A positive hit in a phase III tardive dyskinesia trial positions Neurocrine Biosciences’ valbenazine for a head-to-head battle against Teva’s Austedo.
However, both agents are basically variations on an existing theme – Valeant/Lundbeck’s Xenazine – which happens to have lost patent protection two months ago. Given the scarcity of central nervous system disorder successes it would be unfair to detract from Neurocrine’s achievement but, with drug pricing coming under scrutiny, me-too products might increasingly be frowned on.
This consideration, of course, is purely theoretical, since no mechanism exists in the US for payers to negotiate lower prices on account of a drug’s lack of novelty. But the issue is a live one, given that the whole industry is fighting a public relations battle to prove that investing in novel R&D justifies high drug costs.
So just how novel are Austedo and valbenazine relative to Xenazine? Austedo is a deuterated version of Xenazine’s active ingredient, tetrabenazine, while valbenazine is a tetrabenazine metabolite; all three inhibit VMAT2, which is involved in dopamine transport.
One way for Teva and Neurocrine to differentiate themselves would be to demonstrate safety advantages over Xenazine, which has a known side effect of depression. For now there are only hints of an advantage, and certainly no data are available to distinguish between the Teva and Neurocrine agents on a safety basis.
In the phase III Kinect 3 trial valbenazine (NBI-98854) showed a statistically significant advantage in terms of the abnormal involuntary movements scale (AIMS) for both its 80mg dose, which Neurocrine said was considered for the primary endpoint, and 40mg, which was not – on both a per-protocol and intent-to-treat basis (p<0.0001 for all).
The Kinetic 3 data are solid, notwithstanding that, after a process of eliminating the stumbling blocks Neurocrine had encountered in phase II, the odds of phase III success had been stacked in its favour (Upcoming events: Late-stage data on CNS drugs from Neurocrine and KemPharm, July 10, 2015).
For its part Teva earlier reported a numerically lower but still significant AIMS benefit for Austedo, though across-study comparisons are notoriously unreliable; valbenazine was dosed over six weeks on a fixed basis, while Austedo had had a 12-week course in which it was titrated up.
Of course both agents were compared with placebo and not head to head versus Xenazine; that would have risked giving an answer that neither company would have liked. Teva and Neurocrine want Xenazine-like efficacy at much lower doses, which on an across-trial basis they seem to have done, Xenazine being titrated up to 100mg per day.
Neurocrine said it would file valbenazine in the US next year, and Leerink analysts said a safety signal in an ongoing open-label trial represented the only residual risk. Teva recently filed Austedo for Huntington’s chorea, and in tardive dyskinesia it is awaiting data from the AIM-TD fixed-dosing study.
|Austedo||ARM-TD||-1.4-point AIMS difference vs placebo, titrated up to 48mg (12wk)||NCT02195700|
|Austedo||AIM-TD||200 patients, fixed dosing||NCT02291861|
|Valbenazine||Kinect 3||-3.1-point AIMS difference vs placebo for 80mg dose (6wk)||NCT02274558|
|Valbenazine||Kinect 4||150 patients, safety & tolerability||NCT02405091|
In valbenazine Neurocrine has an unpartnered asset with positive phase III data, so it must be seen as ripe for takeover – with Lundbeck or Valeant as obvious interested parties. However, after yesterday’s 12% stock increase the group is valued at $3.7bn – a hefty amount, especially considering that the consensus-based NPV of valbenazine is $1.3bn, assuming 100% launch probability.
Teva had acquired Austedo through a $3.2bn takeover of Auspex, but that was back in March, before the recent pricing storm upset the biopharma bull market. Auspex now looks to have been expensive, and future buyers will undoubtedly be more careful.