Ionis Pharmaceuticals Reports Positive IONIS-TTR Rx Data At XV Intl. Symposium On AMyloidosis

Ionis Pharmaceuticals, Inc.

announced today positive results from two ongoing trials with IONIS-TTRRx: Ionis Pharmaceuticals (PRNewsFoto/Ionis Pharmaceuticals, Inc.) An ongoing investigator-sponsored, open-label Phase 2 study in patients with TTR amyloid cardiomyopathy, which includes patients with familial amyloid cardiomyopathy (FAC) and patients with wild-type transthyretin amyloidosis (wt-TTR amyloidosis). The data in a subset of patients treated with IONIS-TTRRx for 12 months were presented today (abstract # O-72) by the lead investigator, Merrill D. Benson, M.D., at the XV International Symposium on Amyloidosis (ISA) in Uppsala, Sweden. In addition, new data from the ongoing open-label extension (OLE) study of IONIS-TTRRx in patients with familial amyloid polyneuropathy (FAP) who have completed dosing in the Phase 3 NEURO-TTR study presented in a poster at ISA on July 5 showed that both wild-type and mutant TTR levels were substantially reduced and that the reductions observed were approximately equal in magnitude regardless of the presence or location of the mutation. Phase 2 Investigator-initiated (Benson) Open-label Study Results "Data from multiple endpoints support cardiomyopathy disease stabilization in patients treated with IONIS-TTRRx. The MRI data demonstrated disease stabilization, as measured by left ventricular mass, as compared to both baseline values and from our published1 natural history data. The observation of disease stabilization in patients treated for 12 months with IONIS-TTRRx, differs from what we observed in our recent natural history study, which used the same MRI measurements to follow disease progression over a year," said Merrill D. Benson, M.D., professor of pathology and lab medicine, medical and molecular genetics at Indiana University School of Medicine. "Last year, we reported similar data on the first three patients in the study to achieve 12 months of dosing with IONIS-TTRRx. These new data, which now include a total of eight patients out of 22 enrolled who have now been treated with IONIS-TTRRx for 12 months, support and extend our previous observations." Patients entering the Phase 2 IONIS-TTRRx study had baseline interventricular septum thickness (IVS) ≥1.3cm. In this study, patients receive one injection of IONIS-TTRRx once a week. The first eight patients treated with IONIS-TTRRx had a mean decrease of 4 percent in left ventricular mass from baseline as measured by MRI at 12 months. This compares favorably to Dr. Benson's published natural history study in similar patients with an IVS ≥1.3cm at study entry who had a mean increase of 14 percent in left ventricular mass as measured by MRI at 12 months. Patients in the Phase 2 IONIS-TTRRx study also demonstrated evidence for disease stabilization in multiple additional endpoints at 12 months, including, IVS thickness, global strain, the cardiac biomarker B-type natriuretic peptide (BNP) and the functional endpoint, 6-minute walk test (6MWT). Safety and tolerability data were presented on all of patients treated with IONIS-TTRRx in the Phase 2 IONIS-TTRRx study (n=22). No drug related serious adverse events have been reported. Three patients developed the need for cardiac pacing. Moderate decreases in platelets were observed in some patients, but no serious platelet declines have been observed to date in this study. Injection site reactions were predominantly mild and infrequent, occurring in less than 2% of all injections. Transient pruritus was observed in two patients. Two patients reported fatigue lasting two to four days after dosing. The study is progressing and was recently amended to extend treatment from 24 to 36 months.