EC approves Ionis’ amyloidosis drug
Ionis Pharmaceuticals (Nasdaq: IONS) has received marketing authorisation from the European Commission for Tegsedi (inotersen), its RNA-targeted therapeutic for stage 1 or 2 polyneuropathy in adults with hereditary transthyretin amyloidosis (hATTR). This is the first approval for the drug and unusually EU approval has come through ahead of the US, with the outcome of the FDA’s review is due by 6 October. Ionis is the largest shareholding of Swiss investment trust BB Biotech (accounting for 9.8% of its NAV) and is also held by other specialist vehicles including International Biotechnology Trust (IBT).
The approval was based on the pivotal Neuro-TTR phase III study, which showed Tegsedi improved the modified Neuropathy Impairment Score +7, a measure of disease progression, and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy. The study also established that clinical benefit associated with substantial reductions in the transthyretin (TTR) protein, the underlying cause of hATTR amyloidosis, regardless of the mutation type or stage of disease. hATTR amyloidosis is a progressive, systemic and ultimately fatal disease, where misfolded TTR builds up in various tissues and organs resulting in progressively debilitating symptoms.
Tegsedi is directly owned by Ionis’ 75%-owned Akcea Therapeutics (Nasdaq: AKCA) subsidiary, which is focused on the development of drugs for rare diseases. Akcea has a pipeline of six drugs, all licensed from Ionis: Tegsedi, Waylivra (volanesorsen), AKCEA-APO(a)-LRx, AKCEA-ANGPTL3-LRx, AKCEA-APOCIII-LRx, and AKCEA-TTR-LRx. Waylivra is under regulatory review for familial chylomicronemia syndrome, an ultra-rare disease caused by impaired function of the enzyme lipoprotein lipase. The condition is characterised by severe hypertriglyceridemia and a risk of unpredictable and potentially fatal acute pancreatitis. The outcome of the FDA’s review of Waylivra is due by 30 August and has been reviewed by an advisory committee, which voted 12-8 in favour of approval in May. The drug is also in Phase III studies for familial partial lipodystrophy.
AKCEA-APO(a)-LRx ,which is subject to a strategic collaboration with Novartis, is in a Phase II study for treatment of cardiovascular disease in patients with high Lp(a) with results expected by the end of the year. Novartis has an option to licence the product, in which case it will be responsible for all future development activities including conducting a global Phase III cardiovascular outcome study. AKCEA-ANGPTL3-LRx is in a Phase II trial for familial partial lipodystrophy with results due shortly; AKCEA-APOCIII-LRx is in Phase II for hypertriglyceridemia with results due next year. AKCEA-TTR-LRx, which is intended for hereditary and wild-type ATTR, is expected to enter the clinic in 2018.
Ionis recently formed a 10 year strategic collaboration with Biogen to develop new antisense drugs for neurological diseases, building on the two companies’ existing collaboration that produced Spinraza (nusinersen) for spinal muscular atrophy. Ionis received $375m in cash and a $625m equity investment from Biogen. Each of the up to 10 programmes that Biogen can opts in to could generate up to $270m in milestones and royalties on sales of mid teens to 20%.