To date, more than 2,450
patient-years of inclisiran safety data have been accumulated in the ORION programme, a seven-fold (or 2,120
patient-year) increase over the total patient exposure from the ORION Phase 1 and Phase 2 trials.
These results, included in the submission, were well under the requirement specified by the FDA guidance of no more than 1 acute serious bacterial infection per
patient-year.
In the insulin glargine arm, the rate of severe hypoglycemia was 0.01 episodes per
patient-year of exposure versus 0.003 episodes per
patient-year for standard care.
The mean number of nights with detected hypoglycemia was 21 (4-42) per
patient-year, or 6% of all nights.
The linearized reoperation rates per
patient-year were 0.62% and 2.32% in the mechanical and biological groups, respectively (p = 0.0003).
Comparison of the estimates by individual guideline shows that the practices resulting in the largest
patient-year gains were increasing patient albumin above 40 g/L and reducing facility catheter use to below 10%.
To date, more than 1,899
patient-years of safety data have been accumulated in the ORION Phase III program, a five-fold (or 1,560
patient-year) increase over the total patient exposure from the ORION Phase I and Phase II trials.
The rate of recurrent VTE was 1.3% per
patient-year (95% confidence interval [CI], 0.0% - 4.7%) in the warfarin-treated group and 27.4% per
patient-year (95% CI, 12.9% - 39.4%) in the placebo group.
After a median follow-up of 3.6 years, there were 13 local recurrences, for an ipsilateral recurrence rate of 2.4% per
patient-year, or a 5-year rate of 12%.
Becattini reported that a VTE recurrence occurred in 28 patients in the aspirin group (6.6% per
patient-year) and in 43 patients in the placebo group (11.0% per
patient-year).
This analysis concluded that the risk of serious infections was 0.015 cases per
patient-year of exposure to adalimumab, 0.014 per
patient-year for various dosages of etanercept, and 0.018 per
patient-year for infliximab.
On the basis of existing treatment data from these HSCT-TMA patients and a further 20 cumulative
patient-years of data from other patients treated with nomacopan, Akari is working with the FDA Model Informed Drug Development Program to optimize the pediatric dosing with nomacopan for the planned pivotal HSCT-TMA trial.
