Verdinexor: what the FDA reviewed for dog products
2 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Verdinexor, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- LAVERDIA® (NADA/ANADA 141-614)
LAVERDIA® NADA 141-614, Original approval, December 18, 2025; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 17795; FDA PDF
Indication
Treatment of lymphoma in dogs.
Dose regimen
Initial 1.25 mg/kg; if tolerated after 2 weeks increase to 1.5 mg/kg; reductions of 0.25 mg/kg to a minimum of 1 mg/kg for adverse reactions, Oral (coated tablets: 2.5, 10, 22.5, 50 mg), Twice per week with at least 72 hours between doses, Feed the dog immediately before dosing; wear chemotherapy-resistant gloves; do not split or crush tablets; provide Client Information Sheet
a) Administer LAVERDIA® at an initial dose of 1.25 mg/kg administered orally twice per week (e.g., Monday and Thursday or Tuesday and Friday) with at least 72 hours between doses. b) If tolerated after 2 weeks, increase the dose of LAVERDIA® to 1.5 mg/kg twice per week with at least 72 hours between doses. c) Dose reductions of 0.25 mg/kg to a minimum dose of 1 mg/kg twice per week with at least 72 hours between doses or dose interruptions may be considered if the dog has adverse reactions (see ANIMAL SAFETY WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS).
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| half-life | approximately 4 to 6 hours (plasma) | Dogs; stated in the user-safety section citing published literature (Sadowski et al., 2018) | The plasma half-life of verdinexor in dogs is approximately 4 to 6 hours, and within 60 hours, the drug typically undergoes 10 half-lives of elimination and less than 0.09% of the initial dose is present. |
| bioavailability | three- to five-fold greater in fed than in fasted dogs | Food effect; basis for feeding immediately before dosing | The bioavailability of verdinexor in fed dogs is three- to five-fold greater than in fasted dogs. |
Target-animal safety
dose multiples Sham (0 mg/kg), 1.0 mg/kg, 1.5 mg/kg, 1.75 mg/kg (1.17X the maximum intended clinical dose); duration 13 weeks, 3 times weekly (Monday/Wednesday/Friday), fed before dosing; GLP (Study No. ANIV-126b-901); animals Thirty-two Beagles (sixteen male and 16 female); four groups of eight (four males, four females).
Study Animals: Sixteen male and 16 female Beagle dogs were selected. The dogs were approximately 7 months old at the initiation of dose administration. Body weights ranged from 7.1 kg to 10.8 kg for the males and 4.9 kg to 7.2 kg for the females at the initiation of dosing. Experimental Design: This was a masked, randomized, sham (untreated) controlled laboratory study. The thirty-two dogs were randomly assigned to four treatment groups of eight dogs each (four males and four females).
| Finding | Quote |
|---|---|
| All dogs survived to scheduled necropsy | All animals survived to the scheduled necropsy. |
| Dose-dependent drug-related findings: vomiting, inappetence, decreased body condition and body weight, loss of skin elasticity, lacrimation; non-dose-dependent: abnormal feces, excessive shedding, sparse hair | Dose-dependent LAVERDIA®-related findings included vomiting, inappetence, decreased body condition, decreased body weight, loss of skin elasticity, and lacrimation. Non-dose-dependent LAVERDIA®-related findings included abnormal feces (soft, watery, or mucoid feces), excessive shedding, and sparse hair. |
| Weight loss over the study in 1 sham, 7 (1.0 mg/kg), 8 (1.5 mg/kg) and 4 (1.75 mg/kg) dogs | Individually, 1 dog in the sham control, 7 dogs in the 1.0 mg/kg group, 8 dogs in the 1.5 mg/kg group, and 4 dogs in the 1.75 mg/kg group lost weight during the study (i.e., weighed less on study Day 91 compared to study Day -1). |
| Neurobehavioral: slight depression in 2 dogs at 1.75 mg/kg; slight decrease of forelimb strength in 2 dogs (1.5 and 1.75 mg/kg) on Day 89 | On study Day 89, slight depression was observed in 2 dogs administered 1.75 mg/kg LAVERDIA® and slight decrease of forelimb strength was observed in 2 dogs, 1 dog administered 1.5 mg/kg and 1 dog administered 1.75 mg/kg LAVERDIA®. |
| Clinical pathology: lower lymphocytes, eosinophils, monocytes and chloride; higher fibrinogen, albumin and BUN | Clinical pathology findings related to the administration of LAVERDIA® included decreases in lymphocytes, eosinophils, monocytes, and chloride; and increases in fibrinogen, albumin, and blood urea nitrogen. |
| Lower testes, thymus and thyroid/parathyroid weights; dose-dependent testicular/epididymal degeneration and thymic lymphoid depletion in all treated groups | Dose-dependent microscopic findings were present in the testes and epididymides (moderate to marked degeneration/atrophy in the seminiferous tubules; minimal to moderate vacuolation, and minimal Leydig cell hypertrophy in the testes; and severe oligospermia/germ cell debris in the epididymides) in males in all LAVERDIA® treatment groups, and in the thymus (minimal to mild cortical lymphoid depletion) in all LAVERDIA® treatment groups. |
| No drug-related effects on heart rate, respiration, body temperature, blood pressure, ophthalmoscopy or urinalysis | There were no LAVERDIA®-related effects on heart rate, respiration, or body temperature. |
Effectiveness
Pivotal multi-center (10 US sites), prospective, randomized (4:1), masked, placebo-controlled 56-day field study (No. ANIV-126b-401; 2022-2025) in dogs with naive or first-relapse B- or T-cell lymphoma (Stage II-IV); 160 enrolled (127 LAVERDIA, 33 control) evaluable for safety; LAVERDIA 1.25 mg/kg twice weekly increased to 1.5 mg/kg after 2 weeks if tolerated; GCP; n = 134 evaluable for effectiveness; primary endpoint: Time to progression (TTP): days from Day 0 to progressive disease of target or non-target lesions (modified VCOG response criteria); result: Median TTP 37 days (95% CI 29-57) with LAVERDIA vs 23 days (95% CI 14-30) with control; statistically significant treatment effect (p=0.011). 31 dogs (29.2%) in the LAVERDIA group vs 2 (7.1%) controls completed the 56-day study. Effectiveness population: 106 LAVERDIA, 28 control.
