Legacy Healthcare has 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).
The upcoming study, known as RAAINBOW-2, is designed as a large, multi-regional, double-blind, placebo-controlled trial that will enroll at least 500 patients with AA. The trial is intended to support a future New Drug Application (NDA) and is positioned as the first topical therapy aimed at treating both moderate and severe forms of the disease. By enabling earlier intervention, Cinainu could help prevent progression to extensive or chronic hair loss, addressing a significant unmet need in current AA management.
Alongside regulatory progress in the United States, Legacy Healthcare has also secured agreement from Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) to conduct the global phase 3 trial, which will include Japanese adult and pediatric patients as young as two years old. The company said it plans to continue discussions with additional health authorities to further expand the geographic reach of RAAINBOW-2.
“Beyond its efficacy, Cinainu has demonstrated the ability to treat autoimmune alopecia areata without immunosuppression-related adverse events and with a persistent effect after treatment discontinuation—both of which, to our knowledge, are firsts,” said Saad Harti, founder and chief executive officer of Legacy Healthcare. He added that FDA-regulated botanical drugs remain an underutilized regulatory pathway, and that the RAAINBOW data support the potential of multi-plant botanical therapies to treat complex chronic diseases without synthetic chemical intervention or long-term health risks. According to the company, Cinainu is the first multi-plant botanical drug candidate to receive FDA clearance to advance into a phase 3 trial.
The FDA’s decision builds on results from the previously completed RAAINBOW phase 2/3 study, which evaluated Cinainu in children and adolescents with moderate to severe AA. Findings published in the British Journal of Dermatology showed clinically meaningful hair regrowth accompanied by a favorable safety profile. Notably, patients maintained clinical benefits even after discontinuing treatment, a distinguishing feature compared with many existing AA therapies that require ongoing use to sustain results. Cinainu has also demonstrated hair regrowth benefits in androgenetic alopecia and persistent chemotherapy-induced alopecia.
Preclinical and clinical research suggests Cinainu exerts pleiotropic biological effects relevant to AA pathogenesis. Studies have shown restoration of peri-follicular anti-apoptotic protein Bcl-2 to near-normal levels, increased epidermal Langerhans cell density, and reduced endothelial expression of inflammatory markers, including interleukin-8, E-selectin, and ICAM-1. Increases in scalp collagen content have also been observed, indicating potential improvements to the follicular microenvironment without broad immunosuppression.
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, as well as Associate Professor of Dermatology at Harvard Medical School. Mostaghimi noted that while recent approvals of oral JAK inhibitors have significantly advanced care for severe AA, there remains a need for a safe, effective, and potentially remittive topical therapy that can be used across the full spectrum of disease severity.
Beyond alopecia areata, Legacy Healthcare is expanding its development pipeline into other dermatologic and inflammatory conditions, including atopic dermatitis and psoriasis, where early efficacy signals have been reported. The company is also investigating an oral formulation of Cinainu for cancer-related fatigue, following encouraging results from an NIH-sponsored preclinical study.
