Sustaining competition for biosimilars on the pharmacy benefit: Use it or lose it.

Congress passed the Biologic Price Competition and Innovation Act of 2009, specifically to offer market competition as a counterweight to the rising costs of biologic medicines. As of April 15, 2024, 49 biosimilars have been approved by the US Food and Drug Administration in 15 biologic categories. Biosimilar competition has been undeniably successful: Through 2022, biosimilars have saved the US health system $23.6 billion, without significant care disruption or reduced quality. Through 2023, adalimumab biosimilar competition has added an additional $6.5 billion to this total, primarily through greater rebates from the reference manufacturer. Despite launching at discounts as great as 85%, adalimumab biosimilars have not been given preferred formulary positioning in the vast majority of cases and have thus gained only 3% of market share through 2023, largely because of payers' and pharmacy benefit managers' preference for rebates over discounts. This situation may negatively influence future biosimilar development, posing a threat to a biosimilar pipeline that represents hundreds of billions in savings over the next 10 years.

Biosimilars in the USA: Will New Efforts to Spur Approvals and Access Spur Uptake and Cost Savings?

Unlike in Europe, US healthcare systems and payers are still awaiting significant savings related to biosimilar utilization. Costs related to biologic use continue to rise at double-digit rates, and biosimilars are seen as a major tool to control costs and increase access to biologic drugs. However, one 2018 report indicated that US$3.2 billion (only 3%) of biologic spending is subject to competition from biosimilar products. Although the European Medicines Agency did a great deal of pioneering work in biosimilar regulation, the US Food and Drug Administration is moving at approximately the same pace as the European Medicines Agency, based on the number of approvals at the same time after implementation of its regulatory pathway. Several unique factors in the USA have conspired to limit biosimilar access (e.g. delayed regulatory policies, extended patent litigation activities, federal reimbursement policies, the widespread use of rebate contracting, and limited competition). The US Federal Government is taking the initiative in an attempt to address these factors, and speed both biosimilar development and patient access. To date, the most significant cost savings in the US system associated with the introduction of biosimilars may be their ability to halt price increases of the reference product. The complexity of the healthcare delivery system, and how it is financed, will remain challenging to payers, manufacturers, health providers and patients as they seek ways to manage health expenditure growth.

Will the PCSK9 Inhibitors Be Employers' "Line in the Sand"?

After the introductions of sofosbuvir (Sovaldi) and ledipasvir plus sofosbuvir (Harvoni) for the treatment of hepatitis C, employers have become very sensitive to new, and especially unforeseen, factors that significantly raise healthcare costs. With the recent launch of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, self-insured and fully insured employers have been seeking information on this drug class and its potential for off-label use, which could amount to up to $23 billion in healthcare expenditures, according to a report from Prime Therapeutics. Based on their approved indications, 0.4% of commercial members may be eligible to use PCSK9 inhibitors, at a cost of $3.29 per member per month. Corporate employers are evaluating their options to manage the new expense associated with the novel PCSK9 inhibitors.

Payer Perspectives on PCSK9 Inhibitors: A Conversation with Stephen Gorshow, MD, and James T. Kenney, RPh, MBA.

The new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can have significant budget effects, depending on the breadth of the US Food and Drug Administration (FDA)'s approved labeling. American Health & Drug Benefits asked Stephen Gorshow, MD, Regional Medical Director, UnitedHealthcare, and James T. Kenney, RPh, MBA, Manager, Specialty and Pharmacy Contracts, Harvard Pilgrim Health Care, to participate in a teleconference to better understand how payers are approaching the management of these agents.

Is a Biologic Produced 15 Years Ago a Biosimilar of Itself Today?

Much of the testing required for the regulatory approval of a biosimilar is focused on proving that the new drug is sufficiently similar to the reference biologic in structure, pharmacokinetics or pharmacodynamics, clinical efficacy, and safety. However, the reference drug may itself have gone through some changes in the years since its approval, including those caused by alterations in the manufacturing process. Do these changes increase the risk that the reference drug may cause unexpected outcomes? It is up to the US Food and Drug Administration to decide whether the changes merit the need for additional studies to confirm that the drug meets the structural or clinical outcomes standard for the reference agent. Although it is extremely rare, a change in the production of one biologic drug (ie, epoetin alfa) did result in unanticipated serious immunologic side effects.

Reviewing the Unmet Needs of Patients with Multiple Sclerosis.

Significant innovations in the treatment of patients with multiple sclerosis (MS) have primarily addressed the frequency of flare-ups in relapsing-remitting MS (RRMS). Many advances have been made in this area, and the medical community may be on the verge of a serious discussion of what constitutes a truly effective MS treatment. Certainly, it is important to further delay MS flare-ups and more effectively treat RRMS symptoms. However, great strides in reducing or preventing MS-related disability and providing neuroprotection have been elusive. Many unmet needs are still voiced by patients with MS, clinicians, and caregivers. Current information on the need for progress in various areas is reviewed in this article, including psychosocial care, treatments for progressive MS, biomarker identification, functional outcome measures, individualization of treatment, reducing side effects of medications, and improving medication adherence.

The Latest Innovations in the Drug Pipeline for Multiple Sclerosis.

Several new medications are being investigated in late-phase studies for the treatment of patients with relapsing or progressive multiple sclerosis (MS). These agents represent a variety of mechanisms of action and provide not only lower relapse rates but also improvement in disabilities. The majority of investigational trials involve selective sphingosine-1-phosphate receptor 1 immunomodulators, such as laquinimod, ozanimod, ponesimod, and siponimod, in an effort to build on the success of fingolimod. Ocrelizumab is a CD20-positive B-cell-targeting monoclonal antibody with a promising new mechanism of action. Ofatumumab is also a CD20 inhibitor. Daclizumab, an interleukin-2 inhibitor, has evidence of good efficacy but is associated with unfavorable side effects. Masitinib is a mast-cell inhibitor that also has shown efficacy in Alzheimer's disease and amyotrophic lateral sclerosis. Phase 3 trials for some of these agents will conclude in the next 12 months, and their manufacturers are expected to apply for US Food and Drug Administration approval soon thereafter. This review article summarizes data for newly approved and late-phase investigational agents for the treatment of patients with MS.