Tremeau Receives May Proceed Notification From FDA For Phase III Program in Acute Migraine For TRM-201 (Rofecoxib)

• This is the second IND opened for a clinical program developing Tremeau’s lead asset, TRM-201 (rofecoxib)
• Previously marketed as VIOXX, rofecoxib has a well-established efficacy and safety profile in migraine, including in patients who were unresponsive to other NSAIDs
• Tremeau’s expanded development program is supported by robust patent protection for TRM-201 through 2040

CONCORD, Mass.–(BUSINESS WIRE)–Tremeau Pharmaceuticals today announced it has successfully opened an investigational new drug (IND) application and received a May Proceed Notification from FDA to expand the development program for TRM-201 (rofecoxib), an investigational non-opioid treatment, to include a Phase III program for acute migraine. Previously marketed as VIOXX, rofecoxib is a cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug (NSAID) with a well-established efficacy profile in multiple indications, including acute migraine.

Migraine is estimated to affect approximately 12% of the U.S. population. It is the second most disabling condition worldwide, and affects many aspects of everyday life.^1,2 NSAIDs are often used alone or in combination with other therapies as the standard of care for patients with migraine. However, some people cannot or prefer not to take NSAIDs because of their inhibitory effect on platelet aggregation, gastrointestinal (GI) adverse effects, or for lack of efficacy. Additionally, despite lacking a formal indication, opioids are also frequently used to treat acute migraines.³

Charles Argoff, MD, a Neurologist at Albany Medical Center in New York, said: “Many patients with migraine use an NSAID for rapid relief. A treatment option such as rofecoxib, with demonstrated once-daily efficacy, a rapid onset of action, no effect on platelet aggregation, and reduced risk of GI adverse effects, could be valuable in the treatment of migraine and uniquely suited to meet the needs of the large number of patients who suffer from migraine and cannot tolerate or do not respond to traditional NSAIDs.”

Tremeau expects that the development program for TRM-201 will include one Phase III acute efficacy and safety study in migraine.

Rofecoxib has a demonstrated an efficacy profile in migraine, regardless of whether or not there was a history of prior response to other NSAIDs.⁴ Rofecoxib has been shown to easily cross the blood-brain barrier, and has been shown to have no effect on platelet aggregation, even at supra-therapeutic doses.^4,5 Rofecoxib was the only COX-2 selective NSAID ever approved in the U.S. to demonstrate a reduced risk of GI bleeding versus a traditional NSAID.⁶

Tremeau’s oral tablet formulation of rofecoxib, TRM-201, has been shown to reach maximum plasma concentrations (median T_max) at two hours after dosing (versus three hours for historical VIOXX),⁷ which Tremeau believes could lead to faster onset of action, a critical attribute for people suffering from migraine.

“The FDA’s clearance of our IND for the Phase 3 testing of TRM-201 in acute migraine reinforces our position that rofecoxib, at the appropriate dose, has no unique safety issues relative to other NSAIDs and potentially several unique benefits,” said Bradford C. Sippy, Tremeau’s Chief Executive Officer. “Our strong intellectual property position, underpinned by the recent issuance of U.S. patents covering TRM-201’s dosage strength and its highly purified rofecoxib active ingredient, affords us the opportunity to expand our development program to help patients suffering from migraine whose needs are not satisfied by currently available NSAIDs.”

Tremeau’s expanded development program is supported by U.S. Patent No. 10,945,992 (expiring May 2040), which covers 17.5 mg solid-dosage forms of rofecoxib, and U.S. Patent No. 10,987,337 (expiring December 2039), which covers purified forms of rofecoxib.

About TRM-201 (Rofecoxib)

TRM-201 is an investigational non-opioid pain treatment containing rofecoxib. Previously marketed as VIOXX, rofecoxib was shown to be a highly potent cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug, or NSAID, with a well-established efficacy profile in multiple indications, including acute migraine. Rofecoxib has been shown to have greater blood-brain barrier penetration than any COX-2 selective NSAID currently available in the U.S., and has demonstrated efficacy in migraine regardless of whether or not there was a history of prior response to other NSAIDs.^4,5 Rofecoxib was shown to have no effect on bleeding time and was the only COX-2 selective NSAID ever approved in the U.S. to demonstrate a reduced risk of gastrointestinal bleeding versus a traditional NSAID in a controlled trial.⁶ VIOXX was voluntarily withdrawn from the market in 2004 due to concerns about cardiovascular safety. It has since been demonstrated in multiple, often industry-independent studies that cardiovascular safety is a dose- and duration-dependent risk of all NSAIDs.^8-13

TRM-201 is currently being studied in a Phase III trial for hemophilic arthropathy, a painful and degenerative joint disease caused by recurrent intra-articular bleeding in patients with inheritable bleeding disorders. Tremeau has gained agreement with FDA that it has established comparable levels of rofecoxib exposure for 17.5 mg of TRM-201 compared with 25 mg of the previously marketed version of VIOXX.

About Tremeau Pharmaceuticals

Tremeau is a Massachusetts-based pharmaceutical company focused on providing non-opioid pain treatments for well-defined patient populations with significant unmet needs.

Tremeau’s unique approach to acute and chronic pain in select conditions is rooted in the mechanism of action, documented efficacy, and clinically differentiated profile of COX-2 selective NSAIDs.

Tremeau’s lead clinical stage product, TRM-201 (rofecoxib), is a COX-2 selective NSAID and a potent non-opioid analgesic with a well-established benefit-risk profile.

VIOXX is a registered trademark of Tremeau Pharmaceuticals, Inc.

¹ Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41(7):646-57.

² Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, Burden, and Comorbidity. Neurol Clin. 2019 Nov;37(4):631-649.

³ Lee JH, et al. Geographic variation in the use of triptans and opioids for the acute treatment of migraine attacks. Headache. 2021; 61: 1499– 1510.

⁴ US Food and Drug Administration. VIOXX (Rofecoxib) U.S. Prescribing Information May 09, 2016, (accessed October 1, 2019).

⁵ Dembo G, et al. Anesthesiology 2005; 102:409–15.

⁶ US FDA. 2005; Summary Minutes of the Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee.

⁷ Schwartz JI, et al. Pharmacokinetic evaluation of rofecoxib : comparison of tablet and suspension formulations. Clin Drug Investig. 2003;23(8):503-9.

⁸ US Food and Drug Administration. Analysis and recommendations for agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders

⁹ Cannon CP, Curtis SP, FitzGerald GA, et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 2006; 368: 1771–81.

¹⁰ Nissen SE, et al. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med 2016: 2519-2529.

¹¹ Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382: 769–79.

¹² Patrono C, Baigent C. Nonsteroidal anti-inflammatory drugs and the heart. Circulation 2014;129:907–916.

¹³ McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med 2011; 8: e1001098.

Contacts

Madeline Russo, 804-621-3222

[email protected]