Considerations in the development of generic disease therapies for multiple sclerosis

Abstract

Purpose of review: Medication prices are a major contributor to the high cost of care for multiple sclerosis (MS). The patents for some of the initial injectable therapies for relapsing MS recently expired, permitting development, regulatory approval, and marketing of generic alternatives with the potential for lower prices and cost savings to payers and patients.

Recent findings: A generic version of glatiramer acetate 20 mg administered by daily subcutaneous injection recently received regulatory approval in the United States. Two additional generic versions of glatiramer acetate have been submitted for regulatory review. The development and testing of generic disease-modifying therapies for MS such as glatiramer acetate, which are complex molecules, present several complicating factors.

Summary: This article provides background on the development of generics and reviews the status of generic glatiramer acetate.

Figure 1. Comparison of pivotal trials of innovator and generic MS disease therapies

(A) Pivotal trials of innovator drugs seek to show superiority on a clinical endpoint compared to placebo or an active comparator. (B) In contrast, pivotal trials of generic drugs seek to show equivalence of the generic and innovator on a more sensitive imaging endpoint.

Figure 2. Potential results of trials seeking to demonstrate equivalence

^a The upper and lower equivalence limits are negotiated with regulatory agencies. ^b,c The point estimates and 95% confidence internal (CI) fall within the equivalence limits, representing a positive equivalence trial. ^d Although the point estimate is the same as in (b), the 95% CI is not within the equivalence limits, representing a negative equivalence trial. ^e,f The results represent negative equivalence trials. Gd+ = gadolinium-enhancing.