FDA Issues Complete Response Letter for Vanda Pharmaceuticals' Tasimelteon for Insomnia

Paolo Baroldi, MD, PhD

Credit: Crunchbase

This content originally appeared on our sister site, HCPLive.

According to a recent announcement, the FDA rejected Vanda Pharmaceuticals' supplemental new drug application (sNDA) for tasimelteon (Hetlioz) in the treatment of insomnia.¹

In July 2023, the FDA assigned a PDUF date of March 4, 2024, to make a decision on tasimelteon for insomnia, characterized by difficulties with sleep initiation. A month prior, on February 4, 2024, the FDA identified deficiencies regarding labeling and post-marketing requirements. As a result of these deficiencies, the FDA issued a Complete Response Letter (CRL) stating the submission of tasimelteon could not be approved in the treatment's current form.

The FDA previously approved tasimeleton on January 31, 2014, for non-24-hour sleep-wake disorder in blind individuals.² Tasimeleton is also approved for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome.³

Aiming to assess the effectiveness of tasimelteon for treating insomnia, Vanda Pharmaceuticals completed extensive research. For instance, investigators conducted a phase 3, multi-center, placebo-controlled, 4-week trial (NCT01163032) evaluating 322 patients with primary insomnia.⁴ Patients were randomized to receive either 20 mg or 50 mg of tasimelteon or placebo over 4 weeks.

Investigators sought to assess the immediate and short-term effectiveness of tasimelteon on improving sleep onset as measured by Latency to Persistent Sleep through polysomnography.⁵ The findings showed that patients taking 20 mg and 50 mg of tasimeleton fell asleep 22.9 minutes (P <.001) and 25.9 minutes (P <.001) faster, respectively.

Additionally, investigators conducted 2 transient insomnia studies induced by phase advance of the sleep-wake cycle, with 5-hour and 8-hour phase advance.⁴ These studies revealed that tasimelteon significantly improved sleep parameters on the first night.

“We are excited that the results of this phase 3 chronic insomnia study demonstrate the clinical utility of tasimelteon and the ability of the compound to treat sleep disorders over a period of 4 weeks,” Paolo Baroldi, MD, PhD, the chief medical officer at Vanda, said statement.⁵ “The mechanism of action of tasimelteon as a circadian regulator gives Vanda the opportunity to explore its use for the treatment of circadian rhythm sleep disorders as well as chronic primary insomnia.”

REFERENCES
1. Vanda Pharmaceuticals Announces FDA Update for Supplemental NDA for HETLIOZ® in the Treatment of Insomnia. Vanda Pharmaceuticals. March 6, 2024. Accessed March 11, 2024. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://vandapharmaceuticalsinc.gcs-web.com/node/15816/pdf.
2. FDA Approves Hetlioz. Drugs.com. January 2014. Accessed March 11, 2024.https://www.drugs.com/newdrugs/fda-approves-hetlioz-first-non-24-hour-sleep-wake-disorder-blind-individuals-4005.html.
3. FDA Approves Hetlioz (Tasimelteon) For the Treatment of Nighttime Sleep Disturbances In Smith-Magenis Syndrome. Drugs.com. December 2020. Accessed March 11, 2024. https://www.drugs.com/newdrugs/fda-approves-hetlioz-tasimelteon-nighttime-sleep-disturbances-smith-magenis-syndrome-5398.html.
4. Vanda Pharmaceuticals Announces FDA Update for Supplemental NDA for HETLIOZ® in the Treatment of Insomnia. Vanda Pharmaceuticals. February 5, 2024. Accessed March 11, 2024. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://vandapharmaceuticalsinc.gcs-web.com/node/15716/pdf.
5. Phase III Data Show Vanda Pharmaceuticals&#039; Tasimelteon (VEC-162) Significantly Improves Sleep in Patients with Chronic Insomnia. Vanda Pharmaceuticals. Accessed March 11, 2024. https://vandapharmaceuticalsinc.gcs-web.com/news-releases/news-release-details/phase-iii-data-show-vanda-pharmaceuticals-tasimelteon-vec-162.