Vitalis Announces Plans for Low-Flush Formulation Fumarate VTS-72 In Multiple Sclerosis

Joseph Habboushe, MD, founder, Vitalis, and emergency medicine physician, NYU Langone

Joseph Habboushe, MD

Vitalis has announced that it plans to commercialize its lead product candidate, VTS-72, a proprietary combination of fumarate and VTS-Aspirin, intended to aid in the treatment of patients with relapsing-remitting multiple sclerosis (MS) who experience dimethyl fumarate flush.¹

Fumarate flush is estimated to occur in up to 40% of patients administered a fumarate agent for the treatment of MS, according to Vitalis. Furthermore, the discontinuation rate due to this adverse effect is believed to be comparable to that of gastrointestinal adverse events (AEs).^2,3

“The fumarate flush is not only prevalent but its impact on patient quality of life and compliance with treatment is often significantly underestimated, exacting both a physical and psychological toll on the patient,” said Joseph Habboushe, MD, founder, Vitalis, and emergency medicine physician, NYU Langone, in a statement. “Flush is also a common side effect of other therapies, such as high-dose niacin, and is known to lead to treatment noncompliance, a high discontinuation rate, and could represent a barrier to initiating patients to fumarate therapy.”

Some literature exists suggesting that pretreatment with aspirin prior to fumarate dosing can reduce flush significantly, though patient adherence to such regimens is low. A 2016 assessment by Rog et al suggested that aspirin could 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.⁴

Notably, a trio of real-world analyses, among other 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.^5-7

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).⁸

Additionally, in the study, 39% of those who experienced flush with dimethyl fumarate ceased to experience flush after using VTS-72.

“Through this propriety combination, we believe that VTS-72 can meaningfully reduce flush while improving the pharmacokinetics of the fumarate, resulting in a potentially significant advancement in the treatment of MS,” Habboushe, who invented the VTS platform, added.

Based on the findings of its open-label study, Vitalis has requested a Type C meeting with the FDA with hopes of launching a pivotal study of its agent in 2020—additionally hoping to submit a new drug application that same year. Thus far, the therapy has already been granted an orphan drug designation for the treatment of patients with MS who experience fumarate flush.

REFERENCES

1. Vitalis Pharmaceuticals Anticipates Launch of Novel Low-Flush Fumarate by 2021 [press release]. New York, NY: Vitalis LLC; Published October 22, 2019. globenewswire.com/news-release/2019/10/22/1933161/0/en/Vitalis-Pharmaceuticals-Anticipates-Launch-of-Novel-Low-Flush-Fumarate-by-2021.html. Accessed October 22, 2019.

2. Bomprezzi R. Dimethyl fumarate in the treatment of relapsing—remitting multiple sclerosis: an overview. Ther Adv Neurol Disord. 2015; 8(1): 20—30. doi: 10.1177/1756285614564152

3. Sejbaek T, Nybo M, Petersen T, Illes Z. Real-life persistence and tolerability with dimethyl fumarate. Mult Scler Relat Disord. 2018;24:42-46. doi: 10.1016/j.msard.2018.05.007.

4. 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. Accessed October 22, 2019.

5. 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.

6. 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.

7. 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.

8. Vitalis. Multiple Sclerosis. vitalispharma.com/multiple-sclerosis. Updated 2019. Accessed October 22, 2019.