利用一种罕见病的临床数据支持另一种罕见病的药物审批

非典型溶血性尿毒症综合征（aHUS）是一种极其罕见的遗传疾病，会导致全身小血管内异常血凝块的形成，从而导致肾衰竭、其他器官损伤和过早死亡。在项目开始时，美国食品及药物管理局尚未批准治疗 aHUS 的药物。此外，由于每年只有几千名 aHUS 患者被确诊，因此很难招募到足够的参与者来开展临床试验。

However, the FDA had approved a humanized monoclonal antibody (mAb), eculizumab, to treat a related, rare, life-threatening disease – paroxysmal nocturnal hemoglobinuria (PNH), which is characterized by destruction of red blood cells and excessive blood clotting. Both aHUS and PNH symptoms result from chronic, uncontrolled complement system activation. Knowing eculizumab’s mechanism of action for PNH suggested that it could confer clinical benefit in aHUS.

解决方案

晚期临床

Therapeutic specialty

罕见/孤儿病

Products

定量药理学

A population PK model for eculizumab, which had been previously constructed for adult PNH patients, was repurposed to determine dosing for aHUS patients. The mAb’s PK/PD relationship in PNH was also leveraged to determine drug exposure and inform pediatric aHUS dosing.

Two small Phase II studies and a retrospective observational study were conducted, involving just 57 aHUS patients. PK/PD modeling of those data was used to determine the dose- response-effect relationships for two surrogate endpoints. Then, trial simulations based on that modeling were used to determine the best dosing for pediatric and adult patients with aHUS.

Patients with aHUS who were treated with eculizumab had improved platelet counts and other blood parameters and better kidney function with some patients no longer requiring plasmapheresis. The FDA approved eculizumab to treat both adult and pediatric aHUS patients.

Trial simulations were used to determine the best dosing for pediatric and adult aHUS patients.

Headquartered in the U.S., our client has been a leader in the discovery, development, and commercialization of medicines for rare diseases for nearly 30 years. Its research efforts focus on novel molecules and targets in the complement cascade, and it operates in more than 50 countries.