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Adverse Reactions to LIBRELA

I normally do not get involved in looking at pharmaceuticals since that is the realm of western veterinary medicine. But friends have asked me about Librela and I’ve found myself repeating the information I shared and so I’ve compiled just a few sources of information to get you started in your own research.

Most of the studies quotes in the references are for humans since that is where the bulk of the research is, but the information about the drug is from Zoetis and I did find a database tracking adverse reactions for dogs in Europe.

What is LIBRELA?

It is an injectible solution containing 5, 10, 15, 20, or 30 mg/mL of bedinvetmab in 20 mM histidine buffer pH 5.0 [(0.027% w/v L-histidine and 0.382% w/v histidine HCl monohydrate), 8.5% w/v trehalose dihydrate, 0.005% w/v disodium EDTA dihydrate, 0.01% w/v L-methionine, and 0.1% w/v poloxamer 188]. Bedinvetmab is a canine IgG monoclonal antibody (mAb), in which the variable regions from canine B cell sequence were joined with canine IgG constant sequences, and is expressed through recombinant DNA techniques in Chinese hamster ovary (CHO) cells. Bedinvetmab binds to nerve
growth factor (NGF) to reduce NGF’s effects. Such mAbs are commonly referred to as anti-NGF mAbs.

When was LIBRELA approved by the FDA?

March 2023 in the United States and 2020 in Europe.

Who Does Zoetis Say This Is Indicated For?

LIBRELA is indicated for the control of pain associated with osteoarthritis in dogs.

Why Are Dog Owners Drawn To It?

They don’t want to see their dogs in pain when they walk and they want them to be pain free.

What Has Zoetis Shared About It?

The safety of LIBRELA was assessed in a masked, controlled 84-day US field study evaluating the effectiveness of LIBRELA for the control of pain associated with osteoarthritis. Enrollment included 272 dogs, 135 dogs treated with LIBRELA and 137 dogs treated with a negative control (sterile saline). The enrolled dogs were at least 1 year of age (1 to 17 years old), weighed between 1.8 to 62.7 kg and were of various breeds or non-purebred. Dogs were dosed at 28-day intervals and received up to three injections. The most common adverse reactions reported during the study are summarized in Table 2 below.

One dog in the LIBRELA group was diagnosed with pyelonephritis on Day 15; this dog had pre-existing increased serum BUN and creatinine and a recent history of urinary tract infection that was not confirmed resolved prior to enrollment. Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen were initiated on Day 7 for osteoarthritis-associated joint pain but NSAIDs were discontinued on Day 10 due to anorexia and gastroenteritis; azotemia worsened at Day 13 and the dog received no further LIBRELA treatment.

One dog in the LIBRELA group with a history of atopy, developed mild alopecia and mild erythema on the injection site on Days 5 and 23. Both episodes of alopecia and erythema resolved with treatment.

A total of 89 dogs were enrolled in a 6-month, single arm, open labeled, uncontrolled continuation of the EU field study and received monthly subcutaneous injections of LIBRELA. The study provided additional field safety information.

One dog experienced acute gastroenteritis and recovered following treatment for abdominal pain, fever, vomiting, and anorexia. One large breed dog enrolled for stifle osteoarthritis developed acute forelimb lameness that was diagnosed as elbow dysplasia. Two dogs presented with rear limb paresis of unknown etiology, one of whom responded to ongoing NSAID treatment and one who did not.

This can be found on Zoetis’s website: HERE

Are There Any Adverse Reports Being Tracked?

Only in Europe. We don’t have this information accessible to us here in the United States. I took this information from this WEBSITE. Look up Veterinary, and then the drug Librela (April 2, 2024).

About Nerve Growth Factors

There continues to be an unmet need for safe and effective pain medications.

Nerve growth factor (NGF) is a signaling molecule produced by cells in the body that plays a critical role in the nervous system. It is essential for the development, survival, and function of certain neurons, particularly sensory and sympathetic neurons.

  • It’s present in various cells through out the body and it targets tissues like muscles and glands.
  • It binds to receptors of developing neuroans.
  • It sends a cascade of signals inside neurons.
  • It is not limited to juse the nervous system, it is also involved in the development and functin of other cell types such as immune cells.
  • It is involved in pain which is why it’s a target for the development of pain medications.

The discovery of nerve growth factor (NGF) and its interaction with tropomyosin receptor kinase A (trkA) have been well characterized as important mediators of pain initiation and maintenance, and pharmacotherapies targeting this pathway have the potential to be considered promising methods in the treatment of a variety of nociceptive and neuropathic pain conditions. Several methodologic approaches, including sequestration of free NGF, prevention of NGF binding and trkA activation, and inhibition of trkA function, have been investigated in the development of new pharmacotherapies. Among these, NGF-sequestering antibodies have exhibited the most promise in clinical trials. However, in 2010, reports of rapid joint destruction leading to joint replacement prompted the US Food and Drug Administration (FDA) to place a hold on all clinical trials involving anti-NGF antibodies. Although the FDA has since lifted this hold and a number of new trials are under way, the long-term efficacy and safety profile of anti-NGF antibodies are yet to be established.

