FDA Action Update, February 2022: Approvals, Resubmissions, Application Clearances


Catch up on any of the neurology news headlines you may have missed over the course of the last month, compiled all into one place by the NeurologyLive® team.

Several FDA actions took place in February 2022, including an approved medication to treat spasticity of multiple sclerosis, a resubmission of pimavanserin, and several cleared studies set to get underway in Parkinson disease and Alzheimer disease.

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 detail and information about each update.

FDA Approves Baclofen Oral Suspension for Spasticity in Multiple Sclerosis

On February 7, the FDA approved Azurity Pharmaceuticals’ baclofen oral suspension Concentrated Formulation, in doses of 25 mg per 5 mL (5 mg/mL) for the treatment of spasticity in patients with multiple sclerosis. Is intended to provide relief of flexor spasms and concomitant pain, clonus, and muscle rigidity, the new liquid formulations offers an additional benefit for patients who have trouble swallowing pills.1

Available as a generic medication in the US since 1977, the new formulation is expected to be used to also treat patients with spinal cord injuries and other spinal cord diseases. The medication is not indicated for the treatment of skeletal muscle spasms resulting from rheumatic disorders.

Amit Patel, chairman and chief executive officer of Azurity Pharmaceuticals, said in a statement at the time that “the approval of Fleqsuvy represents our commitment to providing innovative alternative formulations that address individualized patient needs. The clinical profile of Fleqsuvy allows for a tailored and flexible approach to dosing for patients suffering from spasticity, a debilitating symptom that may impact daily functioning.”

FDA Approves Baclofen Oral Suspension for Spasticity in Multiple Sclerosis

Pimavanserin sNDA Resubmitted for Dementia-Related Psychosis

In late February, Acadia Pharmaceuticals resubmitted their supplemental new drug application (sNDA) to the FDA for pimavanserin (Nuplazid) to treat hallucinations and delusions associated with dementia-related psychosis (DRP).2 Pimavanserin, a selective serotonin inverse agonist and antagonist preferentially targeting 5HT2A receptors, had its sNDA originally accepted in July 2020, but months later, in July 2021, the FDA issued a complete response letter (CRL), stating it could not approve the drug in its present form.3

The agency cited a lack of statistical significance in some of the subgroups of dementia and insufficient numbers of patients with certain less common dementia subtypes. The single-center phase 2 Study -019, a supportive study in the sNDA filing, was considered not adequate and well-controlled in the original CRL. The resubmission included additional analyses from that study as well as the pivotal phase 3 HARMONY study (NCT03325556). In HARMONY, pimavanserin met its primary end point, significantly reducing the risk of relapse of psychosis by 2.8-fold compared with placebo (HR, 0.353; one-sided P = .0023).4 The double-blinded, placebo-controlled trial included 392 patients with various dementia subtypes, including Alzheimer disease, Parkinson disease (PD) dementia, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.

Pimavanserin has been FDA-approved for the treatment of hallucinations and delusions associated with PD psychosis since 2016. It remains one of the only few FDA-approved medications to treat patients with this condition.5

Pimavanserin sNDA Resubmitted for Dementia-Related Psychosis

FDA Clears INDs for Gut-Derived Parkinson Disease Agents MRx0005 and MRx0029

Also in late February, the FDA accepted 4D Pharma’s investigational new drug application (IND) for their live biotherapeutic, gut-derived PD agents MRx0005 (Parabacteroides distasonis) and MRx0029 (Megasphaera massiliensis), with a first-in-human phase 1 study expected to begin mid-2022. The new phase 1 study will be a multicenter, randomized, double-blind study with an active placebo group to assess the safety and tolerability of the 2 investigational agents in separate cohorts of patients with PD.6

In preclinical studies, MRx0005 and MRx0029 were shown to reduce neuroinflammation and protect neurons from oxidative stress-induced death. Discovered using 4D Pharma’s MicroRx platform, the therapeutics have also demonstrated an ability to protect against the loss of dopamine metabolites and dopamine-producing neurons in the brain and in animal models of Parkinsonian syndrome.

"Parkinson disease is a devastating condition impacting more than 10 million people globally. As the global population ages, this number will continue to increase. There is growing evidence suggesting that the gut-brain axis could be key to developing new treatments for several neurological disorders, particularly Parkinson disease," Peter LeWitt, MD, Sastry Foundation Endowed Chair in Neurology, Wayne State University School of Medicine, and coordinating investigator of the phase 1 trial, said at the time of the announcement. "Oral, gut-targeted treatments such as 4D pharma’s Live Biotherapeutics MRx0005 and MRx0029 offer an exciting new way for possibly slowing Parkinson’s disease progression. The development of these potential new therapies is really breaking new ground in the field."

