Date: 2017-01-05
Type of information: Submission of a clinical trial application
phase: 3
Announcement: submission of a clinical trial application
Company: Cymabay Therapeutics (USA - CA)
Product: arhalofenate
Action
mechanism: antiinflammatory agent. Arhalofenate is an anti-inflammatory uricosuric drug that reduces the risk of gout flares while also lowering serum uric acid (sUA). Arhalofenate is the first compound in a new class of gout therapy that the CymaBay refers to as Urate Lowering Anti-Flare Therapy (ULAFT). CymaBay licensed rights to arhalofenate in the U.S. to Kowa Pharmaceuticals America, but retains rights to develop and commercialize arhalofenate outside the U.S.
Disease: gout
Therapeutic area: Inflammatory diseases
Country:
Trial details:
Latest
news: * On January 5, 2017, CymaBay Therapeutics announced that it has successfully concluded its scientific advice discussions with the European Medicines Agency (EMA) on the Phase 3 development program for arhalofenate. Agreement was reached on the efficacy endpoints for the two separate clinical actions of arhalofenate. The sUA lowering will be assessed as responder rates for patients achieving the targets of <6 and <5 mg/dL for chronic and tophaceous gout, respectively. The data could support an indication for the management of hyperuricemia associated with gout in combination with febuxostat in these two patient populations. Flare data will be collected with an electronic diary and assessed using the same flare definition successfully used in the Phase 2 program. These data could support an indication for flare prophylaxis. In total, these studies will enroll approximately 1300 patients intended to receive treatment for at least 6 months. Approximately half of these patients will receive arhalofenate and will enter into an extension phase for an additional 6 months to collect safety information. The lowest dose at which febuxostat (Adenuric®) is approved in Europe is 80 mg. In order to provide information on the relative effectiveness of the combination of arhalofenate and febuxostat (40 mg), a fourth study in subjects with chronic gout will be conducted comparing flare rate of this combination with that of febuxostat (80 mg) alone. The duration of this study would be 6 months and will enroll approximately 150 subjects. * On January 20, 2016, CymaBay Therapeutics announced that it has successfully concluded its end-of-phase 2 meeting discussions with the FDA on the Phase 3 development program for arhalofenate. Correspondence with the FDA subsequent to the formal end-of-Phase 2 meeting has resolved the remaining details of the Phase 3 design. CymaBay reached agreement with the FDA on all of the key elements of a Phase 3 program that would support registration. The program would include two Phase 3 studies of arhalofenate in combination with febuxostat in patients with chronic gout and a third study in tophaceous gout, a more advanced form of the disease in which patients have deforming nodular deposits of urate crystals in soft tissues and joints referred to as tophi.
CymaBay reached agreement with the EMA on all of the key elements of the planned Phase 3 program which is very similar to that agreed upon with the FDA last year. It will include two pivotal studies of arhalofenate in combination with febuxostat (40 mg) in patients with chronic gout and a third study in combination with febuxostat (80 mg) in subjects with tophaceous gout, a more advanced form of the disease.
Agreement was reached on coprimary efficacy endpoints for the two separate clinical actions of arhalofenate. The sUA lowering would be assessed as responder rates for patients achieving the targets of <6 and <5 mg/dL for chronic and tophaceous gout, respectively. The data could support an indication for the management of hyperuricemia associated with gout in combination with febuxostat in these two patient populations. Flare data will be collected with an electronic diary and assessed using the same flare definition successfully used in the Phase 2 program. These data could support an indication for flare prophylaxis. In addition, agreement was reached on the methodology to be used for assessing the resolution of tophi in patients with tophaceous gout.
In total, the agreed upon Phase 3 program would enroll approximately 1300 patients intended to receive treatment for at least 12 months. Each Phase 3 study would consist of three parallel arms to assess the sUA and flare endpoints after 6 months of treatment. Patients in arm 1 would receive the combination of arhalofenate and febuxostat, those in arm 2 febuxostat alone together with flare prophylaxis (NSAID or colchicine) and those in arm 3 febuxostat alone. The dose of arhalofenate would be 800 mg in all three studies. For the two trials in chronic gout, the febuxostat dose would be 40 mg, while in the tophaceous gout study, it would be 80 mg. No arhalofenate monotherapy arms are required in the Phase 3 program. The coprimary sUA endpoint would be assessed by comparing the responder rates for arm 1 vs. the combined arms 2 and 3 in each of the three studies. The coprimary flare rate endpoint would be assessed by comparing arm 1 vs. 3, while a secondary flare rate endpoint would be a comparison of arm 1 vs. 2, in each of the three studies. It was agreed that a safety database of approximately 650 patients treated with the arhalofenate-febuxostat combination for 12 months would be sufficient, together with efficacy data, to assess the risk benefit profile.
