Last week, Ionis’ (NASDAQ:IONS) oncology pipeline got a boost, and yesterday, it was the turn of its cardiovascular division to receive good news. Data from the phase III Compass trial of its antisense triglyceride-lowering project volanesorsen were largely positive, though after a high dropout rate was recorded, safety will be watched closely in upcoming studies.
And another deal with AstraZeneca (NYSE:AZN) has progressed, this time sending IONIS-AZ4-2.5-LRx, now named AZD8233, into preclinical development and netting Ionis $25m in the process. The group had received $28m from Astra from an oncology tie-up on Friday, and the latest milestone is another good, if early, omen for its technology (Patience rewards Ionis and Ziarco, December 19, 2016).
The companies did not give many details about AZD8233, apart from saying it was another antisense project designed to inhibit an undisclosed target to treat cardiovascular disease.
Volanesorsen, meanwhile, is more of a known quantity – it is designed to reduce the production of ApoC-III, a protein that helps regulate plasma triglycerides.
And results from the 113-patient Compass study in severe hypertriglyceridemia suggest that it works. The trial met its primary endpoint, showing a statistically significant 71.2% mean reduction in triglycerides after 13 weeks of treatment compared with a 0.9% reduction in the placebo group.
However, this came at a cost: 13% of patients discontinued because of injection site reactions, while another 7% stopped treatment after what the company termed non-serious adverse events. There was also a case of an allergic reaction that, after an investigation, was deemed likely unrelated to treatment.
The company said there were no "serious platelet events" in the study, without specifying what defined seriousness. Ionis needs to restore confidence in its technology after cases of severe thrombocytopenia with its amyloidosis project IONIS-TTRRx (Ionis safety blow boosts Alnylam, May 27, 2016).
This side effect has also been seen in a trial of volanesorsen in a different disease, the ultra-rare familial chylomicronemia syndrome (FCS), which is set to be volanesorsen’s main indication. That study, called Approach, is due to read out in the first quarter of 2017, so no doubt investors will be keeping an eye on safety as well as efficacy.
The signs from a subgroup of seven FCS patients in Compass are promising: none of them discontinued therapy, and they had a 73% mean reduction in triglycerides after 13 weeks compared with a mean increase of 70% in the placebo group.
Ionis is also studying volanesorsen in another orphan disease, familial partial lipodystrophy, with data from the Broaden trial due in 2019.
The drug is forecast to bring in $490m by 2022, according to EvaluatePharma sellside consensus, making it Ionis’ second-biggest asset after the spinal muscular atrophy project Spinraza. While volanesorsen’s safety profile in Compass was not perfect, it should be acceptable in a rare disease setting – but the group will hope that Approach and Broaden do not uncover anything more worrying.