GlaxoSmithKline (GSK) has decided against launching a Phase III trial in its collaboration with Ionis Pharmaceuticals to develop its IONIS-TTRRx as a treatment for transthyretin (TTR) familial amyloid polyneuropathy (FAP).

Ionis, which disclosed GSK’s decision today, said the pharma giant will assess its options for TTR amyloid cardiomyopathy once additional clinical data are available from ongoing studies.

GSK’s decision comes a month after the FDA placed a clinical hold on the planned Phase III study, called CARDIO-TTR, due to safety findings in an ongoing Phase III study assessing the candidate NEURO-TTR in TTR FAP.

NEURO-TTR is one of two ongoing studies of IONIS-TTRRx,. The candidate is also the subject of a Phase II open-label study in patients with TTR-related amyloid cardiomyopathy initiated by Merrill Benson, M.D., of Indiana University–Purdue University Indianapolis.

Both studies are evaluating patients with TTR-related cardiomyopathy using a cardiac substudy to evaluate patients who have cardiac involvement in addition to their polyneuropathy. Approximately half of the patients in the NEURO-TTR study also have TTR-related amyloid cardiomyopathy.

According to Ionis, both NEURO-TTR and Dr. Benson's study are expected to provide significant data on patients with TTR amyloid cardiomyopathy, which could contribute to the design of an optimal Phase III study.  Both studies are proceeding, Ionis added, with updated data from Dr. Benson's study to be  presented at the International Symposium on Amyloidosis in July, whereas data from the NEURO-TTR study is set for release in the first half of 2017.

Ionis said it is continuing to work with GSK to “actively” prepare for an NDA filing.

In Ionis’ statement today, GSK insisted it was not throwing in the proverbial towel on its long-standing collaboration with Ionis to develop IONIS-TTRRx, or its efforts to treat the rare and fatal disease.

“GSK remains committed to developing innovative medicines for the treatment of amyloidosis and to our ongoing collaboration with Ionis to develop IONIS-TTRRx for TTR amyloidosis,” Helen Merianos, Ph.D., medicine development leader for GSK's TTR amyloidosis program, said in a statement. “We will assess the results from the NEURO-TTR study to inform our next steps for TTR amyloid cardiomyopathy.”

IONIS-TTRRx is an antisense drug designed to reduce the production of TTR. The drug candidate is being developed as a one-injection, once-weekly treatment for all forms of TTR amyloidosis. The FDA has granted IONIS-TTRRx its Orphan Drug Designation with Fast Track Status for patients with FAP, while the European Medicines Agency has granted its Orphan Drug Designation to IONIS-TTRRx for the treatment of patients with TTR amyloidosis.

IONIS-TTRRx is also known as GSK2998728, and was formerly called ISIS- TTRRx until Isis Pharmaceuticals changed its name last year to Ionis. Through March 2015, when IONIS-TTRRx was advanced into Phase II/III, the company generated $60 million in upfront and milestone payments from GSK related to advancing ISIS-TTRRx.

Previous articleAlzheimer’s Protein Not All Bad, Says MassGen Study
Next articleLiterature Review: Finding Better Drug–Drug Combinations Faster