FDA Grants Tinostamustine Orphan Drug Designation for Malignant Gliomas

The investigational, potentially first-in-class agent tinostamustine (EDO-S101) has earned FDA orphan drug designation (ODD) for first-line treatment of malignant gliomas, including the aggressive, difficult-to-treat glioblastoma multiforme (GBM).¹

With incentives such as tax credits, user fee exemptions, and a potential 7 years of market exclusivity upon approval, the FDA’s orphan drug program is intended to spur and facilitate the development of drugs that treat rare conditions affecting fewer than 200,000 people in the US.² The ODD awarded to tinostamustine is a recognition of its potential to treat malignant gliomas, which occur in every 5 of 100,000 individuals in the US.³

"As many as 15,000 people in the US are diagnosed with glioblastoma each year. Unfortunately, there is limited survival benefit with existing treatment options," said Julie Ducharme, vice president and chief scientific officer of Purdue Pharma, in a news release.¹ "This recognition from FDA is an important milestone in our mission of advancing innovative science in areas of serious, unmet medical need. We look forward to further investigating tinostamustine, which has shown promise in early trials."

About Tinostamustine

Tinostamustine is a novel alkylating deacetylase inhibitor molecule fusing the chemotherapy medications bendamustine and vorinostat. Through this fusion, the agent achieves a bifunctional mechanism of action that induces DNA damage and blocks cancer cell repair.^1,4

Tinostamustine has shown promise in preclinical and early clinical studies. For instance, in a phase 1/2 clinical study (NCT03345485) evaluating tinostamustine’s safety, tolerability, pharmacokinetics, and preliminary efficacy in 49 patients with advanced solid tumors, the agent demonstrated a manageable tolerability profile and modest efficacy signals.^5-7 In the phase 2 portion, 2 of 36 efficacy-evaluable patients achieved a partial response, and 14 had stable disease for 4 months or longer.

While brain tumors were not among the tumors studied in the phase 1/2 trial, the global, multiarm, response adaptive randomization platform phase 2/3 GBM AGILE trial (NCT03970447) will be imminently evaluating tinostamustine in adult patients with newly diagnosed or recurrent GBM.⁸

Here, the agent will be assessed against multiple experimental treatment arms and a control arm receiving temozolomide (Temodar), lomustine, and radiation therapy. Arms will be added as new information about promising drugs emerge, and removed based on ongoing evaluations. The study’s primary end point is overall survival; secondary end points include progression-free survival, tumor response, and duration of response.

The study is actively recruiting with an estimated enrollment of 1280 patients and estimated completion date of June 2030.

REFERENCES

1. FDA grants orphan drug designation for tinostamustine in malignant glioma. News release. Business Wire. November 10, 2025. Accessed November 11, 2025. https://tinyurl.com/v4mwa5x3

2. Designating an orphan product: drugs and biological products. US Food & Drug Administration. Updated August 12, 2024. Accessed November 11, 2025. https://tinyurl.com/5n77pu2w

3. Mesti T, Ocvirk J. Malignant gliomas: old and new systemic treatment approaches. Radiol Oncol. 2016;50(2):129-138. doi:10.1515/raon-2015-0003

4. National Center for Biotechnology Information. PubChem compound summary for CID 46836227, tinostamustine. Accessed November 11, 2025. https://tinyurl.com/2ter893e

5. Study of the safety, pharmacokinetics and efficacy of tinostamustine in patients with advanced solid tumors (EDO-S101). ClinicalTrials.gov. Updated October 21, 2024. Accessed November 11, 2025. https://www.clinicaltrials.gov/study/NCT03345485

6. Chugh R, Kummar S, Schneider RE, et al. Results from a phase I/II trial of tinostamustine monotherapy in advanced solid tumours (NCT03345485): safety and efficacy in a subset of patients (pts) with soft tissue sarcoma (STS). Ann Oncol. 2023;34:S1048-S1048. doi:10.1016/j.annonc.2023.09.1186

7. Tinker A, Strauss JF, Schneider R, et al. A phase II study of tinostamustine in patients (pts) with advanced solid tumours. J Clin Oncol. 2023;41(suppl 16):3021. doi:10.1200/jco.2023.41.16_suppl.3021

8. A trial to evaluate multiple regimens in newly diagnosed and recurrent glioblastoma (GBM AGILE). ClinicalTrials.gov. Updated September 9, 2025. Accessed November 11, 2025. https://clinicaltrials.gov/study/NCT03970447