FDA Issues Complete Response Letter for GTx-104 in Patients With Aneurysmal Subarachnoid Hemorrhage

Nearly 10 months after the submission of a new drug application (NDA), the FDA has issued a complete response letter (CRL) for Grace Therapeutics’ GTx-104, an injectable formulation of nimodipine, for the treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). The administration referenced items in the chemistry, manufacturing, and Controls (CMC) and non-clinical sections of the application.¹

The cited items are related to leachables data for product packaging, non-clinical product toxicology risk assessments, and product manufacturing deficiencies at Grace Therapeutics’ contract manufacturing organization. The company stated in a press release that it believes it can address the CRL in a resubmission of its NDA and intends to request a Type A meeting with the FDA to clarify the path forward and determine the appropriate next steps.

“Potential FDA approval of our NDA for GTx-104 for the treatment of aSAH would represent the first meaningful innovation in the standard of care for these patients in more than 40 years,” Prashant Kohli, MD, chief executive officer of Grace Therapeutics, said in a statement.¹ “We are confident in the robust data package supporting our NDA submission, and that the CMC issues identified by the FDA can be successfully addressed in our resubmission.”

GTx-104 is administered intravenously and is designed to improve ease of use in the acute care setting, potentially eliminating the need for nasogastric tube administration in unconscious or dysphagic patients. The agent, which was most recently evaluated in a phase 3 study, may reduce food effects, drug–drug interactions, and dosing variability, according to Grace. In addition, the company noted that GTx-104 may offer improved management of hypotension in patients with aSAH.²

The NDA of GTx-104 was supported by findings from the phase 3 STRIVE-ON study (NCT05995405), a prospective, randomized, open-label study comparing GTx-104 to oral nimodipine in patients hospitalized with aSAH. The trial, which featured 50 patients on GTx-104 and 52 on oral nimodipine, met its primary end point, with a 19% reduction of at least 1 incidence of clinically significant hypotension observed in the GTx-104 group relative to oral nimodipine.²

Safety data from STRIVE-ON showed a comparable number of adverse events (AEs) between the 2 arms, as well as no new safety signals for GTx-104. Of note, there were 8 deaths in the GTx-104 arm and 4 deaths in the oral nimodipine arm; however, all were attributed to the severity of the patient’s underlying disease. None of the deaths were determined to be related to the investigational drug or the comparator.

In STRIVE-ON, each patient was evaluated for up to 90 days inclusive of the 21-day treatment period. At the conclusion of the study, results showed a higher proportion of the most severe cases of aSAH (Hunt & Hess Grade V) with the worst prognosis in the GTx-104 arm (8%) compared with the oral nimodipine arm (2%). More notably, those on GTx-104 experienced fewer intensive care unit readmissions, ICU days, and ventilator days compared with oral nimodipine.

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There were several other measures in STRIVE-ON that favored or were comparable to GTx-104. This included relative dose intensity, where 54% of GTx-104-treated patients had RDIs of 95% or higher of the prescribed dose compared with 8% of those on oral nimodipine. In addition, investigators recorded a 29% relative increase in the number of patients receiving GTx-104 with favorable outcomes at 90 days follow-up on the modified Rankin scale.

GTx-104 was also previously studied in a single-center, pharmacokinetic bridging trial. In this two-period crossover study, 58 patients received IV GTx-104 followed by oral nimodipine, or vice versa, over a 72-hour period. The primary PK end point, maximum concentration (Cmax) during the first four hours on day 1, was 92% (90% CI, 82–104), whereas the area under the curve (AUC), reflecting total drug exposure by day 3, was 106% (90% CI, 99–114).³

REFERENCES
1. Grace Therapeutics Provides Regulatory Update on New Drug Application for GTx-104. Grace Therapeutics. News Release. April 23, 2026. Accessed: April 23, 2026. https://www.gracetx.com/investors/news-events/press-releases/detail/303/grace-therapeutics-provides-regulatory-update-on-new-drug-application-for-gtx-104
2. Grace Therapeutics Announces Results From Pivotal Phase 3 STRIVE-ON Safety Trial of GTx-104 in aSAH. News release. Grace Therapeutics. February 10, 2025. Accessed June 25, 2025. https://www.gracetx.com/investors/news-events/press-releases/detail/282/grace-therapeutics-announces-results-from-pivotal-phase-3-strive-on-safety-trial-of-gtx-104-in-asah
3. Acasti Pharma announces positive results for pharmacokinetic bridging study, with intravenous GTX-104 meeting all endpoints. News release. Acasti Pharma. May 18, 2022. Accessed June 25, 2025. https://www.globenewswire.com/en/news-release/2022/05/18/2445894/0/en/Acasti-Pharma-Announces-Positive-Results-for-Pharmacokinetic-Bridging-Study-With-Intravenous-GTX-104-Meeting-All-Endpoints.html