Librela: A Canine Osteoarthritis Drug Approved Without Proven Effectiveness
How did an ineffective drug for osteoarthritis in pets get FDA approval?
The approval of a drug that ultimately proves ineffective can raise significant concerns, especially when it involves the health and well-being of our beloved pets.
Just like human medications, veterinary drugs must pass through rigorous testing and evaluation before receiving FDA approval. This includes clinical trials designed to assess safety and effectiveness in target animal populations.
Or do they?
I previously wrote about the recently approved monoclonal antibody therapy, Librela (bedinvetmab), for treatment of osteoarthritis in dogs (Solensia for cats).
This particular drug has been touted for its effectiveness in 2 clinical studies conducted in the US and European Union (EU) with a total of 559 dogs for reducing pain associated with osteoarthritis (OA).
The graphs on the professional website are misleading regarding the efficacy of Librela.
This graph for the US field study is from the Librela (bedinvetmab) website under the “Efficacy” section. There is also a graph from the European clinical study on the website.
Source: https://www.librelavetteam.com/
Each graph presents the “% Success Rate Measured by CBPI” for both the Librela-treated group and a placebo group at various timepoints (7, 14, 28, 42, 56, and 84 days post treatment). According to the graphs on the website, a p-value 0.05 was marked on Days 42, 56, and 84 in the US field study and on Days 7, 14, 28, 42, 56 and 84 in the EU field study. A p-value is generally understood in the scientific community to indicate statistical significance if it is less than 0.05.
**Canine Brief Pain Inventory (CBPI), an owner-completed questionnaire designed to quantify the severity of OA pain and the impact of that pain on the activity of dogs.
The drug showed no significant difference as compared to placebo at the 28 day primary effectiveness study endpoint in the US field study.
Not only that but data on the graphs is false and misleading in that it erroneously concludes an effect at later time points when in fact there is no effect due to statistical Type I error. When multiple endpoints are tested statistically, the Type I error rate may be inflated.
This can be a difficult concept to understand. This video attempts to explain in simple terms what a Type 1 error is in statistics.
The bottom line is a Type 1 error is considered a false positive. This means that it is the probability of erroneously concluding an effect when the truth is that there is no effect. In this case this statistics wrongly concluded that the drug was more effective in reducing OA pain than the placebo when in fact there was no difference at any time point.
Neither the US nor the EU study was designed to make statistical conclusions regarding effectiveness at study days other than the primary endpoint on day 28. Adjustments were not made in the study to account for the potential inflation of Type I error rate, leading to false interpretation of effectiveness of the drug at later time points.
Therefore, the inclusion of a p-value (i.e., p 0.05) on the graphs on the website for the secondary time points creates a misleading impression about the efficacy of Librela, undermining the ability of the reader to understand the study results presented.
The Librela website was found to be in violation of the Federal Food, Drug and Cosmetic Act (FD&C Act).
The FDA notified Zoetis, the company that produces Librela, on November 20, 2023 that the Librela website makes false and misleading claims and representations about the efficacy of Librela.
Source: https://www.fda.gov/media/174818/download
I am not aware of any response by Zoetis to this letter from the FDA. Clearly, the website has not been updated or changed to reflect the concerns outlined by the FDA in this letter.
The ADUFA authorizes the FDA to collect fees for certain animal drug applications.
Congress first passed and signed into law the Animal Drug User Fee Act (ADUFA) in 2003. It has since been reauthorized in 2008, 2013, 2018 and 2023.
This act, similar to PDUFA for human drugs, authorizes the FDA to collect fees for certain animal drug applications and supplements, products, establishments, and sponsors of animal drug applications and/or investigational animal drug submissions. These fees are used to fund more expedient approval of drugs.
Source: https://www.fda.gov/animal-veterinary/cvm-updates/fda-announces-fy-2025-animal-drug-user-fee-rates-adufa-and-agdufa
This allows the pharmaceutical industry to exert significant influence on the drug development and approval processes. Companies may push for approvals based on limited data, hoping that post-market surveillance will reveal more about a drug's effectiveness.
For 2023, the year Librela was approved for use, the revenue from sponsor fees were approximated to be 27 percent of total fee revenue for the FDA. The target revenue amounts for each fee category for FY 2023, were as follows: for application fees, the target revenue amount was $6,428,800; for product fees, the target revenue amount was $8,678,880; for establishment fees, the target revenue amount was $8,357,440 and for sponsor fees, the target revenue amount was $8,678,880.
The Animal Drug User Fee Act (ADUFA) base fee revenue for fiscal year (FY) 2023 was $29,931,240.
How can an agency regulate an industry that is paying much of its operating expenses? I have previously written about regulatory capture and how this is a serious conflict of interest.
Please share this letter to help educate veterinary professionals about Librela.
What can you do? Please print and share this letter so we can help educate veterinary professionals about the dangers of this antibody therapy.
