Lack of resources at FDA extends clinical hold on ALS drug NUZ-001
Decision now due in October; developer calls delay 'extremely disappointing'
Due to a lack of resources and personnel, the U.S. Food and Drug Administration (FDA) has delayed its decision on whether or not to lift the clinical hold on NUZ-001, Neurizon Therapeutics’ investigational therapy for amyotrophic lateral sclerosis (ALS), the developer announced.
A decision from the regulatory agency is now due by Oct. 3, according to a company press release.
Regulators had placed the clinical hold earlier this year, citing a need for more preclinical studies before a planned NUZ-001 arm of the HEALEY ALS platform trial (NCT04297683) — a perpetual multicenter, multiregimen clinical trial testing treatment candidates for ALS — could proceed.
Neurizon had aligned with the FDA on its strategy to address that need earlier this summer, and submitted data from the studies in the form of a clinical hold complete response (CHCR) just weeks later.
The FDA usually makes a decision on a CHCR within a month, so the company had anticipated the hold being lifted by the end of August, allowing participation in the HEALEY trial to start by year’s end. But agency-wide restructuring and staffing reductions have caused backups at the FDA and, in this case, a delay not related to the company’s submission on NUZ-001, according to Neurizon.
“This delay is not a reflection on the quality or completeness of Neurizon’s submission but rather the result of broader strain in the FDA’s capacity … under recent administrative reforms,” the release stated.
Michael Thurn, PhD, managing director and CEO of Neurizon, called the delay “extremely disappointing — particularly given the straightforward nature of the information provided in our response.”
Nonetheless, Thurn said the company “[remains] confident in the potential of NUZ-001 as a transformative therapy for ALS.”
Thurn also said Neurizon is “committed to pursuing every possible avenue to accelerate timelines.”
To that end, the company is engaging with key opinion leaders and patient advocacy groups in the U.S. to advocate for an expedited review in light of the “critical and urgent unmet need in ALS,” according to the CEO.
“Our mission remains unchanged: to deliver hope and innovative solutions to patients and families living with neurodegenerative diseases, with diligence, transparency, and unwavering focus,” he said.
Main ingredient in NUZ-001 is deworming agent used by vets
In ALS, the nerve cells that control muscle movements are progressively lost. The toxic accumulation of faulty protein clumps is one mechanism through which this is thought to occur.
The active ingredient in NUZ-001 is monepantel, an oral deworming agent commonly used in veterinary medicine. An off-target effect of monepantel is that it inhibits the mTOR signaling pathway that normally regulates autophagy, a cellular process through which unneeded or damaged components are broken down and recycled.
By boosting autophagy, NUZ-001 may help clear the toxic proteins that are believed to contribute to ALS progression, according to the developer.
Data from the Australia-based Phase 1 MEND trial (NCT04894240) and its open-label extension study (NCT06177431), both now complete, showed that daily NUZ-001 slowed disease progression and extended survival relative to an external control group of untreated participants from a large ALS database. The therapy also was found to slow lung function declines among patients.
NUZ-001 was selected last summer for participation in HEALEY, a U.S.-based Phase 2/3 study designed to simultaneously test multiple investigational ALS therapies against a shared placebo group.
Neurizon waiting for lift of clinical hold to start in HEALEY trial
Neurizon then filed an application with the FDA seeking to conduct clinical studies of NUZ-001 in the U.S. Regulators placed the clinical hold shortly thereafter, citing a need for more studies on the therapy’s pharmacological properties in animals.
The studies to address those concerns evaluated how NUZ-001 moves through the body in rats and dogs. The data enhanced confidence in the dose selection and tolerability profile needed to move forward with clinical testing, according to Neurizon.
The FDA has acknowledged persistent resourcing challenges, which have been exacerbated by organisational changes implemented under the current administration, resulting in increased review backlogsclini.
Neurizon also recently entered into a global licensing deal with Elanco Animal Health, a company that produces medications for pets and livestock, to advance the development of NUZ-001. In addition to providing Neurizon with a long-term supply of monepantel, Elanco was to allow Neurizon access to its extensive data on monepantel’s use in animals to support regulatory requirements.
Recent regulatory delays are not unique to NUZ-001. Other ALS programs, including one from Coya Therapeutics, have been similarly affected by the strain on the FDA. Coya’s application seeking clinical trial clearance for its ALS treatment candidate COYA-302 has also been deferred.
“The delay follows a broader pattern in the sector, with other sponsors experiencing extended review timelines,” Thurn said. “The FDA has acknowledged persistent resourcing challenges, which have been exacerbated by organisational changes implemented under the current administration, resulting in increased review backlogs.”
About the Author
