Welcome to your weekly digest of approaching regulatory and clinical readouts. Intercept Pharmaceuticals is looking for its first approval in liver disease, and it will need to hope that the FDA is comfortable enough with the well-known itching side effect and changes in cholesterol levels to give its blessing for obeticholic acid in primary biliary cirrhosis (PBC).
Shire, meanwhile, is nearing readout of phase II trials for SHP607 to prevent retinopathy of prematurity, a condition that can blind pre-term infants. Success with this protein complex would help the UK-headquartered group build an ophthalmology franchise, led by lifitegrast.
OCA in PBC
Obeticholic acid (OCA) has made its name in non-alcoholic steatohepatitis (NASH), but PBC is the first indication in which it has a chance at approval. If the FDA signs off, OCA would be the first new agent in this condition in 50 years.
Ursodeoxycholic acid, sometimes called ursodiol, is the main treatment in this condition, although around half of patients do not respond. OCA has a different mechanism of action, targeting the farnesoid X receptor, and has shown itself to reduce elevated liver enzymes in patients with PBC.
The effectiveness in changing liver biochemistry markers comes with a side effect of itchiness, which is already a complication of PBC regardless of treatments. Recent long-term safety data released at the AASLD meeting suggested that the majority of patients taking 10mg daily experienced itchiness; most occurred in the first month, so a strategy of titrating from 5mg to 10mg after several months of treatment has emerged.
The FDA has set a decision deadline of February 29, 2016, to decide on approval. No advisory committee has been announced; the agency has tentatively scheduled a meeting of the gastrointestinal drugs panel for January 13, although there is no suggestion that OCA would be the topic.
OCA is forecast to sell $541m in PBC in 2020, according to EvaluatePharma’s sellside consensus. This is a useful revenue stream, and certainly one that Intercept will welcome. However, NASH is the bigger prize, with the indication expected to generate $1.2bn in sales in 2020 after a launch in 2019.
In NASH, the FDA has asked for a major outcomes study to determine whether OCA can reverse fibrosis and delay or resolve other symptoms. With a primary endpoint at 18 months, that study is not likely to read out until late 2017 at the earliest.
Approval in PBC would help provide revenue to fund the NASH trial, not to mention reinforce Intercept bulls’ belief that NASH will be a success. It could also serve as a catalyst for big pharma to take a chance on a takeout of Intercept, although its current $3.7bn valuation may still seem pricey for companies looking to enter the NASH space, in spite of its decline since early 2014 (Boom! Trial halt turns Intercept into an improbable midcap company, January 10, 2014).
The paediatric eye project SHP607 has the potential to be the second string for Shire’s ophthalmology bow assuming that the lead agent, lifitegrast, gets a more positive FDA reception the second time around (Shire keeps it simple and gets dry eye win, October 27, 2015).
SHP607 is targeting retinopathy of prematurity, a condition that results from disruption of normal blood vessel growth. In many cases this resolves itself, but in severe cases leaking and bleeding can occur, along with scarring that causes the retina to be pulled away from the rest of the eye.
The agent is also known as mecasermin rinfabate, which was sold as a growth failure drug inder the name Iplex before withdrawal as a result of a patent dispute. Shire acquired rights to it in eye disease through its buyout of the Swedish company Premacure.
Shire’s 120-patient phase II trial aims to show that treatment with SHP607 will reduce severity of retinopathy in premature babies at what would be full term – those treated with the Shire candidate will be compared with untreated controls.
The drug is forecast to sell $111m in 2020, according to the EvaluatePharma consensus. By comparison lifitegrast has an estimate of $756m, although in a much bigger disorder, dry eye.
The combined sales of the two projects are expected to constitute 9% of Shire’s total sales in 2020, which will be a useful addition as the group continues its shift away from dependence on attention deficit/hyperactivity disorder pills.