Bedinvetmab: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Bedinvetmab, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Librela™ (NADA/ANADA 141-562)
Librela™ NADA 141-562, Original approval, May 05, 2023; sponsor Zoetis Inc.; species: Dogs; foi_id 13959; FDA PDF
Indication
Control of pain associated with osteoarthritis in dogs.
Dose regimen
0.23 mg/lb (0.5 mg/kg) minimum, dosed by weight band (whole vials), subcutaneous injection, once a month, effectiveness established when given as a minimum of two doses one month apart
The dose of Librela™ (bedinvetmab) is 0.23 mg bedinvetmab/lb (0.5 mg bedinvetmab/kg) body weight, administered subcutaneously once a month.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| tmax | 7 days | SC, 1-10 mg/kg every 28 days, 6-month laboratory safety study in Beagles (serum, ligand binding assay) | The time to reach maximum concentration (Tmax) was 7 days. |
| half-life | 8.8 days to 10.0 days (elimination T1/2) | SC, 1-10 mg/kg every 28 days, 6-month laboratory safety study | The elimination half-life (T1/2) ranged from 8.8 days to 10.0 days. |
| other | Cmax and AUC0-28d approximately dose-proportional on Day 0 and Day 140; similar in both sexes | SC, 1, 3, 10 mg/kg every 28 days | Toxicokinetic exposure [maximum observed concentration (Cmax) and area under the serum concentration-time curve from time zero to 28 days (AUC0-28d)] on Day 0 (1st dose) and Day 140 (6th dose) increased approximately in proportion to the bedinvetmab dose and exposures were similar in both sexes. |
| other | slight accumulation by Day 140; steady state after approximately 2 doses | SC every 28 days, 6-month laboratory safety study | There was slight accumulation on Day 140 compared to Day 0 and steady-state was achieved after approximately 2 doses. |
Target-animal safety
dose multiples 0X (0 mg/kg), 1X (1 mg/kg), 3X (3 mg/kg), 10X (10 mg/kg); duration 7 SC doses every 28 days (Days 0-168), necropsy 2 weeks after last dose (~6 months); animals 8 dogs per group (4 per sex) in 4 groups.
Experimental Design: Dogs were randomly allocated to one of 4 treatment groups of 8 dogs per group (4 per sex). Dogs were administered Librela™ or a negative control (saline) every 28 days for 7 doses.
| Finding | Quote |
|---|---|
| Scabbing on face, neck and thorax in all groups except 1 mg/kg | Scabbing on the face, neck, and thorax was seen across all groups except the 1 mg/kg group. |
| Injection site redness: 1 control, 2 at 1 mg/kg, 5 at 3 mg/kg, 5 at 10 mg/kg | Injection site redness was noted sporadically for 1 dog in the control group, 2 dogs in the 1 mg/kg treatment group, 5 dogs in the 3 mg/kg treatment group, and 5 dogs in the 10 mg/kg treatment group. |
| Decreased albumin in 1 and 3 mg/kg groups (within reference range) | Compared to the control group, decreased albumin was observed in dogs in the 1 mg/kg treatment group and 3 mg/kg treatment group. |
| Cartilage necrosis/erosion of the ulnae in one 1 mg/kg dog | One dog in the 1 mg/kg treatment group with focal proteoglycan depletion had mild focal cartilage necrosis in the left ulna and an erosion in the cartilage and degeneration of the right ulna. |
| Conclusion: scabbing lesions of head/neck associated with bedinvetmab; boney changes possibly treatment-related | Scabbing lesions of the head and neck are associated with bedinvetmab. The boney changes may be progression of an underlying musculoskeletal condition; however, a potential relation to treatment cannot be ruled out. |
Effectiveness
Two multi-center, double-masked, randomized, placebo (saline)-controlled field studies: US Study C161C-US-17-178 (272 dogs; 135 Librela, 137 control) and EU Study C866C-XC-17-194 (287 dogs; 141 Librela, 146 control); Librela 0.5 mg/kg SC on Days 0, 28 and 56; weight-of-evidence approach; primary endpoint: Treatment success on Day 28 by owner CBPI (reduction >= 1 in Pain Severity Score and >= 2 in Pain Interference Score vs baseline); result: Day 28 success: US 48% Librela vs 36.1% control (not significant, P = 0.0719); EU 45.2% vs 17.0% (significant, P = 0.0018); success rates higher than control from Day 42 onward in both studies
