Evaluation of REMS Approved and Released by the FDA

A study analyzing drug approvals and risk evaluation and mitigation strategies (REMS) approvals suggests that most therapies with REMS are indicated for large patient populations and are approved using standard, rather than accelerated, pathways.

Despite specialty therapies’ association with serious side effects and stringent adherence requirements, a new study suggests that many of the risk evaluation and mitigation strategies (REMS) approved since 2008 pertain to traditional pharmaceutical products.

“Traditionally, pharmaceutical products with serious potential risks were associated with products in niche therapeutic areas with small patient populations and without appropriate therapeutic alternatives,” the researchers wrote. “This study found that most products with REMS were in therapeutic classes with large patient populations and only a small percentage of them had orphan drug designation.”

The study, published in the January/February 2014 edition of Research in Social and Administrative Pharmacy, analyzed trends in REMS approved between 2008 and early 2012.

Researchers collected drug approval data from the FDA Approved Drug Products with Therapeutic Equivalence Evaluations, the Drugs@FDA database, and the list of Approved Risk Evaluation and Mitigation Strategies list from January 2008 to May 2012. They recorded the application type, including whether it was a new drug application (NDA), biologic licensing application (BLA), or abbreviated new drug application (ANDA); the marketing application number; and the marketing application approval date.

In addition, researchers noted whether applications were granted priority review or orphan drug designation or whether the product was discontinued during the study period.

From January 2008 through May 31, 2012, the FDA approved Risk Evaluation and Mitigation Strategies for 259 total products, which included 217 NDAs, 32 BLAs, and 10 ANDAs. The approvals covered 138 chemical entities and 32 biologic products, the researchers reported.

Therapies to treat central nervous system conditions had the highest number of REMS, with 54 products (31.8% of the total products with REMS) having approved REMS. Antineoplastic and immunomodulating agents had the second-highest number of REMS, with 26 products (15.3%) having approved REMS. Digestive tract and metabolic therapies had the third-highest number of REMS, with 20 products (11.8%) having REMS indications.

The study did not cover treatment areas, so the therapeutic categories could include both specialty and nonspecialty products.

During the study period, 18 products received orphan drug designation, which included 12 chemical entities and 6 biologic products. The FDA assigned priority review status to 53 active ingredients as well. The priority review ingredients did not include any biologic entities, however.

Although biologic entities did not receive priority review status during the study period, the FDA approved 88 biologic therapies by May 31, 2012. Of those products, 30 required REMS.

A higher percentage of REMS for BLAs tended to be approved on the same day as the first marketing application approval than for NDAs, with just under half of the REMS for BLAs being approved on the same day as the marketing approval, the researchers added.

The researchers also analyzed the average time between the drug’s approval date and the approval of REMS, which tended to be approximately 14 years. In addition, the time between marketing approval and REMS approval tended to be longer for traditional chemical entities than for biologic products.

The most commonly prescribed REMS elements included medication guides, which were included in 94.1% of all REMS. Communication plans were used in 31.8% of REMS, elements to assure safe use appeared in 18.2% of REMS, and implementation systems appeared in 14.7% of REMS. When accounting for a 2011 revision to REMS policies that exempted 94 products from having REMS, medication guides remained the most frequently seen REMS element, and were present in 88.16% of the remaining REMS.

“The FDA’s role concerning the safety of pharmaceuticals approved for marketing in the US is evolving,” the authors wrote. “REMS were initially considered one of the most prominent strategies for managing drug safety risks; most recent FDA policy changes indicated that REMS will be reserved for a small number of high-risk medications.”