Q&A: New data further show long-term efficacy of Givlaari for AHP

Alnylam Pharmaceuticals Inc. reported new data from the open-label extension period of the Envision phase 3 study that further demonstrated the long-term therapeutic benefit of Givlaari in patients with acute hepatic porphyria.

During the interim analysis of the open-label extension (OLE) period, Givlaari (givosiran) showed maintained efficacy and safety through 12 months of treatment, according to Alnylam’s press release. The company also reported a potential for improved efficacy over time.

The purpose of the Envision phase 3 study was to assess the efficacy and safety profile of givosiran in patients with AHP. Givosiran reportedly met the primary endpoint in the 6-month double-blind period. According to the release, there was a 74% reduction in annual rate of composite porphyria attacks. After the double-blind period was completed, 93 eligible patients out of 94 patients were enrolled in the OLE period and received givosiran at 2.5 mg/kg or 1.25 mg/kg.

All patients will transition to the 2.5 mg/kg dose level because the evidence points to increased efficacy at a higher dose, according to the release.

Healio Gastroenterology spoke with Eliane Sardh, MD, PhD, study investigator from the Porphyria Centre Sweden, Centre for Inherited Metabolic Diseases Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden on some of the key results from the OLE period. Sardh had initially presented the results during a webinar Alylam Pharmaceuticals hosted.

Healio: What is take-home message of the study?

Sardh: New 12-month interim data from the OLE period of the Envision phase 3 study confirm the long-term therapeutic benefit of givosiran in patients with acute hepatic porphyria (AHP) who experience recurrent acute AHP attacks. AHP is a family of rare, genetic disorders involving defects in distinct heme biosynthesis pathway enzymes. The disease manifests in acute, potentially life-threatening neurovisceral attacks, with severe abdominal pain being the most common symptom.

The most common type of AHP is acute intermittent porphyria (AIP). There is a relatively high incidence of individuals with mutations associated with AIP, but the disease clinically manifests in less than 10% of the at-risk population, with an even smaller percentage of patients experiencing recurrent acute attacks.

This recurrent patient population often faces disability and social isolation, as they are unable to hold full-time work or pursue studies due to chronic pain, fatigue and constant admittance to hospital for treatment.

Healio: What were the 12-month interim data results from the Envision study?

Sardh: Results show that the efficacy and safety of givosiran were maintained through 12 months of treatment, with sustained or enhanced reduction in AHP attacks over time. Continued treatment with givosiran in the OLE period (6-12 months) led to sustained reduction in the annualized rate of composite porphyria attacks (AAR) with a median AAR of 0. The proportion of attack-free patients receiving givosiran increased from 50% in the double-blind period to 61.7% in the first 6 months of the OLE period. Sustained lowering of aminolevulinic acid and porphobilinogen levels — the toxic heme synthesis intermediates believed to be causal for the disease manifestations of AHP — in the OLE period was accompanied by durable reductions in hemin use, lower levels of daily pain and ongoing improvements in self-reported quality of life. The safety profile of givosiran was consistent with that observed in the double-blind period, and there were no new safety findings.

Healio: Will the results impact treatment of patients with AHP?

Sardh: These results provide further evidence that treatment with givosiran has the potential to significantly reduce the high burden of disease for patients and families affected by recurrent AHP.

Healio: What is the next step in research?

Sardh: We’re continuing to monitor patients in the OLE period of the Envision phase 3 study to generate additional data about the long-term efficacy and safety of givosiran.