Jazz Acquires Narcolepsy Hopeful DSP-0187 in Agreement With Sumitomo Pharma

Rob Iannone, MD, MSCE

According to a recent announcement, Jazz Pharmaceuticals and Sumitomo Pharma have entered into an agreement to codevelop and cocommercialize Sumitomo’s investigational sleep disorder treatment, DSP-0187. The molecule will be referred to as JZP441 by Jazz.¹

DSP-0187 is a potent and highly selective oral orexin-2 receptor agonist that Sumitomo has been developing. It is currently being assessed in a single-dose phase 1 study in narcolepsy (jRCT2071210103), conducted in Japan, that kicked off in November 2021. That study is evaluating the pharmacokinetics, safety, and tolerability in healthy volunteers.^1,2 Jazz noted that it plans to rapidly advance DSP-0187’s development based on the findings.

The treatment has shown potential application as a therapy for narcolepsy, as well as idiopathic hypersomnia and other sleep disorders. DSP-0187 is initially expected to be evaluated in narcolepsy, according to Jazz.

Rob Iannone, MD, MSCE, executive vice president, global head of research and development, Jazz Pharmaceuticals, said in a statement that the agreement illustrates Jazz’s ability to identify compounds of promise as well as the company’s “corporate objective of making strategic, value-creating investments in our pipeline."

"Orexin agonism is an exciting area of sleep disorder research and an approach that may be complementary to oxybate therapy. We believe that DSP-0187 has the potential to advance the treatment of narcolepsy and other sleep disorders based on its profile," Iannone added in the statement.¹ "As a leader in sleep medicine, we are committed to delivering innovative therapies to people who are living with debilitating sleep disorders. We look forward to leveraging our expertise in sleep disorders to rapidly advance this promising therapy into clinical trials in the US and Europe.”

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Orexins, neuropeptides have a role in sleep and wakefulness regulation, are a class with a few recently FDA-approved members for the treatment of insomnia. Notably, in late 2019, the FDA approved lemborexant (Dayvigo; Eisai), a small molecule orexin receptor antagonist that binds to both orexin receptor 1 and 2, for the treatment of insomnia in adults.³ Then, a few months ago, in January 2022, the agency gave the go-ahead to daridorexant (Quviviq; Idorsia), a dual orexin receptor antagonist, for the treatment of insomnia in adults. Daridorexant became available for use in the US on May 3, 2022.^4,5

This will expand Jazz’s portfolio into the orexin class. As of now, the company’s list of approved agents includes a number of therapies for sleep disorders, such as its combination calcium, magnesium, potassium, and sodium oxybates, also known as JZP-258 (Xywav), which was the first therapy approved for idiopathic hypersomnia; sodium oxybate oral solution (Xyrem), which is approved for narcolepsy; and solriamfetol (Sunosi), which is approved for the treatment of excessive daytime sleepiness in adults with narcolepsy or obstructive sleep apnea.

In early January 2022, Jazz released additional positive data from its supporting phase 3, double-blind study (NCT03533114) of JZP-258, which demonstrated clinically meaningful and statistically significant differences compared with placebo in both the primary end point—change in Epworth Sleepiness Scale (ESS) score—and several other secondary end points. A total of 154 adults with idiopathic hypersomnia, aged 19 to 75 years, were included in the study and dosed for 3 periods. First, patients completed an open-label period on the study drug for 10-14 weeks to determine optimal dosing, after which patients received stable, optimized doses of JZP-258 for 2 weeks, with a median of 4.5 grams nightly (interquartile range [IQR], 3.0-5.0) for 21 patients on 1-dose regimen and 7.5 grams nightly (IQR, 6.5-8.1) for 93 patients on 2-dose regimen. The remaining 40 patients changed dosing regiments 1 or more times.^6,7

Patients then entered the double-blind randomized withdrawal period (DBRWP), where they received either the optimized dose or placebo for 2 weeks and were evaluated on changes in ESS scores beginning from the end of the stable dose period (SDP). During the DBRWP, ESS scores increased (representing a status worsening) in participants randomly assigned to placebo but remained stable in those assigned to JZP-258 (least squares mean difference: –6.5 [95% CI, –8.0 to –5.0]; P <.0001).⁷

Under the terms of this agreement with Sumitomo, the company will receive an upfront payment of $50 million, and will retain its commercialization and development rights in the Asia and Pacific territories, as well as Japan and China. Jazz, on the other hand, has licensed those rights in the United States, Europe, and other associated territories.¹

"DSP-0187 is a potent, highly selective oral orexin-2 receptor agonist, which is a novel small molecule compound originally created by Sumitomo Pharma by utilizing our advanced expertise in drug discovery for central nervous system disorders. We are pleased to partner with Jazz on DSP-0187 given their strong track record of development success and commercial execution in sleep disorders and long-term commitment to advancing therapies to improve the lives of people with sleep disorders," Toru Kimura, representative director and executive vice president, Sumitomo Pharma, said in a statement.¹ "Jazz's accomplishments in sleep medicine make the company an ideal partner for us as DSP-0187 enters its next phase of development."

REFERENCES
1. Jazz Pharmaceuticals and Sumitomo Pharma Announce Exclusive License Agreement to Develop and Commercialize DSP-0187, a Potent, Highly Selective Oral Orexin-2 Receptor Agonist. News release. Jazz Pharmaceuticals. May 4, 2022. Accessed May 5, 2022. https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-and-sumitomo-pharma-announce-exclusive-license-agreement-to-develop-and-commercialize-dsp-0187-a-potent-highly-selective-oral-orexin-2-receptor-agonist-301537690.html
2. Development Pipeline. Sumitomo Pharma website. Updated January 31, 2022. Accessed May 5, 2022. https://www.sumitomo-pharma.com/rd/clinical/pipeline.html
3. US FDA approved Eisai’s Dayvigo (lemborexant) for the treatment of insomnia in adult patients. News release. Eisai. December 23, 2019. Accessed May 5, 2022. https://eisai.mediaroom.com/2019-12-23-U-S-FDA-Approves-Eisais-DAYVIGO-TM-lemborexant-for-the-Treatment-of-Insomnia-in-Adult-Patients
4. Idorsia recieves US FDA approval of Quiviviq (daridorexant) 25 and 50 mg for the treatment of adults with insomnia. News release. Idorsia. January 10, 2022. Accessed May 5, 2022. https://www.biospace.com/article/releases/idorsia-receives-us-fda-approval-of-quviviq-daridorexant-25-and-50-mg-for-the-treatment-of-adults-with-insomnia/?s=85
5. George J. Idorsia's recently approved insomnia drug Quviviq hits the shelves. Philadelphia Business Journal. May 3, 2022. Accessed May 5, 2022. https://www.bizjournals.com/philadelphia/news/2022/05/03/insomnia-idorsia-quviviq-radnor-fda-switzerland.html
6. Lancet Neurology publishes positive, pivotal phase 3 data of Xywav (Calcium, magnesium, potassium, and sodium oxybates) oral solution for idiopathic hypersomnia. News release. Jazz Pharmaceuticals. January 5, 2022. Accessed May 5, 2022. https://www.prnewswire.com/news-releases/lancet-neurology-publishes-positive-pivotal-phase-3-data-of-xywav-calcium-magnesium-potassium-and-sodium-oxybates-oral-solution-for-idiopathic-hypersomnia-301454171.html
7. Dauvilliers Y, Arnulf I, Foldvary-Schaefer N, et al. Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomized withdrawal study. Lancet. 2022;21(1):53-65. doi:10.1016/S1474-4422(21)00368-9