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FDA Action Update, March 2025: Approvals, Closure, and Acceptance
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Key Takeaways
- Tenecteplase was approved for acute ischemic stroke, showing noninferiority to alteplase in the AcT trial, with a faster administration method.
- Eculizumab received expanded approval for pediatric myasthenia gravis, becoming the first treatment for this population, supported by adult and pediatric trial data.
Catch up on any of the neurology news headlines you may have missed over the course of March 2025, compiled all into one place by the NeurologyLive® team.
The FDA was busy in March 2025, making a number of decisions on potential new therapeutic agents including granting approvals, an acceptance, an expanded indication, and closing a inspection site.
With all the treatments that have progressed through the pipeline of clinical development, the NeurologyLive® team has been hard at work covering all the agency movements to make sure you are up to date on the latest news in neurology. To give you a chance to catch up on any of the headlines you may have missed over the course of the last month, we’ve compiled all the updates into one place. The coverage includes the latest FDA approvals, new designations, submissions and resubmissions, and clinical trial initiations and holds.
Click the read more buttons for more details and information about each update.
FDA Approves Tenecteplase for Acute Ischemic Stroke
Early in the month, on March 3, the FDA approved tenecteplase (TNKase; Genentech) for the treatment of acute ischemic stroke (AIS) in adults, according to a Genentech announcement.1 The thrombolytic medicine is an intravenous (IV) tissue plasminogen activator that is clot-dissolving, administered as a single 5-second IV bolus. The company noted that it will be providing a 25-mg vial configuration in the coming months to support the approval.
Tenecteplase’s approval was based on the data collected from the phase 3 AcT trial (NCT03889249), which enrolled 1600 patients and compared outcomes between patients treated with the new therapy compared with alteplase. The data showed that 36.9% of those treated with tenecteplase (296 of 802) reported modified Rankin Scores (mRS) of 0-1 in the 90- to 120-day window compared with 34.8% of the alteplase group (266 of 765), showing noninferiority and an unadjusted risk difference of 2.1% (95% CI, –2.6 to 6.9).2
“Today’s approval is a significant step forward and underscores our commitment to advancing stroke treatment options for patients. TNKase provides a faster and simpler administration, which can be critical for anyone who is dealing with an acute stroke,” Levi Garraway, MD, PhD, the chief medical officer and head of Global Product Development at Genentech, said in a statement.1
FDA Closes Inspection of Site for Phase 3 TRANQUILITY II Trial of BXCL501 in Alzheimer Agitation
On the same day, March 3, the FDA closed its inspection of a single site in the phase 3 TRANQUILITY II trial (NCT05271552) under 21 C.F.R. 20.64(d)(3) and issued the Establishment Inspection Report, designating the site with a status of “Voluntary Action Indicated.”3
TRANQUILITY is a double-blind, placebo-controlled trial assessing the therapeutic potential of BXCL501 (BioXcel Therapeutics), an investigational proprietary, orally dissolving film formulation of dexmedetomidine, as a potential treatment for Alzheimer disease (AD) agitation. For context, in October 2023, BioXcel conducted an independent audit after the drugmaker disclosed that a principal investigator involved in the study was under investigation in a regulatory filing. According to the SEC filing, the same investigator was being accused of fabricating an email correspondence related to the reported timing of a serious adverse event (AE) as required in the study protocol.
"We believe this report and the closing of the investigation, together with the positive findings from the independent audit we announced in October 2023, further reaffirm the data integrity from the single site and the body of clinical evidence we intend to include in a potential sNDA submission," Vimal Mehta, PhD, chief executive officer at BioXcel, said in a statement.3 "We have already received FDA feedback on the protocol for our TRANQUILITY In-Care Phase 3 trial and look forward to advancing this program with our lead neuroscience asset BXCL501."
FDA Approves Expanded Use of Eculizumab for Pediatric Myasthenia Gravis
A day later, on March 4, the FDA granted approval for an expanded indication of eculizumab (Soliris; Alexion/AstraZeneca) to include both adult and pediatric patients who are 6 years of age or older with generalized myasthenia gravis (gMG) who are antiacetylcholine receptor (AChR) antibody positive. With the approval, it becomes the first and only treatment for pediatric patients living with the disease.4
The use of eculizumab in pediatric patients for this indication was supported by evidence from a well-controlled trial in adults with additional pharmacokinetic and safety data in pediatric patients with gMG who are 12 years of age and older, as well as pharmacokinetic and safety data in other pediatric populations in the range of at least 6 years to younger than 12 years. In a 26-week, single-arm study of 11 pediatric patients with gMG 12 to 17 years of age, adverse reactions were consistent with those observed in adults living with the disease.
