Travere Therapeutics, Inc.

The FDA is yet to approve a therapy specifically for FSGS. \n Orphan drug specialist Amicus Therapeutics is paying Dimerix $30 million cash for U.S. rights to the phase 3 prospect DMX-200, establishing it as a challenger to Travere Therapeutics in a rare kidney disease. New Jersey-based Amicus’ hunt for de-risked assets that could address a significant unmet medical need led it to Australia. Melbourne-based Dimerix began a phase 3 study of the CCR2 inhibitor DMX-200 in focal segmental glomerulosclerosis (FSGS) kidney disease in 2022. The Australian biotech recently aligned with the FDA on the use of proteinuria as an appropriate primary endpoint for traditional approval. Dimerix reported interim results on the effect of DMX-200 on proteinuria last year. With enrollment well underway and another interim analysis coming up, data that could support filings for FDA approval is in sight.As the program advances, Amicus could pay Dimerix up to $75 million in development and regulatory milestones. A further $35 million is tied to the first sale of the drug. Beyond that, Amicus has committed up to $410 million in sales milestones and $40 million tied to potential future indications.   The FDA is yet to approve a therapy specifically for FSGS. That could change soon. Travere filed for FDA approval of Filspari in the indication this March. Amicus’ willingness to bet on DMX-200 despite the potential of a rival that is near approval reflects a belief that there is room for multiple approaches in FSGS.Jeffrey Castelli, chief development officer at Amicus, said on an earnings call Thursday that DMX-200 “is specifically targeting the inflammatory signaling in the damaged kidney.” Other molecules, in contrast, are focused on hemodynamics. Some patients will respond better to one drug than the other, Castelli said, and physicians will try to figure out which is the right approach for each individual.  “With DMX-200, there are ways you can look at how much the inflammatory component is driving things. Those are going to be the patients we\'re going to see respond best in the trials, and those are going to be the patients that I think doctors will want to focus on,” Castelli said. ChemoCentryx, now part of Amgen, was developing a CCR2 inhibitor with Vifor Fresenius Medical Care Renal Pharma until a phase 2 flop scuttled the FSGS program in 2020. Castelli discussed the differences between DMX-200 and earlier candidates, contrasting attempts to directly inhibit MCP-1 binding to the downstream approach of Dimerix’s molecule. “What happened with traditional binding inhibitors is MCP-1 couldn\'t dock. It actually led to a rebound effect where MCP-1 levels dramatically increase, which then would compete with the inhibitor and kind of lead to a muting effect,” Castelli said. “The beauty of the downstream blocking is that MCP-1 can still dock. That leads to MCP-1 degradation.”Amicus believes the mechanism of DMX-200 will “really maximize the ability to shut down the monocyte inflammation,” Castelli said. The downstream effects will also allow “monocytes to continue their job elsewhere ... so they can still fight infections as they should outside of the kidney.”

Amicus Therapeutics has paid $30 million cash upfront to license US rights to a late-stage therapy for a rare kidney disease from the Australian biotech Dimerix. The deal provides for milestone payments of $560 million plus royalties, according to a Thursday release . The asset, codenamed DMX-200, is a small molecule chemokine receptor 2 inhibitor intended to treat focal segmental glomerulosclerosis (FSGS). In March 2024, Dimerix said that early data from the first 72 patients in a pivotal Phase 3 trial had shown DMX-200 to be better than placebo at cutting high levels of protein in the urine — a sign of poor kidney function — and that there were no safety concerns. Another blinded interim analysis of the ACTION3 trial, which will continue to be conducted and funded by Dimerix, is planned. Final data could emerge in 2027. A positive readout would trigger a milestone payment. This, plus another payment on FDA approval of the pill in FSGS, could total $75 million, the companies said. Amicus will pay a further $35 million on DMX-200’s first sale for the condition, and further commercial sales milestones could total up to $410 million. Amicus is also on the hook for percentage royalties from the low-teens to low-twenties on DMX-200’s US sales. The companies are looking beyond FSGS too, with Dimerix also eligible for up to $40 million in milestone payments for potential future indications. The drug has other entailments, having been licensed to Taiba Middle East for various Middle Eastern countries, but Dimerix retains the rights in other territories. There are currently no FDA-approved FSGS therapies, but DMX-200 may not become the first. That honor could go to Travere Therapeutics’ Filspari, which was filed for the condition in March. Travere said in February it would go ahead with the filing despite Filspari’s pivotal FSGS trial having failed. The endpoint of the Filspari trial, however, was different from ACTION3’s, and Dimerix’s trial might have a better chance of succeeding. The FDA has agreed that a reduction in proteinuria would be sufficient for DMX-200’s approval, Amicus and Dimerix said. In Phase 2, DMX-200 demonstrated a 24% cut in proteinuria after four months’ treatment, which translated to 17% on a placebo-adjusted basis, though that finding was based on just seven evaluable patients. ACTION3 is much bigger, aiming to enroll about 286 subjects by the end of this year. Meanwhile, Filspari managed an absolute cut in urine protein levels of 44.8% after two months in its Phase 2 trial and a 50% drop after two years of treatment in Phase 3. Leerink analysts estimate that there are 15-30,000 FSGS patients in the US, and wrote that “with rare disease pricing, this could be a multi-blockbuster opportunity.”

