EASL 2019 – Alnylam presents the benefits of givorisran

The Envision study of givosiran treatment for acute hepatic porphyria of Alnylam was already known to have shown a significant reduction in life-threatening attacks badociated with this disease. Today, at EASL, the company has revealed to experts the extent of this benefit.

The average annualized rate of composite attacks has decreased by 74% compared to placebo, a figure that should impress doctors and put regulators at ease with granting authorization. However, three serious security events mean that it is not a dead certificate.

Nevertheless, all but one of the 94 recruited subjects chose to participate in a long-term extension study, suggesting that patients with severe forms of HPA consider that givosiran is a therapy that should be tried.

Another important point to remember is that only 50% of patients were without attack, compared to 16% for placebo. Dr. Manisha Balwani, the lead investigator of Envision who presented the data to reporters at the conference yesterday, declined to comment on responses observed in the other half of patients, claiming that the data had not yet been completely badyzed patient by patient. based.

This is certainly an issue that regulators will want to have an answer to, while security will be scrutinized. The three serious safety events – high fever, kidney failure and elevated liver enzymes – had already been announced last month.Alnylam claims victory in givosiran despite fears of toxicity, March 6, 2019).

Theresa Heggie, Alnylam's first vice-president for Europe and Canada, pointed out that kidney and liver problems could be a burden for this disease, but she acknowledged that she could not exclude an effect of givosiran.

"Transitional changes in [signals of kidney disease] resolved, and that encouraged us. And in these patients we continued to measure liver enzymes and they normalized. We believe that the benefit / risk ratio is very favorable to givosiran, "she said. Advantage at EASL.

Many concerns about the underlying toxicity issues related to the company's RNAi technology platform are looking forward to seeing what regulators will do with these signals.