While the studies had similar success rates on Day 28 in the treatment groups administered Librela™ (48% and 45.2%), the studies had differences in the success rates in the control groups. The success rate in the control group in the US study was 36.1% and the success rate of the control group in the EU study was 17.0%. Based on these results, there was a larger treatment effect size in the EU study as compared to the US study. The US study did not demonstrate a significant difference in treatment success at the pre-specified primary endpoint (Day 28), while the EU study demonstrated a significant difference in treatment effect at Day 28.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Urinary tract infection (US study) | 15/135 (11.1%) | 11/137 (8.0%) | Librela™ n (%) (Total N = 135) Negative Control n (%) (Total N = 137) Urinary tract infection 15 (11.1) 11 (8.0) Bacterial skin infection 11 (8.1) 9 (6.6) Dermatitis 10 (7.4) 8 (5.8) Dermal mass 8 (5.9) 5 (3.6) Erythema 6 (4.4) 5 (3.6) Dermal cyst(s) 4 (3.0) 2 (1.5) Pain on injection 4 (3.0) 2 (1.5) Inappropriate urination** 4 (3.0) 1 (0.7) Histiocytoma 3 (2.2) 0 (0.0) |
| Bacterial skin infection (US study) | 11/135 (8.1%) | 9/137 (6.6%) | Librela™ n (%) (Total N = 135) Negative Control n (%) (Total N = 137) Urinary tract infection 15 (11.1) 11 (8.0) Bacterial skin infection 11 (8.1) 9 (6.6) Dermatitis 10 (7.4) 8 (5.8) Dermal mass 8 (5.9) 5 (3.6) Erythema 6 (4.4) 5 (3.6) Dermal cyst(s) 4 (3.0) 2 (1.5) Pain on injection 4 (3.0) 2 (1.5) Inappropriate urination** 4 (3.0) 1 (0.7) Histiocytoma 3 (2.2) 0 (0.0) |
| Dermatitis (US study) | 10/135 (7.4%) | 8/137 (5.8%) | Librela™ n (%) (Total N = 135) Negative Control n (%) (Total N = 137) Urinary tract infection 15 (11.1) 11 (8.0) Bacterial skin infection 11 (8.1) 9 (6.6) Dermatitis 10 (7.4) 8 (5.8) Dermal mass 8 (5.9) 5 (3.6) Erythema 6 (4.4) 5 (3.6) Dermal cyst(s) 4 (3.0) 2 (1.5) Pain on injection 4 (3.0) 2 (1.5) Inappropriate urination** 4 (3.0) 1 (0.7) Histiocytoma 3 (2.2) 0 (0.0) |
| Pain on injection (US study) | 4/135 (3.0%) | 2/137 (1.5%) | Librela™ n (%) (Total N = 135) Negative Control n (%) (Total N = 137) Urinary tract infection 15 (11.1) 11 (8.0) Bacterial skin infection 11 (8.1) 9 (6.6) Dermatitis 10 (7.4) 8 (5.8) Dermal mass 8 (5.9) 5 (3.6) Erythema 6 (4.4) 5 (3.6) Dermal cyst(s) 4 (3.0) 2 (1.5) Pain on injection 4 (3.0) 2 (1.5) Inappropriate urination** 4 (3.0) 1 (0.7) Histiocytoma 3 (2.2) 0 (0.0) |
| Increased blood urea nitrogen (EU study) | 19/138 (13.8%) | 7/143 (4.9%) | Librela™ n (%) (Total N = 138) Negative Control n (%) (Total N = 143) Increased Blood Urea Nitrogen (BUN)** 19 (13.8) 7 (4.9) Lethargy 5 (3.6) 0 (0.0) Emesis 4 (2.9) 1 (0.7) |
| Lethargy (EU study) | 5/138 (3.6%) | 0/143 (0.0%) | Librela™ n (%) (Total N = 138) Negative Control n (%) (Total N = 143) Increased Blood Urea Nitrogen (BUN)** 19 (13.8) 7 (4.9) Lethargy 5 (3.6) 0 (0.0) Emesis 4 (2.9) 1 (0.7) |
Extraction notes: Effectiveness n_dogs left null because no single contiguous sentence contains both the enrolled/evaluated counts and the result; enrolled numbers are given in the design string (US 272, EU 287). PK values are toxicokinetics from the 6-month margin-of-safety study (no Cmax/AUC numeric values are printed). TAS total of 32 dogs is stated elsewhere ('Thirty-two (16 male, 16 female)') but n_animals is expressed per group to match the design quote. Adverse reactions taken from Table II.5 (US) and Table II.9 (EU); both tables survived PDF extraction.
Reproduce: foi_structured_search(query="Bedinvetmab") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).