New Positive Clinical Results for Givosiran (ALN-AS1) in Acute Intermittent Porphyria Patients with Recurrent Attacks

New Positive Clinical Results for Givosiran (ALN-AS1) in Acute Intermittent Porphyria Patients with Recurrent Attacks

We reported interim results from our ongoing Phase 1 study with givosiran at the 2017 International Congress on Porphyrins and Porphyrias (ICPP), held June 25 – 28, 2017 in Bordeaux, France. Data presented were from the first three unblinded cohorts from Part C, in patients with acute intermittent porphyria (AIP) that experience recurrent attacks and initial data from the open-label extension (OLE) study.

Read our press release
View the complete Phase 1 interim and OLE data presentation
View the results from the EXPLORE natural history study
View the poster on healthcare utilization and costs
View the poster on disease burden in patients with AIP and recurrent attacks

Patients treated with givosiran (N=9) experienced a mean 63 percent reduction in the annualized number of all porphyria attacks relative to the run-in period attack rate, with consistent effects observed across a wide range of baseline attack rates. Evaluating only attacks that were treated at a healthcare facility or with hemin, givosiran administration was associated with a mean 73 percent reduction in annualized attack rate relative to placebo during the treatment period. A 73 percent mean decrease in annualized hemin doses relative to the run-in period was also reported. Additionally, in a new analysis, the observed reduction in annualized attack rate was found to be associated with the degree of ALA and PBG lowering.

Further, initial results from Cohorts 1 and 2 (N=8) of the givosiran OLE study were also presented; to date, all eligible patients have rolled over from the Phase 1 study to the OLE study. These data showed that that longer-term treatment with givosiran was associated with consistent reductions in the annualized porphyria attack rate.

Importantly, as of the data cutoff date, givosiran administration was generally well tolerated in recurrent attack AIP patients in Cohorts 1-3 in Part C of the Phase 1 study and in Cohorts 1 and 2 of the ongoing OLE study, with a mean of 169 and 111 days on study, respectively, and up to 12 months on givosiran. In Part C there were no drug-related serious adverse events (SAEs) or discontinuations due to adverse events (AEs). Excluding porphyria attacks, three patients had four SAEs; none were assessed as related to study drug. As previously reported, one death occurred in a patient in cohort 3 in the givosiran arm due to hemorrhagic pancreatitis complicated by a pulmonary embolism and following a recent hospitalization for bacteremia; the death was considered to be unlikely related to study drug by the investigator and the study’s Safety Review Committee. During the Phase 1 treatment period, all randomized patients reported at least one AE.

The majority of AEs were assessed as mild or moderate in severity. Twenty-five percent of patients had severe AEs, assessed as unrelated to study drug. AEs in three or more patients included: abdominal pain, headache, nasopharyngitis, nausea and vomiting. Four patients were assessed as having AEs possibly related to study drug, including injection site reaction (mild and self-limiting), hypersensitivity, myalgia, headache, moderate renal impairment (in a patient with a history of moderate renal impairment) and erythema. There were no other clinically significant changes in vital signs, electrocardiograms, clinical laboratory parameters (including liver function tests and lipase tests), or physical examination. The overall safety experience in the ongoing OLE study was consistent with results from the Phase 1 study. No SAEs (excluding porphyria attacks) or discontinuations due to AEs have been reported in the OLE study.

Separately, updated 12-month data from EXPLORE – a prospective, multinational, observational study characterizing the natural history and clinical management of acute hepatic porphyria (AHP) patients with recurrent attacks or who receive hemin prophylaxis to prevent attacks – demonstrate that patients suffer from both acute attacks and chronic symptoms in between attacks, that together result in a diminished quality of life. The annualized attack rate on study was approximately 5 attacks per person with a mean attack duration of 7 days. The majority of attacks (77 percent) required treatment in the hospital, urgent healthcare facility or with intravenous hemin.

Further, in the first analysis of its kind for AHP in the U.S., an analysis of direct costs associated with AHP and recurrent attacks revealed the average estimated annual expenditure per patient ranges from approximately $400,000 to $650,000 of direct costs.

We believe these latest datasets further support givosiran’s potential to transform the treatment of patients suffering from acute hepatic porphyrias, and we look forward to continuing our efforts in rapidly developing givosiran towards regulatory filings and, if approved, to patients.



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