What is the tanezumab story?

Adverse effects reported with human anti-NGF monoclonal antibodies

This post is designed to be read with our update on anti-NGF monoclonal antibodies in canine OA.

Link to bedinvetmab pain update

Tanezumab is a monoclonal antibody designed to treat chronic pain, particularly osteoarthritis (OA), by targeting and inhibiting nerve growth factor (NGF). Tanezumab resulted in a condition called Rapidly Progressive Osteoarthritis (RPOA) in people, with an unclear aetiology.

In one of the laboratory trials of bedinvetmab, the authors examined the safety of the product in young adult Beagle dogs (Krautmann et al 2021). The authors state that there are no agreed mitigation strategies addressing concerns that long-term use of anti-NGF mAbs or uncontrolled concurrent self-medication with NSAIDs might increase the incidence of RPOA unacceptably over time. Furthermore, they report that rapidly progressive osteoarthritis has not been recognized in veterinary medicine (not quite true – see below re rat studies).

The Krautmann paper uses Wise et al (2021) as a supporting reference, a narrative review on human subjects entitled ‘The evolution of nerve growth factor inhibition in clinical medicine’.

Wise states;

Clinical studies in individuals with painful knee and hip osteoarthritis have revealed that NGF inhibitors substantially reduce joint pain and improve function compared with NSAIDs for a duration of up to 8 weeks. However, the higher tested doses of NGF inhibitors also increased the risk of rapidly progressive osteoarthritis in a small percentage of those treated. In addition, Anti-NGF antibodies carry an increased risk of adverse events compared with placebo that are primarily of a peripheral neurological nature (Wise et al 2021).

Safety Profile of Anti-NGF Antibodies: Insights from Meta-Analyses & Independent Evaluation

Meta-analyses have reaffirmed the safety outcomes observed in individual studies. Treatment in humans with anti-NGF antibodies was associated with an increased incidence of peripheral neuropathy and sensory-related adverse events and rapidly progessive OA (RPOA) (Wise et al 2021).

Risk Profile and Preclinical Findings Related to Anti-NGF Therapy in Osteoarthritis

Currently, there is no clear understanding of the risk profile for human osteoarthritis (OA) patients who are likely to develop rapidly progressive osteoarthritis (RPOA), and the same can be said for canine or feline patients. While neurological sensory adverse effects associated with anti-NGF therapy are generally reversible upon discontinuation, RPOA is irreversible.

Anti-NGF antibodies carry an increased risk of adverse events compared with placebo that are primarily of a peripheral neurological nature. This is known in the human field. It was not documented in clinical trials in dogs, however ataxia is the third most common AE reported (Monteiro et al 2025). These effects are being seen and reported in clinical practice and should be captured in future adverse event reporting.

Clinical studies in individual human subjects with painful knee and hip osteoarthritis have revealed that NGF inhibitors substantially reduce joint pain and improve function compared with NSAIDs for a duration of up to 8 weeks. However, the higher tested doses of NGF inhibitors also increased the risk of rapidly progressive osteoarthritis in a small percentage of those treated.

Preclinical studies have explored the effects of anti-NGF antibodies, such as tanezumab, in animal models. In one study using a rat model of medial meniscal injury, treatment with tanezumab initiated at the time of injury and continued for 28 days protected animals from gait deficiency. However, animals treated with anti-NGF antibodies (tanezumab) at any dose exhibited increased cartilage damage, subchondral bone sclerosis, and tibial osteophyte formation compared to controls.

In another study using a monosodium iodoacetate-induced OA model, anti-NGF antibody treatment at the time of injury prevented weight-bearing asymmetry but resulted in greater cartilage damage in the treated knee by day 28 compared to vehicle controls. When treatment was delayed until 14 or 21 days post-injury, rats showed reduced weight-bearing asymmetry and mechanical allodynia at day 28, with no significant difference in cartilage damage. Notably, there was a reduction in osteoclast numbers in the tibial plateau of anti-NGF-treated rats compared to saline-treated controls.

These findings confirm that anti-NGF therapies provide effective analgesia and can be beneficial at various stages of OA. However, they also highlight potential risks, including cartilage degeneration, synovitis, and altered osteoclast activity in the subchondral bone. Importantly, joint damage was more pronounced when anti-NGF treatment was initiated during the early stages of disease (LaBranche et al., 2017; Xu et al., 2016).

On balance, it is therefore possible that anti-NGF products could affect normal joint function in dogs and cats.

Assessment of Risk Associated with Anti-NGF Antibodies: Findings from an Independent Expert Committee

To better understand the risks associated with anti-NGF antibodies, an independent committee of experts was convened to adjudicate studies involving tanezumab (Hochberg et al 2016). The committee developed validated definitions for radiographic assessments, including criteria for osteonecrosis, progression of other conditions, and cases where information was deemed insufficient.

The committee concluded that there was no association between total joint replacement (TJR) and the dose of tanezumab monotherapy. The overall TJR rate for tanezumab monotherapy was comparable to both placebo and other comparators. However, when tanezumab was administered in combination with NSAIDs, the TJR rate increased proportionally with the tanezumab dose—reaching two to three times the rate observed with placebo.

The committee also evaluated cases of rapidly progressive osteoarthritis (RPOA), which were classified into two types:

• Type 1: Loss of joint space width >1 mm within one year.

