Cemdisiran has been a possible candidate drug for aHUS for some time. Alnylam the pharmaceutical company responsible for its development, withdrew from an earlier trial for it to be used for aHUS unable to recruit enough candidates for a phase 3 study.
In the past 48 hours a new trial has been announced on Clinicaltrials.gov ( click here to read ) “Eculizumab to Cemdisiran switch in aHUS (DANCE)”. The estimated start date is September 2019 and it is expected to be concluded by 2022.
The trial is being sponsored by the Mario Negri Institute for Pharmaceutical Research in Ranica ,Bergamo, Italy. Twelve aHUS patients are expected to be recruited to take part in “double blind” study when withdrawing from Eculizumab. Some patients will receive Cemdisiran and others a placebo.
The official title of study is “A Phase II, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Cemdisiran (ALN-CC5) Following Withdrawal of Chronic Eculizumab Therapy in Patients With Atypical HUS at High Risk of Recurrence”
“Cemdisiran has been designed to reduce the level of C5 mRNA in the liver, thereby reducing levels of circulating C5 protein, inhibiting terminal complement pathway activity, and preventing formation and deposition of the MAC (C5-b9) on endothelial cells in the kidney”
It “knocks out” C5.
It is delivered subcutaneously every four weeks. Some of the trial participants will receive a placebo (labelled as cemidisiran). Those receiving the placebo would return to eculizumab if their aHUS returns.
The prime outcome is the relative activation, between those with cemdisiran versus those with placebo, of Complement activity as measured using a specific blood test- i.e. ex vivo complement activation on the surface of cultured microvascular endothelial cells exposed to patient sera.
Time Frame: Changes from baseline measured at 16,32,44,60, 84 and 108 weeks after randomisation.
This is an eculizumab withdrawal “PLUS” study and could lead to a novel strategy for withdrawal from eculizumab ( and ravulizumab?) for those with a high risk of recurrence.
The clinical contact for this trial is Dr Erica Daina, who the alliance met on its visit to Mario Negri Expert Centre last year ( report of visit here) and who is in the featured image.