4月29日，CSL Vifor和Travere宣布，欧盟委员会已将针对IgA肾病的药物FILSPARI (sparsentan)从有条件批准转为标准上市许可。此决定基于III期PROTECT研究的完整数据，该研究显示FILSPARI能显著减缓肾功能衰退。这一进展是IgA肾病患者的重要一步，确保了在欧盟、冰岛、列支敦士登和挪威的全面上市。IgA 肾病是一种罕见的进行性肾脏疾病。它是由免疫球蛋白 A（IgA）在肾脏中异常沉积引起的。IgA 本应帮助身体抵抗感染，但当它异常沉积时，会导致肾脏正常的过滤机制受损，进而引起尿中带血（血尿）、尿中出现蛋白质（蛋白尿）以及肾功能的进行性丧失。其他症状还可能包括水肿和高血压。FILSPARI®（sparsentan）是一种创新、非免疫抑制的单分子药物。它是唯一一种双重内皮素血管紧张素受体拮抗剂（DEARA），对内皮素 A 受体（ETAR）和血管紧张素 II 1 型受体（AT1R）具有高选择性。这种独特的作用机制使其在 IgA 肾病的治疗中展现出潜力。FILSPARI 由 Travere 公司开发，并在英国、欧洲和美国获得了治疗 IgA 肾病的孤儿药认定。CSL Vifor 公司则获得了 FILSPARI 在欧洲、澳大利亚和新西兰的独家商业化权利。目前，FILSPARI 在欧盟有条件上市许可后，已在德国、奥地利和瑞士上市。这项标准上市许可的决定，得到了关键的 III 期 PROTECT 研究数据的有力支持。PROTECT 研究是迄今为止 IgA 肾病领域规模最大的介入性研究之一，也是针对这种罕见肾病进行的唯一一项头对头对照试验。评估了 400 mg 剂量的 sparsentan 与 300 mg 剂量的厄贝沙坦（一种血管紧张素 II 受体阻滞剂 ARB）的安全性及有效性。研究共纳入了 404 名年龄在 18 岁及以上、患有 IgA 肾病且尽管接受了至少最大标签剂量 50% 及最大耐受剂量的 ACEI 或 ARB 治疗后仍存在持续蛋白尿的患者。在预设的中期分析中，PROTECT 研究达到了其主要终点，具有统计学意义。•治疗 36 周后，接受 FILSPARI 治疗的患者与基线相比，蛋白尿平均降低了 49.8%，而厄贝沙坦治疗组的平均降低幅度为 15.1%。•研究的两年确证结果显示，与厄贝沙坦相比，FILSPARI 治疗在 eGFR 慢性斜率终点上达到了统计学意义，并显示出具有临床意义的肾功能保护作用。eGFR 是一种测量肾脏过滤血液中废物能力的血液测试。•治疗期间出现的不良事件在 sparsentan 组和厄贝沙坦组之间基本平衡，但 sparsentan 组中头晕和低血压的情况相对更多。这些数据证明了 FILSPARI 在减缓 IgA 肾病患者肾功能下降方面的潜力。识别微信二维码，可添加药时空小编请注明：姓名+研究方向！