FDA Drug Approvals, Neurology — 2021 Midyear Review

August 20, 2021

Ponvory (ponesimod)

Ponesimod] is a sphingosine 1-phosphate (S1P) receptor 1 modulator that binds with high affinity to S1P receptor 1 and blocks the capacity of lymphocytes to regress from lymph nodes, reducing number of lymphocytes in peripheral blood. Ponesimod is indicated for relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

Approval for ponesimod was based on a head-to-head phase 3 trial (n = 1133). In that trial, ponesimod demonstrated superior efficacy in significantly reducing annual relapse by 30.5% compared with teriflunomide in patients with relapsing MS. Over the study period, 71% of patients treated with ponesimod had no confirmed relapses, compared with 61% in the teriflunomide group. JAMA Neurol. 2021 May 1;78(5):558-567

Amondys 45 (casimersen)

Casimersen is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass. PMO binds to exon 45 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Casimersen is indicated for Duchenne muscular dystrophy in patients with a confirmed mutation amenable to exon 45 skipping.

The ESSENCE trial—a placebo-controlled confirmatory trial to support the casimersen approval—is ongoing and expected to conclude in 2024. In the study, patients who received casimersen showed a significantly greater increase in dystrophin protein levels from baseline to week 48 of treatment compared with those who received placebo. Study of SRP-4045 and SRP-4053 in DMD Patients (ESSENCE)

Aduhelm (aducanumab)

Aducanumab is a monoclonal antibody that targets beta-amyloid and binds to aggregated forms of beta-amyloid. The FDA granted accelerated approval for aducanumab based on the reduction in amyloid-beta plaques observed in patients treated for Alzheimer disease. The prescribing information specifies approval for patients with mild cognitive impairment or a mild dementia stage of disease, the population studied in the clinical trials. The prescribing information states that continued approval is contingent upon verification of clinical benefit in confirmatory trial(s).

Accelerated approval was based on 2 phase 3 trials. In a letter released by the FDA, the rationale for approval was explained. One of the clinical trials (EMERGE) was the first to show that high-dose aducanumab reduced amyloid-beta plaques—a hallmark finding in the brain of patients with Alzheimer disease—and slowed cognitive decline. The second trial (ENGAGE) showed no benefit of aducanumab versus placebo, at low or high doses. Debate continues regarding this approval. The materials for the FDA Peripheral and Central Nervous System Drugs Advisory Committee Meeting provide detailed analyses of these phase 3 trials.

Nulibry (fosdenopterin)

Fosdenopterin is indicated to reduce the risk of mortality in patients with molybdenum cofactor deficiency type A (MoCD-A), a rare disease. Fosdenopterin provides an exogenous source of cyclic pyranopterin monophosphate (cPMP). MoCD-A is caused by a mutation in the molybdenum cofactor synthesis 1 gene (MOCS1), which causes a deficiency in molybdenum cofactor production. The exogenous intermediate substrate cPMP provided by the drug is subsequently converted to molybdenum cofactor, which is required for the activation of essential enzymes (eg, sulfite oxidase) to reduce the levels of neurotoxic sulfites. Decreased sulfite oxidase activity is thought to cause the severe and rapidly progressive CNS damage observed in patients with MoCD-A.

Other neurology approvals

Gocovri (amantadine) - Gained FDA approval as adjunctive treatment to levodopa/carbidopa for Parkinson disease in patients experiencing "off" episodes.

Nurtec ODT (rimegepant) - Indication for migraine expanded to include preventive therapy. Originally approved for acute treatment.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.