Vitalis’s VTS-Aspirin platform was granted an orphan drug designation to be used in combination with diroximel fumarate and monomethyl fumarate for the treatment of fumarate flush in relapsing multiple sclerosis.
Joseph Habboushe, MD
Vitalis has announced that the FDA has granted an orphan drug designation for its proprietary VTS-Aspirin platform to be used in combination with diroximel fumarate (Vumerity; Biogen) and monomethyl fumarate (Bafiertam; Banner Life Sciences) for the treatment of fumarate flush in patients with relapsing multiple sclerosis (MS).1
“Fumarates, an important class of oral drugs to treat RRMS, cause fumarate flush in as many as 40% of patients,” said Joseph Habboushe, MD, MBA, founder, Vitalis, and inventor of the VTS platform. “This is a significant side effect and can lead to skipping of doses or, in some cases, treatment discontinuation. VTS-72 significantly reduced fumarate flush in an 18-patient pilot study, and we expect to initiate a pivotal trial later this year.”
Habboushe noted that these 2 fumarate salts— diroximel fumarate and monomethyl fumarate —are often used to treat patients with MS, but can cause flush, and thanks in part to the clinical benefit of combining them with aspirin, Vitalis was able to obtain orphan status for both in combination with VTS-Aspirin. He explained that the company believes that by combining the VTS-Aspirin platform with these therapies, the company can provide meaningful tolerability benefits patients.
Vitalis acknowledged that it plans to continue to evaluate the potential of these combinations. “We believe that FDA’s recognition of this subset of patients as an orphan population speaks to the unmet need for an effective method of treating fumarate flush, as our product candidates are the first adult MS therapies to receive orphan designation in over 15 years,” Habboushe said.
Previously, Vitalis received an orphan drug designation for its lead clinical candidate, VTS-72, a proprietary combination of dimethyl fumarate (Tecfidera; Biogen) and aspirin for the treatment of relapsing MS patients who experience fumarate flush.
Some literature suggests that pretreatment with aspirin prior to fumarate dosing can reduce flush in a significant fashion, but adherence to these regimens is a challenge. A 2016 assessment implied that aspirin may play a role in the prevention of bothersome flushing in doses of 75 mg or 150 mg twice daily, though the authors warned that these data did not support routine prophylaxis.2 A trio of real-world analyses, among other published literature, have estimated high rates of discontinuation due to flushing, ranging from 27% to 29% at 12 months, and 44% to 57% at 24 months.3-5
Vitalis stated its belief that VTS-72 can improve fumaric acid pharmacokinetics while easing flush. In a randomized, open-label, 2-way crossover study, VTS-72 was associated with a statistically significant reduction of flush, equaling 63.3% lower rate compared to standard dimethyl fumarate, as measured by the Global Flush Severity Scale, in a cohort of 18 healthy individuals (P = .0018). In the study, 39% of those who experienced flush with dimethyl fumarate ceased to experience flush after using VTS-72.6
1. Vitalis Receives Orphan Drug Designation for Diroximel Fumarate and Monomethyl Fumarate, in Combination with VTS-Aspirin, for Multiple Sclerosis Patients Who Experience Fumarate Flush [press release]. New York, NY: Vitalis Pharmaceuticals; Published April 21, 2020. Accessed April 28, 2020. globenewswire.com/news-release/2020/04/21/2019255/0/en/Vitalis-Receives-Orphan-Drug-Designation-for-Diroximel-Fumarate-and-Monomethyl-Fumarate-in-Combination-with-VTS-Aspirin-for-Multiple-Sclerosis-Patients-Who-Experience-Fumarate-Flus.html
2. Rog D, Cader S, Harrower T, et al. Effect of aspirin on flushing in relapsing-remitting multiple sclerosis patients receiving delayed-release dimethyl fumarate. ECTRIMS Online Library. Published September 16, 2016; 145929; P1246. onlinelibrary.ectrims-congress.eu/ectrims/2016/32nd/145929/david.rog.effect.of.aspirin.on.flushing.in.relapsing-remitting.multiple.html.
3. Mallucci G, Annovazzi P, Miante S, et al. Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study. J Neurol. 2018;265(8):1850-1859. doi: 10.1007/s00415-018-8916-6.
4. Duquette P, Yeung M, Mouallif S, Nakhaipour HR, Haddad P, Schecter R. A retrospective claims analysis: Compliance and discontinuation rates among Canadian patients with multiple sclerosis treated with disease-modifying therapies. PLoS One. 2019;14(1):e0210417. doi: 10.1371/journal.pone.0210417.
5. Eriksson I, Cars T, Piehl F, Malmström RE, Wettermark B, von Euler M. Persistence with dimethyl fumarate in relapsing-remitting multiple sclerosis: a population-based cohort study. Eur J Clin Pharmacol. 2018;74(2):219-226. doi: 10.1007/s00228-017-2366-4.
6. Vitalis. Multiple Sclerosis. Updated 2019. Accessed April 28, 2020. vitalispharma.com/multiple-sclerosis.