Therapy Focus - Pain Pipeline Comes Under Pressure

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Includes: BIIB, ENDP, LLY, NVS, PFE, REGN, TEVA
by: EP Vantage

The FDA is desperate for non-opioid painkillers, and it shows. Fast-track designation for Pfizer (NYSE:PFE) and Lilly's (NYSE:LLY) 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 (NYSE:NVS) and Biogen (NASDAQ:BIIB) 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 (NASDAQ:ENDP) 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.

Sparse

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
Phase III
Tanezumab Anti-NGF MAb Pfizer/Eli Lilly NME Injection
Fasinumab Anti-NGF MAb Teva/Regeneron/Mitsubishi Tanabe NME Injection
Phase II
BIIB074 (raxatrigine) NaV 1.7 sodium channel blocker Biogen NME Oral
CNTX-4975 (capsaicin) TRPV 1 agonist Centrexion Therapeutics NDA Injection
EMA401 AT2 antagonist Novartis NME Oral
VVZ-149 GlyT2 inhibitor, 5-HT2A & P2X3 antagonist Vivozon NDA Injection
Source: EvaluatePharma.

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 skeptical 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 (NVS) 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 program 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
NCT02609828 Cancer pain
NCT02697773 Osteoarthritis
NCT02709486 Osteoarthritis
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
NCT02844725 Post-operative

But with its checkered 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 (NYSE:TEVA) and Regeneron (NASDAQ:REGN) 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.

Getting hotter

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.