The FDA is desperate for non-opioid painkillers, and it shows. Fast-track designation for Pfizer and Lilly’s tanezumab might speed up the availability of a new option, but the history of the anti-nerve growth factor agent means its safety will be under scrutiny.
A lack of other late-stage candidates should help Lilly and Pfizer’s cause, but even if tanezumab succeeds the monoclonal antibody will be expensive and likely reserved for chronic, intractable pain. Oral projects from Novartis and Biogen could hold more promise for routine use, but these are at an earlier stage of development (see table below).
Perhaps more companies will move into the space if the FDA continues to clamp down on opioid developers – a direction it could be heading in after asking Endo International last week to withdraw its opioid painkiller Opana ER, which had been specifically designed to make it less prone to abuse (FDA’s move could mean Endo suffers from opioid withdrawal, June 9, 2017).
Other supposedly abuse-deterrent opioids could be put under further pressure at an FDA meeting scheduled for July 10-11.
For now, though, the late-stage pipeline for novel, non-narcotic pain medicines is sparse, the analysis below reveals. The list was sourced from EvaluatePharma and has been filtered to exclude the many projects that do not appear to be in active development. The analysis focuses on projects being tested in joint pain, cancer-induced pain, forms of neuralgia or post-operative pain.
|The non-narcotic pain pipeline|
|Product||Pharma class||Companies||Proprietary level||Route of admin|
|Tanezumab||Anti-NGF MAb||Pfizer/Eli Lilly||NME||Injection|
|Fasinumab||Anti-NGF MAb||Teva/Regeneron/Mitsubishi Tanabe||NME||Injection|
|BIIB074 (raxatrigine)||NaV 1.7 sodium channel blocker||Biogen||NME||Oral|
|CNTX-4975 (capsaicin)||TRPV 1 agonist||Centrexion Therapeutics||NDA||Injection|
|VVZ-149||GlyT2 inhibitor, 5-HT2A & P2X3 antagonist||Vivozon||NDA||Injection|
Projects in earlier-stage development worth watching include Biogen’s BIIB074, which is in a large phase II study, Relay, in patients with a form of neuropathic pain. Relay should yield data late this year or early next.
However, failure in a phase IIb trial in trigeminal neuralgia has left analysts sceptical about the project’s chances. This does not seem to have put Biogen off; a phase III trial in this indication is listed on clinicaltrials.gov but has not yet begun recruiting patients.
Meanwhile, Novartis has filed to start a phase II study of its AT2 antagonist EMA401 in post-herpatic neuralgia – the project was acquired with its 2015 acquisition of the Australian drug developer Spinifex. And Vivozon is currently conducting two phase II studies of its agent in post-operative pain settings, with data due later this year or early next.
Tanezumab is well of ahead these projects: its phase III programme includes six trials, five of which are set to complete next year.
|Trials to watch|
|Project||Company/ies||Key trials||Lead indication||Next event|
|Tanezumab||Pfizer/Lilly||NCT02528188||Osteoarthritis||PhIII data 2018|
|NCT02528253 (Tango)||Chronic lower back pain|
|Fasinumab||Teva/ Regneron||NCT02683239 (Fact LTS & OA)||Osteoarthritis||PhIII data 2018|
|NCT03161093 (Fact OA1)||Osteoarthritis|
|BIIB074||Biogen||NCT02935608 (Relay-1)||Neuropathic pain||PhII data late '17/early '18|
|NCT03070132||Trigeminal neuralgia||PhIII data 2020|
|EMA401||Novartis||NCT03094195 (Emphene)||Post-herpatic neuralgia||PhII data H2 2018|
|VVZ-149||Vivozon||NCT02992041||Post-operative||PhII data late '17/early '18|
But with its chequered past, success for tanezumab is far from certain. The project – along with the entire anti-NGF class – was put on clinical hold in 2011 after reports of osteonecrosis, and work on tanezumab only restarted in 2015.
Teva and Regeneron also have an anti-NGF MAb in development, fasinumab, but with only two phase III trials ongoing they appear to be making a more tentative bet on the space.
Also vying for a place with another novel mechanism is Centrexion Therapeutics, which will present new six-month data with its capsaicin-based candidate CNTX-4975 at the Eular meeting tomorrow.
The company had previously reported that the phase IIb Triumph study in chronic knee osteoarthritis met its primary endpoint, a reduction in the pain with walking WOMAC score at 12 weeks (Centrexion still has work to do after pain Triumph, December 14, 2016).
More detailed results confirm what was suspected at the time – the 1mg dose, but not the 0.5mg dose, hit significance. This benefit with the higher dose was sustained over six months. CNTX-4975 was given as single injection into the knee at the start of the study.
Centrexion plans to start a phase III trial of CNTX-4975 later this year and it seems likely that the 1mg dose will be the one it takes forward.
The US opioid crisis means there could be big rewards for whoever succeeds in bringing an alternative painkiller to the market. But with the inherent risks associated with pain projects, maybe it is no wonder that the non-opioid pipeline is so bare.