidalorsen every 4 weeks. Similarly, the median reduction in attack rate from baseline was 90% in those who received the medication every 4 weeks.

In comparison, the mean attack rate for participants taking the dose every 8 weeks was 55% lower (95% CI, 22%-74%) compared with placebo. Also, the median reduction in attack rate was 83% compared with only 16% in the placebo group. The results among both donidalorsen groups prove that it was effective in reducing the number of HAE attacks.

“[Donidalorsen] represents a significant advance for people living with HAE who need improved treatment options,” Brett P. Monia, PhD, CEO of Ionis, said in a statement.⁸ “With strong and durable efficacy, convenient administration, and the longest dosing option available, we believe [donidalorsen] will be the prophylactic treatment of choice for many people living with HAE.”

Rilzabrutinib Becomes First FDA-Approved BTK Inhibitor for ITP

On August 30, the FDA approved rilzabrutinib (Wayrilz; Sanofi) as a first-in-class treatment for immune thrombocytopenia (ITP), a rare autoimmune disorder⁹; it is the first Bruton tyrosine kinase (BTK) inhibitor approved for this patient population. Because BTK plays a central role in the inflammatory pathways involved in ITP, rilzabrutinib, which selectively inhibits it, may reduce disease activity while minimizing the risk of off-target adverse effects.

This decision was based on results from the phase 3 LUNA 3 study (NCT04562766), in which participants received 400 mg of oral rilzabrutinib twice daily or placebo during a 12- to 24-week double-blind period, followed by a 28-week open-label phase and a 4-week safety follow-up or long-term extension period. The trial’s primary end point was durable platelet response, defined as achieving platelet counts at or above 50,000/μL for at least 8 of the last 12 weeks of the double-blind period without rescue therapy.

Of the adult patients analyzed, 133 received rilzabrutinib and 69 received a placebo. At week 25, a durable platelet response was achieved in 23% (n = 31) of patients receiving rilzabrutinib and 0% of those on placebo (P < .0001). Based on data from both study periods, a durable response was achieved in 29% (n = 38) of patients treated with rilzabrutinib.

"With its differentiated mechanism of action, Wayrilz has the potential to become a treatment of choice for immune thrombocytopenia patients who have not responded to a prior therapy," Brian Foard, executive vice president and head of specialty care at Sanofi, said in a statement.¹⁰

References

1. McNulty R. FDA approves dordaviprone as first and only treatment for aggressive form of glioma. AJMC. August 6, 2025. Accessed September 12, 2025. https://www.ajmc.com/view/fda-approves-dordaviprone-as-first-and-only-treatment-for-aggressive-form-of-glioma
2. Jazz Pharmaceuticals announces U.S. FDA approval of Modeyso (dordaviprone) as the first and only treatment for recurrent H3K27M-mutant diffuse midline glioma. News release. Jazz Pharmaceuticals. August 6, 2025. Accessed September 12, 2025. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval-modeysotm
3. McCormick B. Brensocatib becomes first FDA-approved therapy for bronchiectasis. AJMC. August 12, 2025. Accessed September 12, 2025. https://www.ajmc.com/view/brensocatib-becomes-first-fda-approved-therapy-for-bronchiectasis
4. McCormick B, Chalmers JD. Brensocatib becomes first approved therapy for bronchiectasis, expanding treatment options: James D. Chalmers, MBChB, PhD. AJMC. August 20, 2025. Accessed September 12, 2025. https://www.ajmc.com/view/brensocatib-becomes-first-approved-therapy-for-bronchiectasis-expanding-treatment-options-james-d-chalmers-mbchb-phd
5. McNulty R. FDA approves zopapogene imadenovec for recurrent respiratory papillomatosis. AJMC. August 19, 2025. Accessed September 12, 2025. https://www.ajmc.com/view/fda-approves-zopapogene-imadenovec-for-recurrent-respiratory-papillomatosis
6. Precigen announces full FDA approval of Papzimeos (zopapogene imadenovec-drba), the first and only approved therapy for the treatment of adults with recurrent respiratory papillomatosis. News release. Precigen. August 15, 2025. Accessed September 12, 2025. https://investors.precigen.com/news-releases/news-release-details/precigen-announces-full-fda-approval-papzimeos-zopapogene
7. Bonavitacola J. FDA approves first RNA-targeted treatment for hereditary angioedema. August 21, 2025. Accessed September 12, 2025. https://www.ajmc.com/view/fda-approves-first-rna-targeted-treatment-for-hereditary-angioedema
8. Dawnzera (donidalorsen) approved in the US as first and only RNA-targeted prophylactic treatment for hereditary angioedema. News release. Business Wire. August 21, 2025. Accessed August 21, 2025. https://www.businesswire.com/news/home/20250818615141/en/DAWNZERA-donidalorsen-approved-in-the-U.S.-as-first-and-only-RNA-targeted-prophylactic-treatment-for-hereditary-angioedema
9. McCormick B. Rilzabrutinib becomes first FDA-approved BTK inhibitor for ITP. AJMC. August 30, 2025. Accessed September 12, 2025. https://www.ajmc.com/view/rilzabrutinib-becomes-first-fda-approved-btk-inhibitor-for-itp
10. ASH: rilzabrutinib demonstrated significant patient benefit in the first positive phase 3 study of a BTK inhibitor in ITP. News release. Sanofi. December 7, 2024. Accessed August 30, 2025. https://www.sanofi.com/en/media-room/press-releases/2024/2024-12-07-16-30-00-2993342