PURPOSE: R667 is an orally active, gamma selective, retinoid receptor agonist. In contrast to to all trans retinoic acid ATRA , a potent pan agonist agonist with no retinoid receptor selectivity and a different PK profile, R667 showed improved efficacy in promoting structural lung repair and functional improvement in animal models of emphysema with fewer side effects. Two clinical studies are now extending that evaluation as a potential treatment for human emphysema.
METHODS: REPAIR Study (Retinoid Treatment of Emphysema in Patients on the Alpha 1-Antitrypisn International Registry): This 1 year study has completed enrollment in Europe for 260 patients with CT-proven emphysema (AATDe). Patients receive either 5 mg orally daily or placebo in a 1:1 randomization . TEγSRA Study (Treatment of Emphysema with gamma Selective Retinoid Agonist): This 2 year study began enrolling in 1Q 07 in US and EU/Africa for 480 exsmokers with moderate to severe COPD and CT-proven emphysema (COPDe). 5 mg orally daily or placebo in a 2:1 randomization is used in addition to a long acting bronchodilator and ICS ‘optimal therapy’ regimen.
RESULTS: Outcome Measures: Both studies will measure structural, functional and symptomatic outcomes: CT lung density, FEV1, Dl,CO, lung volumes, 6MWT or shuttle walk test,, SGRQ, and dyspnea index. A fully integrated biomarker program is planned for each study to identify systemic markers of disease and response to retinoid treatment. Additional pharmaco-genetic profiling is planned for the TEγSRA study. Safety in both studies is monitored by an independent monitoring board. 4 quarterly reviews to date in the REPAIR study all confirmed the evolving safety profile of R667 5mg/day is adequate for study continuation.
CONCLUSION: These are the first clinical trials of a selective retinoid agonistassess the safety and effect of treatment on lung structure, pulmonary function and symptoms in patients with emphysema and, therefore, may represent a novel approach to the treatment of this disease.
CLINICAL IMPLICATIONS: N/A (Phase 2 Studies in Progress).
DISCLOSURE: Paul Kvale, No Financial Disclosure Information; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. These are Phase 2 Studies of an investigatonal drug.