Roivant announces positive NEPTUNE study results for brepocitinib in non-infectious uveitis

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Roivant and Priovant Therapeutics this week announced positive results from the Phase 2 NEPTUNE study (NCT05523765) evaluating brepocitinib in non-anterior non-infectious uveitis (NIU.

According to a news release, the NEPTUNE study enrolled 26 subjects with active NIU who were randomized 2:1 to brepocitinib 45 mg once daily or brepocitinib 15 mg once daily. Patients, physicians, and the study team were blinded to dose. All subjects received a 60 mg/day prednisone burst at study entry for two weeks and were tapered off prednisone per protocol by week 8 (6-week steroid taper).

The study noted that participants were evaluated for treatment failure, a registrational composite endpoint comprising multiple measures of ocular inflammation and visual acuity, as well as discontinuation due to intercurrent events or initiation of rescue therapy. The study's primary efficacy endpoint was the treatment failure rate at week 24.¹

Matt Gline, CEO of Roivant, pointed out the NIU data underscore Roivant’s continued commitment to developing effective medicines in underserved indications with high unmet need, such as for these patients who are at risk of blindness.¹

“We are extremely pleased to share these positive data,” he said in the news release.

Gline also noted the company is pleased to unveil its authorized share repurchase program, and its agreed repurchase of all shares owned by Sumitomo Pharma.

“This transaction along with further potential buybacks reduces shareholder concentration and efficiently retires shares, increasing our continuing shareholders’ exposure to developments in NIU and to the rest of our upcoming clinical data and company progress,” Gline added.

The study noted that at week 24, 29% (5/17) of subjects in the brepocitinib 45 mg arm and 44% (4/9) of subjects in the brepocitinib 15 mg arm met treatment failure criteria, with lower failure rates reflecting greater treatment benefit. The treatment failure rate from disease activity (discontinuations censored) was 18% in the brepocitinib 45 mg arm. These observed results represent approximately twice the observed benefit as seen in the corresponding registrational study for the only approved non-steroidal therapy in NIU^.1

Moreover, the company noted that all week 24 secondary efficacy endpoints, including haze grades, visual acuity, and macular thickness, were also positive and dose responsive. Of patients in the brepocitinib 45 mg arm who met the threshold for uveitic macular edema at baseline, 43% achieved resolution of macular edema by week 24. No patients in the brepocitinib 45 mg arm who entered the study without macular edema developed macular edema by week 24.¹

According to the study, safety and tolerability were consistent with prior clinical studies of brepocitinib, with no new safety or tolerability signals identified. Brepocitinib has been dosed in more than 1400 subjects and patients with a safety profile that appears consistent with approved and widely prescribed JAK inhibitors. The company noted that additional safety and efficacy data will be presented at a future medical conference.

Quan Dong Nguyen, MD, MSc, FARVO, FASRS, NEPTUNE investigator and Professor of Ophthalmology at the Byers Eye Institute, and Professor of Medicine and Pediatrics at Stanford University School of Medicine, explained that non-infectious uveitis is a devastating disease that can lead to severe visual impairment and contribute to tens of thousands of cases of legal blindness in the United States each year, including many instances of irreversible blindness.

“Current treatment options provide inadequate benefits to many patients; thus, novel pharmacotherapeutic agents with better efficacy and more convenient methods of administration are urgently needed,” Nguyen said in the news release. “Brepocitinib’s striking results on multiple endpoints of clinical significance position the drug to become a potentially transformative once-daily oral therapy for this debilitating disease and reinforce the distinctive mechanistic benefits of dual TYK2/JAK1 inhibition for highly inflammatory autoimmune diseases with multiple pathogenic cytokines, such as non-infectious uveitis.”

Ben Zimmer, CEO of Priovant, pointed out the company’s NEPTUNE study was designed to minimize likelihood of false signals of benefit, by tapering patients with active disease from 60 mg/day of prednisone to 0 mg/day in just 6 weeks, more than twice as fast as steroid tapers in precedent studies.

“Against that backdrop, we are thrilled to see a failure rate of only 29% in the brepocitinib 45 mg arm, better than any precedent study was able to achieve even with more lenient tapers,” he said in the news release. “The magnitude and consistency of dose-dependent benefit across multiple independent measurements of inflammation, visual acuity, and macular edema give us high confidence heading into Phase 3.”

Zimmer pointed out the results also point to a potentially highly differentiated product profile for brepocitinib in NIU—an orphan indication with high prevalence, severe morbidity, and few other therapies approved or in development.

The company noted it intends to initiate a Phase 3 program in NIU in the second half of calendar year 2024. The company would like to thank all of the investigators and patients who participated in the NEPTUNE study.

The ongoing Phase 3 study evaluating brepocitinib in dermatomyositis is expected to be fully enrolled in the third calendar quarter of 2024, with data expected in calendar year 2025.

Common share repurchase program

According to a news release, Roivant also announced that its board of directors has authorized a share repurchase program for up to $1.5 billion of the company’s common shares, including the repurchase of all 71.3 million shares held by Sumitomo Pharma at a purchase price of $9.10 per share. The aggregate purchase price for the Sumitomo Pharma transaction is approximately $648.4 million and will reduce Roivant’s shares outstanding as of February 9, 2024 by approximately 9%.

According to the news release, Roivant’s board of directors has authorized a common share repurchase program, allowing for repurchases of Roivant common shares in an aggregate amount of up to $1.5 billion. The repurchase program will be funded with available cash and cash equivalents on hand and does not have an expiration date. The timing and total amount of common shares to be repurchased will depend on several factors, including the market price of the company’s common shares, general business, macroeconomic and market conditions, and other investment opportunities. Under the repurchase program, purchases may be conducted through open market transactions, tender offers or privately negotiated transactions, including the use of trading plans under Rule 10b5-1 of the Securities Exchange Act of 1934, as amended.¹

The company also pointed out that in accordance with the repurchase program, Roivant reached a share repurchase agreement with Sumitomo Pharma to repurchase all 71,251,083 common shares held by Sumitomo Pharma at a purchase price per share of $9.10, for an aggregate purchase price of approximately $648.4 million. The repurchase transaction with Sumitomo Pharma is expected to close on or about April 4, 2024.¹

According to the news release, the repurchase program could be suspended or discontinued at any time. There are no guarantees regarding the number of additional common shares the company will repurchase under the program, if any, or at what prices any purchases will be made.

Reference

1. Roivant Announces Positive NEPTUNE Study Results for Brepocitinib in NIU, as well as Board Authorization for up to $1.5 Billion Share Repurchase Program, Including Repurchase of Entire Sumitomo Pharma. StreetInsider.com. Accessed April 3, 2024. https://www.streetinsider.com/Globe+Newswire/Roivant+Announces+Positive+NEPTUNE+Study+Results+for+Brepocitinib+in+NIU%2C+as+well+as+Board+Authorization+for+up+to+%241.5+Billion+Share+Repurchase+Program%2C+Including+Repurchase+of+Entire+Sumitomo+Pharma/23011474.html