Extrapolation of indications by the Food and Drug Administration (FDA) has been widely accepted by providers, payers, and most patient groups. Yet how to address the approval of a narrow indication list (or skinny label) seems less settled.
The four FDA-approved adalimumab biosimilars received the agency’s endorsement for a large set of Humira®’s 10 indications. Amjevita® and its brethren were approved for the treatment of moderate-to-severe rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, moderate-to-severe Crohn’s disease in adults, plaque psoriasis, moderate-to-severe polyarticular juvenile idiopathic arthritis, and moderate-to-severe ulcerative colitis. Missing are indications to treat pediatric Crohn’s disease, hidradenitis suppurativa, and noninfectious uveitis (regardless of severity). When payers are asked whether these missing indications (especially involving other autoimmune disorders) are important for coverage decision making, they will likely agree that it makes little difference to them.
In perhaps the more important biosimilar example, rituximab, the indications are split between cancer treatment (e.g., non-Hodgkin’s lymphoma and chronic lymphocytic leukemia) and autoimmune therapy (e.g., rheumatoid arthritis, polyangiitis, pemphigus vulgaris). Although the dosing rate (50 mg/hr) is the same, Rituxan is given as part of a cytotoxic chemotherapy regimen for patients with non-Hodgkin’s cancer versus methotrexate and methylprednisone for autoimmune treatment. The two rituximab biosimilars (Truxima® and Ruxience®) approved by the FDA do not have the rheumatoid arthritis indication, although Ruxience has received approval for polyangiitis.
The reasons their manufacturers sought the skinny labels could be many, including avoidance of patent infringement, quicker path to FDA approval, or simply limited resources. However, Pfizer did complete a phase 3 trial in RA for Ruxience. Currently, Amgen/Allergan have completed phase 3 trials for both non-Hodgkin’s lymphoma and rheumatoid arthritis for their investigational biosimilar ABP 798. It is possible that the partners could submit a 351(k) biologic license application at the end of Q4 2019 or Q1 2020.
For payers, the presence of skinny labels for biosimilars versus approval for the entire set of indications matters little. In several market research projects we have conducted with managed care medical directors and pharmacy directors, their answers have been consistent: If the biosimilar is approved by the FDA and is covered by the health plan or insurer, then the payer will be far less concerned how the biosimilar is used. The reasons are simple: Payers are gaining comfort with biosimilar use. If the reference product and biosimilar have been demonstrated to be sufficiently equivalent to produce equivalent outcomes, and the biosimilar is less expensive, why overmanage its use?
Further support for this view was published this month in BioDrugs. These South Korean authors evaluated 11 head-to-head randomized, control trials of rituximab biosimilars for use either non-Hodgkins lymphoma or RA. A total of 3,163 patients were included in the meta-analysis. Response rates in the trials for lymphoma and RA were consistently equivalent, and no significant differences were revealed in the formation of antidrug antibodies. Perhaps the best opportunity for managed care organizations to restrict the use of a biosimilar (or biologic) outside of step therapy is the ubiquitous prior authorization (PA). Today, there is little, if no, reason for PA criteria to be different for a reference biologic or its biosimilar(s), other than price preference. In that case, the skinny label has little effect on a payer’s coverage.