CHMP Recommends Approval of Givosiran for AHP in Europe
The Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency (EMA), has recommended approval of Alnylam Pharmaceuticals’ givosiran for treating acute hepatic porphyria (AHP) in adults and adolescents 12 and older.
If approved by the European Commission, givosiran will start to be sold in Europe under the brand name Givlaari. The medication recently was approved for the same indication in the U.S.
“Today’s CHMP positive opinion is very encouraging news for patients living with acute hepatic porphyria and recognizes the potential of givosiran to address the urgent unmet need that exists for those living with this ultra-rare, inherited disease,” Barry Greene, president of Alnylam Pharmaceuticals, said in a press release.
“We are committed to bringing givosiran to patients in Europe as rapidly as possible,” Greene said.
Givosiran, formerly known as ALN-AS1, is an investigational RNA-based therapy designed to block the activity of the aminolevulinic acid synthase 1 (ALAS1) enzyme, which is overactive in AHP patients, to prevent the accumulation of toxic compounds in cells. RNA is generated from DNA and used as a template for protein production.
The therapy previously received priority medicines, or PRIME, accelerated assessment and orphan drug status from EMA.
CHMP’s recommendation was based on positive findings from a pivotal, Phase 3 clinical trial (NCT03338816) called ENVISION.
The study evaluated the safety and effectiveness of givosiran in 94 AHP patients, including 89 with acute intermittent porphyria (AIP). Participants were assigned randomly to receive either givosiran at a dose of 2.5 mg/kg, or placebo, administered by a subcutaneous (under-the-skin) injection once a month for six months.
Latest data from ENVISION presented at the 54th Annual International Liver Congress of the European Association for the Study of the Liver (EASL) showed givosiran was able to reduce the average number of annual AHP attacks by 74%, compared to the placebo.
In addition, givosiran lowered the levels of aminolevulinic acid (ALA) and porphobilinogen (PBG), two key biomarkers of AHP, in the patients’ urine by 92% and 89%, respectively. Treatment also was found to be safe and to improve participants’ overall health status and quality of life.
After completing the trial, 93 patients chose to continue treatment with givosiran for an additional 30 months in the study’s open-label extension study.
Updated findings from the extension study showed the reduction in the annual rates of attacks, and in ALA urine levels, seen during ENVISION in patients receiving givosiran continued during the extension study. Moreover, the therapy’s safety profile in the extension study was consistent with findings from the original trial.
“We have seen in clinical trials that givosiran has the potential to reduce the frequency of attacks, reduce pain and improve patients’ quality of life. Today’s recommendation takes us a significant step closer to making an important new treatment option a reality for AHP patients in Europe,” said Bernhard Kaumanns, head of Medical Affairs, Europe, Middle East, Africa and Canada, at Alnylam.
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