Does Orphan Drug Status for Rofecoxib Open the Door for Increased Use?

Medicare Set-Aside Blog, Rx/Pharmacy on December 13, 2019
Posted by Leah King, PharmD, JD, Independent Pharmacy Consultant

Just over two years ago, the FDA granted orphan drug status to rofecoxib for the treatment of hemophilic arthropathy. Rofecoxib was previously marketed by Merck under the trade name of Vioxx and depending on your age, you may recall hearing about Vioxx in the news. Vioxx was initially approved by the FDA in 1999 for the treatment of various painful conditions including osteoarthritis and rheumatoid arthritis. Vioxx was the second drug in a new class of medications known as cyclooxygenase-2 (COX-2) inhibitors. From a pharmacological perspective, COX-2 inhibitors are similar to non-steroidal anti-inflammatory drugs (NSAIDs) but have one important distinction. NSAIDs exert their action by inhibiting two enzymes, cyclooxygenase-1 (COX-1) and COX-2. Drugs like Vioxx selectively target the COX-2 enzyme but not the COX-1 enzyme and as a result, patients experience fewer of the side effects that are traditionally associated with NSAIDs. One of the most problematic side effects of NSAIDs is gastrointestinal irritation and ulceration, which is mediated by the inhibition of COX-1. By avoiding COX-1, drugs like Vioxx were seemingly a perfect solution for those patients who couldn’t tolerate traditional NSAIDs due to a history of gastrointestinal irritation, bleeding or ulceration. Other COX-2 inhibitors include Celebrex (FDA approved in 1998) and Bextra (FDA approved in 2001).

Merck voluntarily withdrew Vioxx from the market in 2004, following reports of significantly increased risk of cardiovascular events such as heart attack and stroke associated with long-term use. In 2005, the FDA pulled Bextra from the market due to similar concerns. Celebrex was allowed to remain on the market; however, the FDA required Pfizer to include a stronger warning in the product’s label regarding an increased risk of heart attack and stroke.[1] Since 2005, Celebrex has enjoyed a strong market position as the only commercially available COX-2 inhibitor. Celebrex has been the subject of many of our blogs over the past year or so, and those of us in the workers’ compensation arena know it well and have followed it closely.  

Arthropathy is a type of joint disease that’s common in patients with hemophilia due to chronic bleeding into the joint space, a condition called hemarthrosis. These episodes of hemarthrosis lead to low-grade inflammation of the joint and eventually, destruction of the joint tissues.[2] There are no FDA approved treatments for hemophilic arthropathy. Due to the underlying condition of hemophilia, traditional NSAIDs must be avoided since NSAIDs inhibit platelet aggregation and increase the risk of bleeding. Due to the sheer lack of alternative medications, opioids have been the mainstay of therapy for these patients. As a result of the opioid crisis, there have been a number of targeted efforts designed to educate prescribers about the importance of avoiding opioids whenever it is clinically feasible to do so. Just a few months ago in October, the Department of Health and Human Services published a guide for clinicians concerning the appropriate dosage reduction or discontinuation of opioid therapies. Stay tuned to our blog for an upcoming article with more details on those guidelines.

Orphan drug designation is available via a regulatory mechanism that allows drugs and biologicals to be endorsed as a treatment for rare diseases. It is important to remember that orphan drug designation is not the same as full FDA approval so in the current status, rofecoxib remains non-FDA approved and non-Medicare covered. That being said, it would not be a complete surprise to see a resurgence of rofecoxib for other painful conditions. Due to the heightened focus on identifying alternatives to opioids, NSAIDs and COX-2 inhibitors are more clinically appealing options as compared to opioids. In addition, the company that sponsored rofecoxib as orphan drug therapy for hemophilic arthropathy is a company called Tremeau Pharmaceuticals. The self-proclaimed strategy of Tremeau Pharmaceuticals is to develop and deliver non-opioid pain therapies for people with rare diseases and other conditions.[3] For those of us who were around when Vioxx was withdrawn from the market, it may seem surreal that we’re talking about rofecoxib again. This is proof that the world of pharmaceuticals is an ever-changing one, and it doesn’t stand still for very long. Since the decision to use a particular medication always comes down to an analysis of risks and benefits and new risks are always emerging, the result of any given analysis is subject to change. We will continue to monitor the status of rofecoxib and keep our readers apprised of any noteworthy developments.


[1] https://www.webmd.com/arthritis/news/20050407/bextra-taken-off-market-celebrex-gets-warning#1

[2] https://ortho-institute.org/care/hemophilia-treatment-center/hemophilic-arthropathy

[3] https://www.tremeaurx.com/our-strategy