Upcoming events: Late-stage data on CNS drugs from Neurocrine and KemPharm

Welcome to your weekly digest of approaching regulatory and clinical readouts. Neurocrine Biosciences will reveal top-line data from its phase III trial of tardive dyskinesia drug NBI-98854 in the second half of 2015. There are no FDA-approved drugs to treat the movement disorder and those used off-label have side-effects; if it succeeds in the trial the candidate faces an open goal.

KemPharm also expects phase III data, in its case from a trial assessing the abuse liability of its fast-acting painkiller KP201. The opioid will have little chance of approval unless it can show itself abuse-resistant – but if it can, the company will be an excellent prospect for a takeover.

Only Kinect

The neurological disorder tardive dyskinesia causes involuntary repetitive movements and is hard or even impossible to treat. It is often the result of long-term or high-dose use of antipsychotic drugs, or, in children and infants, as a side-effect of drugs for gastrointestinal disorders.

A vesicular monoamine transporter 2 (VMAT2) inhibitor, NBI-98854 is intended to regulate the levels of dopamine released during nerve communication, while having minimal impact on other monoamines. This selectivity ought to reduce the likelihood of “off-target” side-effects, Neurocrine says. ‘98854 has breakthrough designation.

The placebo-controlled Kinect 3 study is testing the ability of two doses of  NBI-98854 – 40mg and 80mg – to improve tardive dyskinesia symptoms. It is 90% powered to show a two point improvement from baseline on the abnormal involuntary movements scale (AIMS).

Neurocrine has been clever with its trial design. The first phase II trial of the drug, Kinect 1, failed; its primary endpoint, AIMS score, was assessed by the trial investigators and results varied. In its second phase II study videos of the patients were rated separately, delivering more consistent results and a hit on the endpoint. When the company did a reanalysis of Kinect 1 using video assessment, even that trial was successful.

Not surprisingly, Neurocrine has opted for video assessment in Kinect 3. And the trial is covered by a special protocol agreement with the FDA, so if the endpoint is hit, there is a high likelihood of approval.

If it is approved, NBI-98854 could have a market opportunity of $500m in tardive dyskinesia, according to analysts from Deutsche Bank. EvaluatePharma’s consensus forecasts model 2020 sales of $395m.

Likeable?

US lawmakers have put increasing emphasis on reducing the abuse of opioid painkillers over the past few years. KemPharm must therefore prove that its immediate-release pill of hydrocodone and acetaminophen, KP201, cannot be exploited by addicts if it is to gain US approval.

KP201 has already demonstrated the bioequivalence to branded hydrocodone – Norco – required for approval, so the only remaining hurdles are the oral and intranasal abuse liability studies that are expected to report later this quarter.

The painkiller is designed in such a way that the drug’s effect will only kick in after it is digested in the gastrointestinal tract. According to analysts at Cowen and Company, KemPharm has “one of the most sophisticated and elegant abuse-deterrent approaches” in its ligand activated therapy platform technology.

This involves attaching one or more molecules to the drug to create prodrugs. Tackling abuse at the molecular level contrasts with other abuse-deterrent technologies, which tend to involve combining the opioid with another drug or using an abuse-deterrent capsule or physical matrix.

The current clinical trials are designed to measure the “likability” of KP201, compared with Norco, either when taken orally at levels greater than the recommended dosage or inhaled after having been ground into a powder.

If the trials have positive results, KP201 could be approved next year, launched in early 2017 and by 2025 capture a 7-8% share of immediate-release hydrocodone/APAP prescriptions, Cowen analysts believe. This would translate into $500m in US sales.

If the trials hit and approval arrives on schedule, there is a reasonable chance that one of the larger pain or CNS-focused drug companies might swoop on Neurocrine. KemPharm floated on the Nasdaq in April rather successfully thanks to excitement around KP201. The best case for shareholders is that the drug achieves its potential by becoming the first abuse-deterrent immediate-release hydrocodone to reach the US.

To contact the writer of this story email Elizabeth Cairns in London at [email protected] or follow @LizEPVantage on Twitter