The U.S. Food and Drug Administration (FDA) is in charge of approving medications, ensuring that they are safe and effective. Since 2010, there have been more approvals for specialty drugs than traditional drugs,1 and 79% of specialty drugs approved in 2023 have limited distribution pharmacy requirements2, meaning they can only be dispensed by certain specialty pharmacies.
In 1992, the FDA began its Accelerated Approval Program, a program reserved for medications that both “treat serious conditions” and “fill an unmet medical need based on a surrogate endpoint.” This surrogate endpoint—a measurement such as a biomarker or cognitive score—is used to predict the clinical benefit of the drug, and is what allows the FDA to grant early approval.
Despite the program being around for decades, more accelerated approvals are occurring now than ever—nearly 50% of all accelerated approvals have been submitted since 2016.3 Even gene therapies, such as Elevidys for Duchenne muscular dystrophy, are receiving accelerated approval. Nonetheless, many drug studies accepted into the accelerated path are ongoing and many are behind schedule. As pharmacy benefit managers (PBMs) develop formularies, it is especially important that they rely on a clinical-first approach in this rapidly changing environment.
As the number of accelerated approvals has grown dramatically, there have been some concerns about potential bias in the process. In 2021, the FDA granted accelerated approval to Aduhelm, a drug intended to treat Alzheimer’s disease despite being rejected by an FDA advisory committee over safety and efficacy concerns. A congressional report found that the approval process had been “rife with irregularities” and showed “lapses in protocol.”
These findings have led to public scrutiny of the Accelerated Approval Program and drugs that appear to be approved with surrogate clinical data. Accelerated approvals are required to complete confirmatory trials, however a study conducted by the Office of Inspector General found that out of 278 accelerated approvals since 1992, 104 have incomplete confirmatory trials. Despite this incomplete data, approximately 80% of confirmed accelerated approvals were ultimately granted full approval.4
These newly surfaced reservations surrounding accelerated approvals underscore how critical it is for PBMs to thoroughly evaluate the clinical soundness of drugs when developing formularies.
Taking into consideration the concerns surrounding the Accelerated Approval Program, maintaining a strong relationship with a good PBM is important to ensure a clinical-first approach. When it comes to developing formularies for both specialty and traditional drugs, a highly competent PBM has the following priorities in mind:
- Clinical appropriateness over cost – Any potential savings or rebates will always come second to ensuring that patients have access to the best, most appropriate therapy for their disease state.
- Robust coverage – The formulary should cover most conditions and also offer a formulary exceptions process whereby even non-preferred drugs can be covered if and when clinically appropriate.
- Independent evaluations – Formularies will be based on the evaluations of independent physicians, guaranteeing that the clinical efficacy of a drug takes precedence.
The PBM will also stay up-to-date with the drug pipeline, to ensure that it is prepared to move quickly in the best interests of clients and patients. It will track all drugs that are in early clinical development and proactively design formularies and programs based on upcoming approvals. A good, thorough development process with distinct checkpoints at each step will ensure that every possible angle is explored in pursuit of a clinical-first formulary.
When building a formulary, Express Scripts relies on the expertise of three distinct committees:
- Therapeutic Assessment Committee – Pharmacists and physicians review specific medications following FDA approval using medical literature and published clinical trial data.
- National Pharmacy & Therapeutics Committee – Independent, actively practicing physicians and pharmacists who represent a broad range of specialty practice areas and render decisions on formulary placement. This committee does not have access to any information regarding Express Scripts' rebates or negotiated discounts, and does not use price to make formulary placement decisions in any way.
- Value Assessment Committee – Employees from formulary, product, finance, human resources and clinical account teams who consider drug values by evaluating the net cost, market share and utilization trends of clinically similar medications.
With the breadth of independent, expert knowledge constituted by these committees, Express Scripts is able to look out for both patients and payers when faced with the limited amount of data behind certain accelerated approvals. Ultimately, affordable access to a high-quality pharmacy benefit depends on clinically-sound strategies that keep the patient and their safety top-of-mind.
1 Compilation of CDER New Molecular Entity (NME) Drug and New Biologic Approvals.
2 ESI Office of Clinical Evaluation Drug Approvals through August 2023.
3 Compilation of CDER Drug and Biologic Accelerated Approvals through December 31, 2021.
4 Compilation of CDER Drug and Biologic Accelerated Approvals through June 30, 2022.