Welcome to your weekly digest of approaching regulatory and clinical readouts. Given Neurocrine Biosciences’ previous misses in Tourette’s syndrome, in the T-Forward trial in adults and the T-Force Green trial in children and adolescents, observers might be forgiven for any low expectations around the upcoming T-Force Gold trial.
The 120-patient phase IIb study is due to read out by the end of this year and uses Neurocrine’s Ingrezza to treat paediatric Tourette’s syndrome. Ingrezza is already approved in tardive dyskinesia (TD) and Neurocrine will be pointing to this regulatory achievement to steady investor nerves.
However, the path ahead for Tourette’s will be much tougher than that for TD. Tourette’s symptoms, which include involuntary tics, are much more varied between individuals, and there is a higher probability of a strong placebo effect. Questions also remain as to whether the VMAT2 inhibitor’s mechanism of action, particularly its reliance on dopamine regulation, will work in all Tourette’s patients.
That said the approved treatments are less than satisfactory and range from muscle relaxants all the way through to antipsychotics, whose use is often contraindicated in children. If Ingrezza can provide an effective and safer alternative for younger patients commercial success would beckon.
At the time of the T-Forward failure, Neurocrine supporters argued that adult and child Tourette’s populations were very different, pointing out that a lot of children outgrow Tourette’s. As for the failure of T-force Green, Neurocrine suggested that this could have been down to the low dose of Ingrezza used. T-Force Gold is similar to the failed T-Force Green, with the same primary endpoint, reduction in tic severity, but tests substantially higher doses.
Upping the dose is a sensible move, but there is a risk that Neurocrine’s initial caution was justified and that higher doses could have adverse effects in a paediatric population. Neurocrine’s unwillingness to disclose the doses used in the failed T-Force Green trial and in T-Force Gold – apparently for competitive reasons – makes this risk hard to quantify.
At the moment analysts are not betting big on Ingrezza in Tourette’s. Sales by indication forecasts compiled by EvaluatePharma show $1.5bn of Ingrezza’s sales in 2024 coming from TD, compared with just $251m for Tourette’s.
|Late-stage Tourette’s products|
|Project||Company||Mechanism of action|
|THX-130||Therapix Biosciences||Cannabinoid receptor agonist|
|Austedo||Teva Pharmaceutical Industries||Vesicular monoamine transporter 2 inhibitor|
|Ingrezza||Neurocrine Biosciences||Vesicular monoamine transporter 2 inhibitor|
|Ecopipam||Merck & Co/Emalex Biosciences||Dopamine D1 receptor antagonist; Dopamine D5 receptor antagonist|
|THX-110||Therapix Biosciences/Catalent||Cannabinoid receptor agonist|
|ABX-1431||Abide Therapeutics||Monoacylglycerol lipase inhibitor|
|SNC-102||Synchroneuron||Gamma-aminobutyric acid receptor agonist|
Three years after the first phase III trial of Redhill Biopharma’s anti-infective Talicia hit its endpoints, topline data from the second are due. Unlike the Eradicate Hp trial, which used historical controls, Eradicate Hp2 has an active comparator, potentially giving Redhill a harder bar to clear.
Talicia, formerly known by the code RHB-105, is a combination of two antibiotics, amoxicillin and rifabutin, with the proton pump inhibitor omeprazole. It is intended to clear up infection with Helicobacter pylori in patients who have not responded to prior therapy. This is the bacterium that causes gastric ulcers, but Redhill hopes that Talicia will become the first drug indicated for the treatment of H pylori infection regardless of patients’ ulcer status.
The pill burden of the 444 patients in Eradicate Hp2 is high, with those in both arms having to take four capsules every eight hours; patients in the control arm receive amoxicillin plus omeprazole. The study’s endpoint is eradication of H pylori, as confirmed via carbon-13 urea breath test between 43 and 71 days after initiation of treatment. The treatment phase lasts two weeks.
The first phase III study of Talicia, Eradicate Hp, the project cured H pylori infection in 89.4% of patients, easily beating the rate in the control group, 70%. But the control consisted of historical records of eradication rates with amoxicillin plus the antacid lansoprazole. The different proton pump inhibitor used and lack of an active comparator mean a read-across to Hp2 is limited.
Analysts from Lifesci Capital write that they expect Hp2’s treatment arm to demonstrate similar activity to that in the first phase III study, adding that Redhill has powered the Hp2 assuming an 83% efficacy rate. All depends on the eradication rate with the control.
If Eradicate Hp2 is successful, Redhill says it will complete the package required by the FDA, allowing a US filing in early 2019. With qualified infectious disease product designation from the FDA, approval would mean priority review and eight years of US market exclusivity. EvaluatePharma’s consensus forecasts put 2024 sales of Talicia at $293m.