Preventing Abuse of REMS and Other Techniques Used to Boost Profits of Revlimid

Additional legislation and regulation are needed to prevent abuse of Risk Evaluation and Mitigation Strategy (REMS) programs and other techniques used to stop generic drugs from entering the US market, according to authors of an article published in JCO Oncology Practice.¹

The article details how Celgene and Bristol Myers Squibb used the REMS program RevAssist and other measures to keep generic versions of Revlimid (lenalidomide) off the market so they could continually raise the drug’s price.

Though some recent legislation may prevent some of this abuse in the future, additional reform is needed, according to study author Charles L. Bennett, MD, PhD, of the University of South Carolina in Columbia, and colleagues.

Revlimid’s Price Hikes

Dr Bennett and colleagues noted that the price of Revlimid was raised 22 times in the US between 2005 and 2020. The cost of a 1-month supply rose from $4515 to $16,023 during that time. By 2020, Revlimid was the third largest revenue-earning pharmaceutical drug worldwide.

Celgene cited research and development costs as the primary drivers of these price hikes. However, a 2019-2021 investigation by the House of Representatives Committee on Oversight and Reform showed that price increases were actually used to boost net sales and improve earnings.

Research and development for Revlimid has primarily been federally funded. More than half of the trials Celgene reported as necessitating price increases from 2016 to 2018 were not funded by the company.

Other factors, such as product, marketing, and manufacturing costs, did not necessitate price increases for Revlimid either.

In fact, Celgene rewarded executives with bonuses for price increases of Revlimid. During a period of substantial price increases between 2006 and 2017, for example, top executives received a total of $400 million in compensation.

Keeping Generics Off the Market

Celgene was able to continue raising the price of Revlimid because the company effectively kept generic versions of the drug off the market.

House investigators uncovered Celgene memos directly stating the company’s use of RevAssist to prevent generic competition. Celgene filed 22 patents for RevAssist and 27 patents for Revlimid.

The patents made it easier for Celgene to sue generic competitors for patent infringement. Brand name manufacturers can delay generic approvals for 30 months by suing generic manufacturers for patent infringement, even if a court ultimately does not agree that the competitor is guilty.²

Celgene also prevented generic drug competitors from obtaining samples to prove that their product is bioequivalent to Revlimid.¹ The US Food and Drug Administration (FDA) estimated that Celgene used RevAssist to prevent 14 generic competitors from obtaining samples.

Generic competitors of Revlimid did enter the market in 2022, but this was done under reverse payment patent settlements, which limited generic production until 2026. These settlements, also known as pay-for-delay agreements, allow brand name companies to pay generic manufacturers to delay the entrance of drugs into the market.³

Preventing Abuse

Dr Bennett and colleagues noted that regulation and legislation could prevent the types of abuse that led to Revlimid becoming the third largest revenue-earning pharmaceutical drug worldwide.

For example, the FDA could collaborate with the Patent and Trademark Office “to determine whether individual REMS patents claim a method for using a drug,” and this could eliminate unjustified delays in reviews of generic drug applications.

A bill that was introduced in the Senate last month, the Preserving Access to Affordable Generics and Biosimilar Act, would limit the use of reverse payment agreements.⁴ The bill would allow the Federal Trade Commission to “initiate proceedings against parties to any agreement resolving or settling a patent infringement claim in connection with the sale of a drug or biological product.”

Such agreements would violate the bill if the filer of a generic drug or biosimilar application received anything of value in exchange for agreeing “to limit or forego research, development, manufacturing, marketing, or sales of the generic drug or biosimilar.”

Another bill that was introduced in the Senate last year, the Fair Accountability and Innovative Research Drug Pricing Act, would require “manufacturers to report about certain price increases for prescription drugs and biological products with a wholesale cost of at least $100 per month.”⁵

The CREATES Act, which was passed in 2019 as part of the Further Consolidated Appropriations Act of 2020, already addresses the issue of manufacturers using REMS to prevent other companies from accessing samples of brand name drugs.⁶ Developers of generics and biosimilars can sue companies that refuse to sell them samples of brand name drugs needed to support their generic or biosimilar applications.

However, Dr Bennett and colleagues noted that CREATES “depends on time-consuming litigation and does not go far enough to prevent REMS-related strategic delays,” so “additional policy reforms to address strategic abuse of REMS in particular are needed.”¹

Disclosures: Some authors of the JCO Oncology Practice article declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.