But Ionis Pharmaceuticals' subsidiary presses on with filing plans
Akcea Therapeutics says it plans to file for approval of its drug for rare disease familial chylomicronaemia syndrome (FCS) later this year on the back of positive clinical results – despite the phase III trial revealing some worrying safety considerations.
The results of the APPROACH trial in 66 FCS patients showed that volanesorsen met its objective of achieving a 77% decrease in triglycerides, a significant improvement over the 18% reduction seen with placebo. There was also a reduction in pancreatitis and abdominal pain with the drug, according to Akcea, which is a wholly owned subsidiary of antisense specialist Ionis Pharmaceuticals.
FCS is a rare disease affecting approximately 3,000 to 5,000 patients worldwide, and is caused by a deficiency in an enzyme (lipoprotein lipase) that in turn leads to extremely high triglyceride levels in the blood. Triglyceride-rich particles (chylomicrons) damage the pancreas and other organs such as the liver and spleen.
Volanesorsen tackles the problem by reducing the production of a protein (ApoC-III) that is involved in the regulation of triglycerides, according to Akcea.
The company is upbeat about the prospects for the drug, which is also being developed for familial partial lipodystrophy (FPL), another rare disease characterised by elevated triglyceride levels. The APPROACH results did reveal some worrying safety considerations however, and shares in Ionis slipped after the top-line data was released.
All told, 10 of the 33 patients treated with volanesorsen withdrew from therapy, half because of injection site reactions and half because of reductions in blood platelets (thrombocytopenia).
Three patients developed serious (Grade 4) thrombocytopenia, although Akcea noted these resolved after stopping treatment. Jefferies analysts said the effects on platelets are a concern, however, casting a shadow on otherwise positive results for a disease that at the moment has no approved treatment.
A high drop-out rate will limit the commercial potential for the drug, according to Jefferies' Eun Yang, who sees peak sales of around $150m.
Last year, the FDA placed a clinical hold on Ionis' drug for rare disease TTR amyloid cardiomyopathy because of thrombocytopenia, which was followed by partner GlaxoSmithKline handing back rights to the programme. That led to speculation that platelet effects could be a class issue for Ionis antisense drugs, although the biotech says this is not the case.
Ionis has said since that the TTR amyloid cardiomyopathy phase III trial has restarted and is on course to generate results in the coming weeks.