A Letter to Shareholders Regarding the Benson FDA Warning Letter
May 10, 2017 – There has been some confusion and misunderstanding about an FDA warning letter that was issued in March of this year to Dr. Merrill Benson following an investigation of his site, specifically in regard to his independent investigator-initiated study (IIS) in patients with TTR cardiomyopathy. We would like to clarify some of the facts about this letter.
1. The FDA warning letter is NOT in regard to the completed Phase 3 NEURO-TTR study in patients with familial amyloid polyneuropathy (FAP). The pivotal NEURO-TTR Phase 3 study is complete and we are on track to announce data this quarter.
2. The warning was issued because of an inadequate response by Dr. Benson’s site to issues the FDA investigation raised.
3. Dr. Benson has provided further detail to the issues raised in the warning letter in his response to the FDA and the study is ongoing.
4. No patient in Dr. Benson’s IIS has had a serious platelet event.
The main reason for the warning letter was to inform Dr. Benson that his response to issues raised in the FDA investigation for “failure to perform protocol-required procedures, including clinical laboratory tests used to monitor subject safety and tolerability” was not adequate and further detail from Dr. Benson was needed. Dr. Benson subsequently responded and the study has continued throughout this process.
In May and June last year, new platelet monitoring procedures were being implemented following the report of a small number of cases of serious platelet events in two of our Phase 3 studies. During this time, the FDA investigation found protocol deviations in Dr. Benson’s IIS, including some instances where a few patients were not monitored as required. Dr. Benson has confirmed he has now implemented routine monitoring for all patients in the study and the study is ongoing.
Dr. Benson’s site is also involved in the NEURO-TTR study. Ionis has audited Dr. Benson’s site multiple times as part of our regular oversight of the NEURO-TTR program and no significant issues have been identified.
ABOUT DR. BENSON’S INVESTIGATOR INITIATED STUDY
As a reminder, Dr. Benson’s study is an independent investigator-initiated study in patients with familial amyloid cardiomyopathy (FAC) and wild-type TTR amyloidosis (wt-TTR amyloidosis) with baseline intraventricular septum (IVS) thickness >= 1.3cm. As previously reported, the first eight patients treated for 12 months with IONIS-TTRRx had a mean decrease of 4 percent in left ventricular mass from baseline