Alnylam is set to file for accelerated FDA approval of givosiran on the strength of interim data from a phase 3 trial. The readout linked the ALAS1-targeted RNAi to a statistically significant drop in urinary aminolevulinic acid (ALA), a biomarker Alnylam and the FDA think may predict clinical benefit.
Massachusetts-based Alnylam is set to deliver topline data against its primary endpoint of annualized attack rate early next year. But, with the FDA showing a willingness to fast track promising drugs on the strength of preliminary data, the gene silencing leader is aiming to bag an accelerated approval using biomarker data from the first 43 acute hepatic porphyria patients enrolled in the trial.
Alnylam thinks the interim data support that plan. The biotech is yet to share data from the ongoing trial but revealed givosiran has outperformed placebo against the ALA biomarker endpoint over the first part of the trial. The difference between the two arms amounted to a p value of less than 0.001.
In an indication of how perceptions of the FDA’s approach have changed, Alnylam plans to discuss the findings with the agency with a view to filing for accelerated approval around the end of the year, rather than hold off on approaching the agency until it has the primary endpoint data. Taking the accelerated approach could result in givosiran getting to patients around six months earlier.
To pull off the accelerated plan, Alnylam will need to convince the FDA that the preliminary results and unmet need are strong enough to justify the risks involved in approving the drug using interim data.
Alnylam is yet to say much about the efficacy side of the equation beyond the 0.001 p value but has shared details of the safety profile seen so far. One-fifth of patients taking givosiran suffered serious adverse events—compared to 10% in the placebo arm—and one subject dropped out levels of a liver enzyme soared. The liver enzyme levels of the patient who dropped out later returned to normal.