Drug Review Profiles

Pink Sheet Drug Review Profile looks at how the agency determined that Amylyx’s ‘conceptual basis’ for use of the drug’s two active ingredients to treat ALS was enough to satisfy the combination drug rule; the sponsor also was allowed to submit certain animal studies and drug-drug interaction data during the course of the NDA review.

Agency considered Amylyx’s plan to submit unblinded efficacy data from the ongoing Phase III trial during the ALS drug's NDA review but ultimately decided against it, citing concerns about study integrity and the small amount of data likely to be available.

The post hoc comparison of an exploratory, long-term survival benefit in the CENTAUR trial to historical controls in two ALS patient databases lacked prespecification and a common treatment protocol, and potential differences in prognostic factors may have confounded the results.

European Medicines Agency insisted on a stricter statistical analysis than the US FDA for demonstrating equivalence on the primary endpoint for both Coherus/BioEq’s Cimerli and Samsung Bioepis’ Byooviz; there also were differences in the regulators' preferred primary analysis population and primary endpoint interval.

Information on mechanism of action, pharmacokinetics, immunogenicity and toxicity convinced the US FDA there was no risk in terms of safety or diminished efficacy of switching between Cimerli and the reference product, Genentech’s eye drug Lucentis.

A timeline of the development and approval of Moderna's mRNA vaccine, and a listing of FDA reviewers on the biologics license application.

Five of the six modeling scenarios in the FDA’s quantitative benefit-risk assessment on myocarditis with Moderna’s vaccine assumed Omicron as the dominant circulating strain, with assumed average vaccine effectiveness of only 30% against COVID-19 cases and 72% against hospitalizations.

Pink Sheet’s Drug Review Profile series looks at the unusual history of a systemic sclerosis interstitial lung disease indication for Genentech’s Actemra that was revived at the FDA’s behest and vetted by CDER’s high-level CDER policy council.

Detailed timeline of the development and review of Genentech’s Actemra (tocilizumab) in systemic sclerosis-associated interstitial lung disease

Janssen’s ponesimod for relapsing multiple sclerosis had a slightly faster review in the US.

In approving ponesimod for relapsing multiple sclerosis, neither the FDA nor EMA included in labeling data from a novel patient-reported outcomes fatigue instrument; FDA said the PRO was not shown to be capable of measuring within-patient change, while EMA said the difference relative to Sanofi’s Aubagio fell short of the threshold for a clinically meaningful benefit.

Janssen went against EMA’s advice on the choice of secondary endpoints for its multiple sclerosis drug Ponvory (ponesimod), but still enjoyed a relatively brisk review. The hierarchical order of endpoints did not seem to ruffle any feathers among US FDA reviewers.