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
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.