Welcome to your weekly digest of approaching regulatory and clinical readouts. Jazz Pharmaceuticals expects three phase III studies of its sleep disorder project JZP-110 to read out early next year, and as patent challenges loom for its biggest seller, Xyrem, Jazz needs another moneyspinner.
Also a trial of Johnson & Johnson’s Zytiga follow-up apalutamide is likely to yield data in the first half of next year. The study is in non-metastatic castration-resistant prostate cancer patients who have not received chemo or androgen receptor inhibitors, and here again the company is looking to defend itself against the threat of generics.
Results from three phase III studies of Jazz’s JZP-110, two in sleep apnoea and one in narcolepsy, will appear in 2017. The double-blind, placebo-controlled, sleep apnoea studies in a combined 654 patients are expected to read out in the first quarter of next year.
One of the trials tested four doses (37.5-300mg) of JZP-110 for 12 weeks, and the other was a six-week, flexible-dose, randomised-withdrawal study. The co-primary endpoints of both trials are changes on the Epworth Sleepiness Scale and the maintenance of wakefulness test, measuring the severity of excessive sleepiness and ability to stay awake.
The third study, in excessive sleepiness in narcolepsy, enrolled 240 patients, and three doses of JZP-110 were tested: 75mg, 150mg or 300mg. The co-primary endpoints were the same as in the sleep apnoea trials.
JZP-110 proved effective in phase II in narcolepsy patients, and most adverse events were mild to moderate. The most common were headache, nausea, diarrhoea, insomnia, decreased appetite and anxiety.
A human abuse liability trial showed that JZP-110 was less subject to abuse than phentermine, but still had abuse potential. The company has said it could be scheduled by the DEA as category 4, indicating low to moderate abuse risk, and will likely be positioned as a third-line treatment after generic stimulants.
Bernstein analysts do not view the drug as different from amphetamine in its action via the dopamine receptors, and note that it will likely have moderate commercial success given payer resistance. Forecasts currently sit at $190m by 2022, according to sellside consensus from EvaluatePharma.
Jazz's Xyrem, for excessive daytime sleepiness and cataplexy in narcolepsy, sold $955m last year, making up 72% of the company’s revenue. 2022 sales are forecast to reach $1.6bn, according to EvaluatePharma, but as it faces several patent challenges in the next couple of years Jazz needs to strengthen its pipeline.
This is Sparta!
Data from the phase III trial of Johnson & Johnson’s apalutamide could also appear in the early months of 2017. The Spartan study, which has a primary completion date of December, is testing apalutamide in 1,200 non-metastatic castration-resistant prostate cancer patients.
Apalutamide or placebo is being given as a 240mg tablet once daily alongisde current treatment to patients who are chemo and androgen receptor inhibitor-naive.
The primary measure is metastasis-free survival. Secondary outcomes include overall survival, time to metastasis, progression-free survival and time to initiation of cytotoxic chemotherapy. Trials in combination with niraparib and Zytiga are under way.
In a phase II trial 89% of patients given apalutamide had a PSA decline of at least 50% at week 12. At a median follow-up of 28 months 18 patients (35%) remained in the study, with most discontinuing owing to disease progression or adverse events, the most common of which was fatigue.
Apalutamide, also known by its research codes ARN-509/JNJ-927, is a second-generation androgen receptor antagonist due to be filed next year. Sales are forecast to reach $1.2bn by 2022, according to EvaluatePharma data, and the asset has an NPV of $5.5bn, 2% of the company’s market cap.
J&J gained apalutamide through its acquisition of Aragon Pharmaceutical in 2013 for $650m up front. Sales of Zytiga are expected to peak at $2.3bn this year but drop to $1.1bn by 2022 after the drug's patent expires in 2017.
|JZP-110||12-wk obstructive sleep apnoea study
6-wk obstructive sleep apnoea study
|Apalutamide||Non-metastatic castration-resistant prostate cancer||NCT01946204 (Spartan)|