NGF background

NGF was initially discovered in the 1950s as a tumor tissue-produced soluble factor that promotes the growth and differentiation of sensory and sympathetic ganglia.7,8 NGF was the first growth factor to be identified and its discovery represented a landmark achievement in developmental neurobiology. The illumination of NGF’s critical role in neuronal development eventually led to the creation of the “neurotrophic factor hypothesis” and the classical neurotrophic model in which NGF is synthesized and released by target tissues during embryonic development, promoting the growth, differentiation, and survival of neurons in a dose-dependent manner.7,9 Subsequent studies have broadened our understanding of this process and the role that neurotrophic factors play in the mammalian nervous system.7,8

NGF belongs to a family of neurotrophic factors or neurotrophins comprising brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Neurotrophins act by binding to two types of cell surface receptors: neurotrophin receptor (NGFR or p75) and a family of tyrosine kinase receptors, tropomyosin-related kinase A (trkA), trkB, and trkC. All neurotrophins bind NGFR/p75 with similar affinity, but each neurotrophin binds preferentially to a specific trk receptor; NGF preferentially binds trkA, BDNF binds trkB, and NT-3 binds trkC.10 TrkA is highly expressed by sensory neurons of the dorsal root ganglia (DRG) during embryogenesis; however, by the postnatal period, trkA expression and NGF sensitivity decline, and the role of NGF–trkA signaling shifts from promoting neuron growth and survival to regulating the sensitivity of the peripheral nervous system to noxious stimuli.11

Talk To Your Vet About Side Effects

If your dog is in pain and your vet is recommending this product, ask them to:

  • Explain how this will work for your dog
  • Explain the side effects that may present itself
  • Read the Zoetis’s published data on their studies (tables source linked above)
  • Ask your vet if there are other options

Each dog is unique and it’s outside of my scope to guide you on veterinary care. I share this information for you to have some sources to get you started so that you may conduct your own research and have a conversation with your vet.

Seek Second Opinions

There are more options than just injectibles. Diet and herbs can help. If you’re unsure and need a second opinion, call around and ask another vet.

For a holistic approach with Chinese Herbs you can consult with my vet:

Dr. Dennis Thomas

Holistic Health Care for Pets
1707 E. 11th Ave, Spokane WA 99202
Call: 509-214-2676

If you would like to contact him via email: DrThomasHolisticvet@yahoo.com

I use him for my own dogs, and refer clients to him when a TCVM vet isn’t available in your city.

In Closing

I recognize that seeing your dog in pain is excruciatingly difficult. With all of the choices out there it can get confusing. Be sure to do your research and weigh the costs vs. benefits and advocate for your dog’s health.

Wishing you and your dogs, good health!

References

1. Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain. 2012;13(8):715–724. [PubMed] [Google Scholar]

2. Kissin I. The development of new analgesics over the past 50 years: a lack of real breakthrough drugs. Anesth Analg. 2010;110(3):780–789. [PubMed] [Google Scholar]

3. Woolf CJ, Max MB. Mechanism-based pain diagnosis: issues for analgesic drug development. Anesthesiology. 2001;95(1):241–249. [PubMed] [Google Scholar]

4. Cohen SP, Mao J. Neuropathic pain: mechanisms and their clinical implications. BMJ. 2014;348:f7656. [PubMed] [Google Scholar]

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7. Aloe L. Rita Levi-Montalcini: the discovery of nerve growth factor and modern neurobiology. Trends Cell Biol. 2004;14(7):395–399. [PubMed] [Google Scholar]

8. Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: from the early discoveries to potential clinical use. J Transl Med. 2012;10:239. [PMC free article] [PubMed] [Google Scholar]

9. Yuen EC, Howe CL, Li Y, Holtzman DM, Mobley WC. Nerve growth factor and the neurotrophic factor hypothesis. Brain Dev. 1996;18(5):362–368. [PubMed] [Google Scholar]

10. Hefti FF, Rosenthal A, Walicke PA, et al. Novel class of pain drugs based on antagonism of NGF. Trends Pharmacol Sci. 2006;27(2):85–91. [PubMed] [Google Scholar]

11. Bennett DLH. Neurotrophic factors: important regulators of nociceptive function. Neuroscientist. 2001;7(1):13–17. [PubMed] [Google Scholar]

12. Chang DS, Hsu E, Hottinger DG, Cohen SP. Anti-nerve growth factor in pain management: current evidence. J Pain Res. 2016 Jun 8;9:373-83. doi: 10.2147/JPR.S89061. PMID: 27354823; PMCID: PMC4908933. [PubMed]

13. Corral, Maria J., Moyaert, Hilde et al. A prospective randomized, blinded, placebo controlled multisite clinical study of bedinvetmab, a canine monoclonal antibody targeting nerve growth factor, in dogs with osteoarthritis. A Veterinary Anaesthesia and Analgesia, 2021

Author Biography

Hannah Zulueta obtained her Certificate in Canine Nutrition from CASI Institute. She is also studying for her Doctorate in Acupuncture, Traditional Chinese Medicine, and Herbalism from the esteemed Pacific College of Health and Medicine.

She resides in San Diego with her three dogs, Maggie, Orbit, and Mr. Higgins.

She is available for one on one consultations. Additionally, you can find her sharing free content on Instagram.

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