Teva/Xenon’s Pain Ointment Failure Leaves Sparser Nav1.7 Pipeline

The Phase IIb failure of Teva Pharmaceutical Industries Ltd./Xenon Pharmaceuticals Inc.’s TV-45070 pain ointment in osteoarthritis is another blow for the once very promising Nav1.7 target, but some consultants advise not to rule the class out yet in other indications.

TV-45070 is a small molecule inhibitor of the sodium channel Nav1.7 and other sodium channels, including those that are expressed in the pain-sensing peripheral nervous system, according to the sponsors. Teva acquired global rights to TV-45070 (XEN-402) from Xenon in a deal worth $41 million up front and regulatory and sales milestones of up to $335 million (Also see "Xenon Feels No Pain After $41M Upfront From Teva" - Pink Sheet, 11 Dec, 2012.). [See Deal]

Teva and Xenon announced July 1 that a topical formulation of TV-45070 failed a primary endpoint in a Phase IIb study, but maintained it did have a good safety and tolerability profile, with no drug-related serious adverse events (see box).

Teva said that the companies will continue to evaluate the trial results but do not plan on further development in osteoarthritis pain.

The partners also noted that development has always included both nociceptive and neuropathic pain and that a Phase IIb study in post-herpetic neuralgia continues, with results due in the second half of 2016, and they stressed that neuropathic pain has a different mechanism to chronic pain and osteoarthritis.

Xenon stock price closed down on July 1 by 17.35% at $9.53 from a close of $11.53 on June 30.

Nav1.7 Misses Again

Pfizer Inc. had been at the forefront of the discovery that people with a certain genetic profile could not sense pain and acquired partner Icagen Inc., a specialist in ion channel pain drugs, to develop the concept (Also see "Pfizer Looks To Buy Icagen To Fold Into Neusentis Pain Research Unit" - Pink Sheet, 20 Jul, 2011.).

Nav1.7 had been a “highly anticipated mechanism” so the Teva/Xenon news is disappointing, NI Research’s Harry Tracy, a consultant specializing in neuroscience drug development, commented in an interview.

But the space has a history of failure. The discontinuation of development of TV-45070 in osteoarthritis pain leaves a sparse Nav1.7 pipeline. Pfizer has suspended development of three drugs aimed at the target for inflammatory pain. A fourth drug – PF-05089771 – remains in development for diabetic neuropathic pain, having been suspended for post-surgical pain in 2012 and chronic pain in February. Biogen Idec’s CNV1014802 is in Phase II for neuropathic pain and sciatica.

The failure of TV-45070 does not completely eliminate the possibility that a different drug in the class might have benefit for inflammatory pain, but the news is obviously not encouraging, Tracy said. The fact that TV-45070 didn’t work in inflammatory disease doesn’t rule out neuropathic pain, as the diseases are very different, he added.