Data from a pair of phase 3 studies suggest that the recently approved celecoxib oral solution (Elyxyb; Dr. Reddy’s Laboratories) offers safe and effective acute treatment of episodic migraine.
Sagar Munjal, MD
New phase 3 data suggest that celecoxib oral solution (Elyxyb), also known as DFN-15, may be an effective alternative to oral triptans in the acute treatment of episodic migraine.1
In a dataset of more than 1000 patients from 2 studies with more than 1200 participants (Study 1: n = 631 [80.5% retention; n = 508]; Study 2: n = 622 [80.1% retention; n = 498]), patients treated with the Dr. Reddy’s Laboratories’ agent reported higher rates of pain freedom and freedom from their most bothersome symptom, both after 2 hours. The data were presented at the American Headache Society (AHS) virtual annual scientific meeting on June 13, 2020.
The nonsteroidal anti-inflammatory drug (NSAID) was approved by the FDA for the treatment of acute migraine in adults with or without aura in May 2020, notably with a boxed warning related to a risk of serious cardiovascular and gastrointestinal (GI) adverse events (AEs).2,3 The selective COX-2 inhibitor was originally approved in capsule form as Celebrex (Pfizer) in 1998 and was indicated for the treatment of acute pain in patients with ankylosing spondylitis, osteoarthritis, primary dysmenorrhea, and rheumatoid arthritis.
“As is known, NSAIDs inhibit prostaglandin synthesis by blocking 2 cyclooxygenase isoforms, COX-1 and COX-2,” said presenting author Sagar Munjal, MD, vice president, clinical development and medical affairs, Dr. Reddy’s Inc. “There has been a lot of evidence that NSAIDs are effective in the treatment of episodic migraine, however, for celecoxib—a COX-2 inhibitor—the evidence is very minimal. Hence, the objective of this study.”
In Study 1, the celecoxib group (n = 272) reported pain freedom at 2 hours post-dose at a rate of 32.8% compared to 23.5% for the placebo group (n = 268; P = 0.2). Similarly, in Study 2, 35.6% of the celecoxib group (n = 283) reported pain freedom compared to 21.7% of the placebo group (n = 280; P <.001). Freedom from the patient-identified most bothersome symptom—between nausea photophobia and phonophobia—was observed in a higher proportion of celecoxib-treated (Study 1: 58.1%; Study 2: 57.8%) compared with placebo (Study 1: 43.9% [P = .003]; Study 2: 44.8% [P = .007]) as well.
Notably, a single study site in Study 1 observed a 75% placebo response in the first double-blind period; thus, as a statistically significant outlier, data from this site were excluded from the analysis.
“Once the statistically and clinically significant outlier site was removed, numerically, the difference was approximately similar between the [celecoxib] and placebo arms. However, statistical significance was achieved,” Munjal explained. When exploring the data with this outlier site, both pain freedom at 2 hours (celecoxib: 32.9%; placebo 25.8%; P = .075) and most bothersome symptom-freedom (celecoxib: 58.9%; placebo 45%; P = .003) favored the Dr. Reddy’s agent.
Trends with regard to pain relief after 2 hours were also observed in favor of celecoxib. In Study 1 and Study 2, respectively, 67.9% and 74.5% of the celecoxib groups compared to 55.3% (P = .004) and 60.5% (P <.001) with placebo. Additionally, sustained 2- to 24-hour pain freedom was better with celecoxib (Study 1: 28.9%; Study 2: 28.7%) compared with placebo (Study 1: 19.9% [P = .041]; Study 2: 18.1% [P <.009]).
The safety data was positive as well, with rates of treatment-emergent adverse event (AE) rates below 14% for both studies and all treatment periods. There were no serious treatment-emergent AEs or deaths were reported. Munjal and colleagues wrote that there were also no “remarkable findings” on laboratory tests, vital signs, or in any other safety assessments.
In the 2 multicenter, randomized, double-blind, placebo-controlled pivotal efficacy and safety studies, subjects were instructed to dose at moderate to severe headache pain. They were re-randomized into a second double-blind period (data of which is on file).
This oral solution’s boxed warning notes that NSAIDs can increase the risk of serious cardiovascular thrombotic events, such as myocardial infarction and stroke, thus Elyxyb is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Additionally, the label warns of possible spontaneous bleeding, ulceration, and perforation of the stomach or intestines, and that the elderly and those with prior history of peptic ulcer disease and/or GI bleeding are at higher risk.3 Data suggest that compared with naproxen and ibuprofen, among those with patients with osteoarthritis and rheumatoid arthritis, celecoxib is associated with a significantly lower risk of gastrointestinal events and significantly lower risk of renal events.2
For more coverage of AHS 2020, click here.
1. Lipton RB, Munjal S, Serrano D, Ianconangelo C, Tepper SJ, Dodick DW. DFN-15 (Celecoxib Oral Solution, 25 Mg/ml) in the Acute Treatment of Episodic Migraine: Efficacy Results from Two Phase III Randomized, Double-blind, Placebo-controlled Studies. Headache. 2020;60(S1 suppl). 1-156. doi: 10.1111/head.13854
2. BRIEF-FDA Approves Dr. Reddy's Laboratories' Elyxyb Oral Solution For Acute Treatment Of Migraine With Or Without Aura In Adults. Reuters. Published online May 5, 2020. Accessed May 5, 2020. reuters.com/article/brief-fda-approves-dr-reddys-laboratorie/brief-fda-approves-dr-reddys-laboratories-elyxyb-oral-solution-for-acute-treatment-of-migraine-with-or-without-aura-in-adults-idUSFWN2CN10I
3. Elyxyb. FDA Label. FDA website. Updated May 2020. Accessed May 5, 2020. accessdata.fda.gov/drugsatfda_docs/label/2020/212157s000lbl.pdf