In terms of administration, eculizumab is given by an intravenous infusion over 35 minutes to adults and 1 to 4 hours in pediatric patients via gravity feed, a syringe-type pump, or an infusion pump. The injection is administered in doses of 300 mg/30 mL (10 mg/mL) as a clear, colorless solution in a single-dose vial. It remains contraindicated for patients with unresolved serious Neisseria meningitidis infection.
FDA Approves Vutrisiran for ATTR-CM, Expanding Indication in Amyloidosis
A couple of weeks later, on March 20, the FDA approved vutrisiran (Amvuttra; Alnylam Pharmaceuticals) for the treatment of cardiomyopathy associated with wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults.5
This expanded indication makes vutrisiran both the first and the only FDA-approved therapy for both the cardiomyopathy and polyneuropathy manifestations of ATTR amyloidosis. Alnylam also noted it plans to offer patient access programs to minimize out-of-pocket costs, with the company anticipating that most patients will pay $0.
The approval decision was made based on positive findings from the HELIOS-B phase 3 clinical trial (NCT04153149), which evaluated the RNA interference (RNAi) therapeutic’s safety and efficacy in a patient population of 655 patients who were randomly assigned to 25-mg vutrisiran (n= 326) or placebo (n = 329), with a subgroup of monotherapy patients who were not receiving tafamidis (Vyndamax; Pfizer) at baseline. Those receiving vutrisiran demonstrated statistically significant reductions in cardiovascular mortality, hospitalizations, and urgent heart failure visits compared with those on placebo. Altogether, the study met all 10 of its prespecified primary and secondary end points.
FDA Accepts Regulatory Submission for BTK Inhibitor Tolebrutinib for Non-Relapsing Secondary Progressive MS
A few days later, on March 25, the FDA accepted Sanofi’s regulatory submission for tolebrutinib as a potential treatment for patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS) and to slow disability accumulation independent of relapse activity in adults, assigning the agent a PDUFA target date of September 28, 2025. If approved, tolebrutinib would become the first and only brain-penetrant Bruton tyrosine kinase (BTK) inhibitor marketed for the treatment of MS, and the first specific for nrSPMS.6
Tolebrutinib, an oral, brain-penetrant therapy designed to target smoldering neuroinflammation, remains under review in the European Union as well. The regulatory submissions for the agent were based on findings from the phase 3 HERCULES study (NCT04411641) in nrSPMS and 2 phase 3 studies (GEMINI 1 [NCT04410978] and GEMINI 2 [NCT04410991]) in relapsing MS. In addition, it remains in development for patients with primary progressive MS, with ongoing study results from the phase 3 PERSEUS trial (NCT04458051) anticipated later this year.
"The totality of data across our clinical program validates our scientific understanding of smoldering neuroinflammation as a distinct inflammatory process in MS," Erik Wallström, MD, PhD, global head of neurology department at Sanofi, said in a statement.6 "People living with non-relapsing secondary progressive multiple sclerosis or who experience disability independent of relapse activity suffer from disability that worsens over time due to persistent inflammation in the brain, known as smoldering neuroinflammation, which is the primary driver of disability. The demonstrated ability of tolebrutinib to delay disability by targeting underlying drivers of the disease represents a potential paradigm shift in treating these patients."
FDA Approves Diazoxide Choline Extended-Release Tablets for Hyperphagia in Prader-Willi Syndrome
A day later, on March 26, the FDA approved Soleno Therapeutics' diazoxide choline (DCCR) extended-release tablets, marketed as Vykat XR, for the treatment of Prader-Willi syndrome (PWS) for patients 4 years and older who have hyperphagia. Thus, DCCR, a novel, proprietary extended-release dosage form containing diazoxide choline — the crystalline salt of diazoxide — is administered once daily and becomes the first therapy to treat hyperphagia in PWS.7
In November 2024, the FDA extended its review period for the new drug application (NDA) of DCCR extended-release tablets for PWS.8 The extension was triggered by recent responses to the agency's information requests, which were classified as a major amendment to the NDA. As a result, the PDUFA goal date was pushed back by 3 months to allow the FDA sufficient time to complete its review, including the newly submitted data. Notably, the agency did not highlight any concerns related to safety, efficacy, or manufacturing in its correspondence.
“My immediate reaction was relief - I have been working with PWS for [over] 25 years to try to find an answer to the life-limiting issue of hyperphagia in this syndrome, so I was grateful that we now have an effective medication. I was one of the [principal investigators] for the study and had 33 patients on trial at my site, so got to see firsthand how well this medication worked for patients,” Jennifer Miller, MD, professor of pediatric endocrinology at the University of Florida, told NeurologyLive® in a recent interview. "I think it will change the treatment landscape by offering hope to patients and families with this condition. The concept of having a starving child and not being able to feed them is devastating for parents to contemplate. For physicians it offers the possibility of treatment in a space where there is currently none. That is huge."
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