FDA Clears INDs for Gut-Derived Parkinson Disease Agents MRx0005 and MRx0029

Biogen Releases Statement in Response to High Prices of Aducanumab

In FDA-adjacent news, after its landmark FDA approval in June 2021, questions surrounded the cost and accessibility of aducanumab (Aduhelm; Biogen), the first FDA-approved medication for patients with Alzheimer disease (AD) since 2003. In mid-February 2022, Biogen issued a 31-page statement in response to the proposed national coverage determination from the Centers for Medicare & Medicaid Services (CMS), asserting that patients with AD should have immediate access to treatments that have been FDA-approved. They also noted that concerns raised by CMS pertaining to this class of treatments may be answered with more real-world use.7

The original proposal stated that the government’s health insurance program would only cover the administration of the medication for patients who are partaking in CMS-approved randomized control trials that satisfy its criteria, as well as those in trials supported by the National Institutes of Health. The proposed program, authored by a group that included Joseph Chin, MD, MS, deputy director, Coverage and Analysis Group, concluded that aducanumab has not confidently demonstrated a clinically meaningful improvement in health outcomes, nor has it established itself as a reasonable and necessary treatment under section 1862(a)(1)A) of the Social Security Act.8

“We remain steadfast in our commitment to patient choice and urge CMS to provide coverage for FDA approved treatments,” Maha Radhakrishnan, MD, chief medical officer, Biogen, said in a statement provided to NeurologyLive®. “Biogen is committed to generating data from real-world usage and with coverage, Alzheimer’s disease patients will be able seek treatment instead of being restricted to enrolling in randomized controlled trials where they may receive a placebo or be limited by other coverage criteria.”

Biogen Releases Statement in Response to High Prices of Aducanumab
1. Azurity Pharmaceuticals, Inc. announces FDA approval of Fleqsuvy (baclofen oral suspension). News release. Azurity Pharmaceuticals. February 7, 2022. Accessed March 23, 2022. https://www.biospace.com/article/releases/azurity-pharmaceuticals-inc-announces-fda-approval-of-fleqsuvy-baclofen-oral-suspension-/
2. Acadia Pharmaceuticals announces resubmission of supplemental new drug application to US FDA for Nuplazid (pimavanserin) to treat Alzheimer disease psychsosis. News release. Acadia Pharmaceuticals. February 16, 2022. Accessed March 23, 2022. https://ir.acadia-pharm.com/news-releases/news-release-details/acadia-pharmaceuticals-announces-resubmission-supplemental-new
3. Acadia Pharmaceuticals Receives Complete Response Letter from U.S. FDA for Supplemental New Drug Application for Pimavanserin for the Treatment of Hallucinations and Delusions Associated with Dementia-Related Psychosis. April 5, 2021. Accessed March 23, 2022. https://www.businesswire.com/news/home/20210405005229/en/Acadia-Pharmaceuticals-Receives-Complete-Response-Letter-from-U.S.-FDA-for-Supplemental-New-Drug-Application-for-Pimavanserin-for-the-Treatment-of-Hallucinations-and-Delusions-Associated-with-Dementia-Related-Psychosis
4. Foff EP, Devanand DP, Ballard C, McEvoy B, Stankovic S. HARMONY: response to Pimavanserin in the 12-week, open-label treatment phase. Presented virtually at AAIC 2020. Poster 4543
5. FDA approves first drug to treat hallucinations and delusions associated with Parkinson disease. FDA. April 26, 2016. Accessed March 23, 2022.https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-hallucinations-and-delusions-associated-parkinsons-disease
6. 4D Pharma announces FDA clearance of IND application for Live Biotherapeutics MRx0005 and MRx0029 for the treatment of Parkinson disease. News release. 4D Pharma. February 22, 2022. Accessed March 23, 2022. https://www.4dpharmaplc.com/en/newsroom/press-releases/fda-clearance-ind-mrx0005-and-mrx0029-parkinsons-disease
7. Re: Proposed decision memorandum for monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease (CAG-00460N). February 10, 2022. Accessed March 23, 2022. https://investors.biogen.com/static-files/48bc8500-bf36-4be1-ae87-81d4bab2d05f
8. Jensen TS, Chin J, Baldwin J, et al. Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer’s Disease. CMS website. January 11, 2022. Accessed March 23, 2022. https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=Y&ncaid=305&doctype=all&timeframe=30&sortBy=updated&bc=20
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