REMS and Its Potential Effect on Formulary Decisions

If a drug has a potential safety concern, the FDA may require the manufacturer to submit a Risk Evaluation and Mitigation Strategy (REMS).

By 2006, the US Food and Drug Administration (FDA) was under fire for approving medications without first compiling adequate safety information. As a result, Congress passed legislation to expand the agency’s authority to require additional data for certain drugs or biologics to ensure that a drug’s benefits outweigh the risks associated with taking the drug. If a drug has a potential safety concern, the FDA may require the manufacturer to submit a Risk Evaluation and Mitigation Strategy (REMS). Examples of REMS components include medication guides; patient package inserts; a communication plan for healthcare providers; and elements to ensure safe use, including requirements for those who prescribe, dispense, or use the drug.

The program went into effect in March 2008, and has already had an impact on more than 80 products, including some high-profile agents like natalizumab for multiple sclerosis, bosentan for pulmonary arterial hypertension, botulinum toxin A for cosmetic use, among others (the full list is available at http://www.fda.gov/ Drugs/DrugSafety/PostmarketDrug SafetyInformationforPatientsandProviders/ucm111350.htm). The REMS programs required for these medications vary from providing additional elements (ie, a patient package insert) to elements to assure safe use (or ETASU). Elements to assure safe use may be required for approved products when an assessment and edication guide, patient package insert, or communication plan are not sufficient to mitigate these risks. According to Dean Erhardt, MBA, Principal, D2 Pharm Consulting, “ETASU is a performance- linked access program for prescribers, infusion sites, pharmacies, patients, and/or other potential stakeholders that will have to enroll and/or be certified in order to prescribe, administer, or receive a certain product.” It may imply restricted access points for dispensing of the product as well, resulting in a limited number of specialty pharmacies through which it is available. This would entail special training in prescribing and dispensing the agent.

Ed Pezalla, MD, National Medical Director, Aetna, and President of The Pharmacy & Therapeutics Society, asked perhaps the most important question: “How will we address medications that have required monitoring [REMS] programs?” In other words, how will a REMS program impact formulary decision making?

Raulo S. Frear, PharmD, Director, Pharmacy Services, The Regence Group, wondered if agents with associated REMS programs might infer greater safety, and be made preferred products, because of their increased scrutiny. Otherwise, it is possible that formulary decision makers may shy away from these products, especially if they have complex REMS requirements. “In the case of pain-relief products,” he said, “will clinicians go back to using older pain-relieving agents, which have their own safety disadvantages?”

“If a product doesn’t have a REMS requirement,” Mr. Erhardt commented, “it may be placed on a lower formulary tier, just because it is less complicated to utilize.” Finally, the disturbing fact is that when a brand name product with a REMS program requirement goes off patent, any generic introduced to the market will also require that REMS program, according to Mr. Erhardt. This could have the effect of narrowing the difference in pricing between generic and branded agents, which is not good news for managed care organizations.

The trade-off may be safer products, but with higher prices.

Sources: Erhardt DP: Risk Evaluation Mitigation Strategy (REMS) initiatives; Pezalla EJ: President’s address; Frear RS: What’s in the Pipeline? Presented at the ninth annual conference of The Pharmacy & Therapeutics Society, National Harbor, MD, November 5-6, 2009.

Originally printed in Managed Market Media, December 2009, Vol. 1, No. 9.