Legacy Healthcare Receives FDA Clearance to Advance Cinainu to Phase 3 AA Clinical Trials

This week, Legacy Healthcare announced plans to advance Cinainu, a topical botanical drug candidate, into an international phase 3 clinical trial for the treatment of moderate to severe alopecia areata (AA) following clearance of its Investigational New Drug (IND) application by the US Food and Drug Administration (FDA).¹

Addressing Global Unmet Needs

RAAINBOW-2, a large, multi-regional, double-blind, placebo-controlled trial, will evaluate Cinainu in at least 500 patients with AA and is intended to support a future New Drug Application (NDA). It’s positioned as the first topical drug candidate intended for use across both moderate and severe disease, with the potential to allow earlier intervention before progression to extensive or chronic alopecia, addressing a major gap in current disease management.

In parallel with the regulatory progress in the US, Legacy Healthcare has also received agreement from Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) on the conduct of a global phase 3 trial that will include Japanese adult and pediatric patients as young as 2 years of age. The company has confirmed that discussions with additional health authorities are planned to further expand the geographic scope of RAAINBOW-2.

"Beyond its efficacy, Cinainu has shown to treat autoimmune AA without immunosuppression-related adverse events, and with a persistent effect after treatment discontinuation, both of which, to our knowledge, are firsts," Saad Harti, founder and CEO of Legacy Healthcare, said in a statement. "FDA-regulated Botanical drug is an overlooked regulatory pathway, but the results of the RAAINBOW trial support that a botanical drug can treat complex chronic diseases without synthetic chemical intervention and no long-term health risks. FDA IND clearance to proceed to Phase 3 marks a key milestone in the development of Cinainu and highlights the growing potential of botanical drug innovation. To our knowledge, Cinainu is the first multi-plant botanical drug candidate granted FDA clearance to advance into Phase 3 trial."¹

Clinical Efficacy and Mechanism of Action

Cinainu’s FDA clearance builds on results from the previously completed RAAINBOW phase 2/3 trial conducted in children and adolescents with moderate to severe AA.² The study, published in the British Journal of Dermatology, demonstrated clinically meaningful treatment effects alongside an excellent safety profile. Notably, Cinainu showed sustained clinical benefits even after treatment discontinuation, a finding that distinguishes it from many existing AA therapies, which often require continuous use to maintain response. Cinainu has also demonstrated positive effects on hair regrowth in androgenetic alopecia and persistent chemotherapy-induced alopecia.

Mechanistically, Cinainu has demonstrated pleiotropic biological activity relevant to AA pathogenesis. Preclinical and clinical studies have shown restoration of peri-follicular anti-apoptotic protein Bcl-2 to near-normal levels, increases in epidermal Langerhans cell density, and reductions in endothelial expression of inflammatory mediators such as interleukin-8, E-selectin, and ICAM-1. Additionally, Cinainu has been associated with increased scalp collagen content, suggesting potential benefits for the follicular microenvironment. These effects collectively point toward immunomodulatory and tissue-supportive actions rather than broad immunosuppression.

Future Pipeline Potential

The phase 3 RAAINBOW-2 trial will be led by Arash Mostaghimi, MD, MPH, FAAD, Vice Chair of Clinical Trials and Innovation and Medical Director of the Dermatology Consult Service at Brigham and Women’s Hospital, and Associate Professor of Dermatology at Harvard Medical School.

“The approval of three oral JAK inhibitors over the past 3 years has been a major breakthrough for the treatment of patients with severe AA. However, there still is a need for a safe, effective, and potentially remittive topical therapy for patients with AA across the spectrum of disease severity,” Mostaghimi wrote.¹

In addition to AA, Legacy Healthcare is pursuing pipeline expansion into other dermatologic and inflammatory conditions, including atopic dermatitis and psoriasis, where early efficacy signals have been observed. The company is also exploring an oral formulation of Cinainu for cancer-related fatigue, based on efficacy demonstrated in an NIH-sponsored preclinical study.

References

1. Legacy Healthcare to Advance Topical Solution Cinainu into International Phase 3 Trial for Alopecia Areata following US FDA Clearance. News release. PR Newswire. Published January 6, 2026. Accessed January 7, 2026. https://www.prnewswire.com/news-releases/legacy-healthcare-to-advance-topical-solution-cinainu-into-international-phase-3-trial-for-alopecia-areata-following-us-fda-clearance-302653997.html

2. Blume-Peytavi U et al. Efficacy and safety of Cinainu in pediatric alopecia areata: an international, double-blind, randomized, placebo-controlled, phase 2/3 trial. British Journal of Dermatology. 2025 Jul 16:ljaf279. doi: 10.1093/bjd/ljaf279.