• Type 2: Bone loss or destruction not typically seen in end-stage osteoarthritis, including catastrophic bone failure and joint distraction.

Among RPOA cases, 63% occurred in the index joint and 37% in non-index joints. A dose-response relationship was observed with tanezumab monotherapy:

• 2.5 mg: 0 events per 1,000 patients

• 10 mg: 11 events per 1,000 patients

When tanezumab was combined with NSAIDs, the incidence of RPOA increased significantly compared to comparators. Hazard ratios ranged from:

• 8.6 for 2.5 mg tanezumab + NSAIDs

• 17.5 for 10 mg tanezumab + NSAIDs

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These findings demonstrate a clear dose-response relationship between tanezumab and RPOA, with NSAIDs contributing to an elevated risk.

We should therefore exercise caution with the concurrent use of NSAIDs and anti-NGF products in dogs and cats.

Tanezumab Studies: Persistent Risk of Joint Deterioration at Lower Doses

Data from tanezumab studies show that even when administered at lower doses, the risk of joint deterioration remains elevated, particularly when tanezumab is used in combination with non-steroidal anti-inflammatory drugs (NSAIDs). This highlights that reducing the dose does not eliminate the risk, and that NSAID co-administration may further contribute to joint damage.

Concerns Regarding Long-Term Anti-NGF Therapy and RPOA in Veterinary Medicine

According to Krautmann, no established mitigation strategies currently exist to address concerns that long-term use of anti-NGF monoclonal antibodies (mAbs) or uncontrolled concurrent self-medication with NSAIDs may lead to an unacceptable increase in the incidence of rapidly progressive osteoarthritis (RPOA) over time. Notably Krautmann et al state that RPOA has not yet been recognized within veterinary medicine – although this was 2021 and much has changed since

Reports of possible RPOA in dogs

From the preceeding narrative, peripheral neuropathy (PN) is recognised in the human field. PN was not documented in canine clinical trials (Corral 2021, Michels 2023) although dogs in these studies underwent veterinary exam, not specifically a neurological evaluation. Dogs in the Krautmann study did undergo neurological examination and neurological concerns were not reported as findings. Clinical signs consistent with peripheral neuropathies are being seen and reported in clinical practice and should be captured in adverse event reporting. This will help determine if such findings could be treatment related or are consistent with the background population.

References

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Farrell M, Adams R, von Pfeil DJF. Re: Laboratory safety evaluation of bedinvetmab, a canine anti-nerve growth factor monoclonal antibody, in dogs. Vet J. 2024 Jun;305:106104. doi: 10.1016/j.tvjl.2024.106104. Epub 2024 Apr 3. PMID: 38580157

Farrell M, Waibel FWA, Carrera I, Spattini G, Clark L, Adams RJ, Von Pfeil DJF, De Sousa RJR, Villagrà DB, Amengual-Vila M, Paviotti A, Quinn R, Harper J, Clarke SP, Jordan CJ, Hamilton M, Moores AP, Greene MI. Musculoskeletal adverse events in dogs receiving bedinvetmab (Librela). Front Vet Sci. 2025 May 9;12:1581490. doi: 10.3389/fvets.2025.1581490.

Hochberg, M. C. et al. When is osteonecrosis not osteonecrosis?: Adjudication of reported serious adverse joint events in the tanezumab clinical development program. Arthritis Rheumatol. 68, 382–391 (2016).

Iff I, Hohermuth B, Bass D, Bass M. A case of potential rapidly progressing osteoarthritis in a dog during bedinvetmab treatment. Vet Anaesth Analg. 2025 Mar-Apr;52(2):263-265. doi: 10.1016/j.vaa.2024.11.041.

Krautmann M, Walters R, Cole P, Tena J, Bergeron LM, Messamore J, Mwangi D, Rai S, Dominowski P, Saad K, Zhu Y, Guillot M, Chouinard L. Laboratory safety evaluation of bedinvetmab, a canine anti-nerve growth factor monoclonal antibody, in dogs. Vet J. 2021 Oct;276:105733. doi: 10.1016/j.tvjl.2021.105733.

LaBranche TP, Bendele AM, Omura BC, Gropp KE, Hurst SI, Bagi CM, Cummings TR, Grantham LE 2nd, Shelton DL, Zorbas MA. Nerve growth factor inhibition with tanezumab influences weight-bearing and subsequent cartilage damage in the rat medial meniscal tear model. Ann Rheum Dis. 2017 Jan;76(1):295-302. doi: 10.1136/annrheumdis-2015-208913.

Michels GM, Honsberger NA, Walters RR, Kira S Tena J, Cleaver DM. A prospective, randomized, double-blind, placebo-controlled multisite, parallel-group field study in dogs with osteoarthritis conducted in the United States of America evaluating bedinvetmab, a canine anti-nerve growth factor monoclonal antibody. Vet Anaesth Analg. 2023 Sep;50(5):446-458. doi: 10.1016/j.vaa.2023.06.003.

Monteiro BP, Simon A, Knesl O, Mandello K, Nederveld S, Olby NJ, Innes JF, Lascelles BDX. Global pharmacovigilance reporting of the first monoclonal antibody for canine osteoarthritis: a case study with bedinvetmab (Librela™). Front Vet Sci. 2025 Apr 24;12:1558222. doi: 10.3389/fvets.2025.1558222.

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