Results: Time to progression or last follow-up was calculated for the 134 evaluable cases. The estimated median TTP was 37 days in the LAVERDIA® group (with a 95% confidence interval of 29 to 57 days) and 23 days in the control group (with a 95% confidence interval of 14 to 30 days). There was a statistically significant effect of treatment group (p-value = 0.011) for TTP of dogs treated with LAVERDIA® compared to control group.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Anorexia (field study; LAVERDIA n=127, control n=33) | 94 (74.0%) | 17 (51.5%) | Anorexia* 94 74.0% 17 51.5% |
| Emesis | 78 (61.4%) | 12 (36.4%) | Emesis 78 61.4% 12 36.4% |
| Weight loss | 66 (52.0%) | 4 (12.1%) | Weight loss 66 52.0% 4 12.1% |
| Diarrhea | 54 (42.5%) | 11 (33.3%) | Diarrhea 54 42.5% 11 33.3% |
| Elevated serum alkaline phosphatase (ALP) | 29 (22.8%) | 2 (6.1%) | Elevated serum alkaline phosphatase (ALP) 29 22.8% 2 6.1% |
| Serious adverse events | 28/127 (22%) | 5/33 (15.2%) | Serious adverse events (SAEs) were reported in 22% (28 of 127) of the dogs in the LAVERDIA® group and 15.2% (5 of the 33) of the dogs in the control group. |
Extraction notes: Original NADA. Adverse-reaction rows are quoted as flattened Table II.3 rows: term, LAVERDIA n, %, control n, %. Lethargy was 78 (61.4%) vs 18 (54.5%); elevated ALT 28 (22.0%) vs 3 (9.1%). Twenty-two LAVERDIA dogs and four control dogs died or were euthanized during the field study. Table II.2 (disease progression by study day) is a flattened table not extracted. PK values come from the user-safety section (literature); the pilot studies (KS-50, KARYO-1, KARYO-2) established a maximum tolerated dose of 1.75 mg/kg twice weekly. Target-animal-safety dose multiples are expressed by the summary as mg/kg 3 times weekly, with 1.75 mg/kg described as 1.17X the maximum intended clinical dose.
LAVERDIA® NADA 141-614, Original approval, January 11, 2021; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 18233; FDA PDF
Indication
Treatment of lymphoma in dogs (conditional approval)
Dose regimen
1.25 mg/kg initial; increase to 1.5 mg/kg after 2 weeks if tolerated; reductions of 0.25 mg/kg to a minimum of 1 mg/kg, Oral (coated tablets), fed immediately before dosing, Twice per week with at least 72 hours between doses, Continuous; dose interruptions for adverse reactions; do not split or crush tablets; chemotherapy-resistant gloves for handling
Administer LAVERDIA™ -CA1 at an initial dose of 1.25 mg/kg administered orally twice per week (e.g., Monday and Thursday or Tuesday and Friday) with at least 72 hours between doses (see Table 1). 4. If tolerated after 2 weeks, increase the dose of LAVERDIA™ -CA1 to 1.5 mg/kg twice per week with at least 72 hours between doses (see Table 2). 5. Dose reductions of 0.25 mg/kg to a minimum dose of 1 mg/kg twice per week with at least 72 hours between doses (see Table 3) or dose interruptions may be considered as a result of adverse reactions (see ANIMAL SAFETY WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS).
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| half-life | approximately 4 to 6 hours | Dogs (user-safety section citing Sadowski et al. 2018) | The plasma half-life of verdinexor in dogs is approximately 4 to 6 hours, and within 60 hours, the drug typically undergoes 10 half-lives of elimination and less than 0.09% of the initial dose is present. |
| other | Less than 0.09% of initial dose present within 60 hours (10 half-lives) | Dogs, plasma | The plasma half-life of verdinexor in dogs is approximately 4 to 6 hours, and within 60 hours, the drug typically undergoes 10 half-lives of elimination and less than 0.09% of the initial dose is present. |
| tmax | 5.3 hours post-dose (average) | 8 dogs with lymphoma, 1.25 or 1.5 mg/kg, fed, Mon/Wed/Fri dosing, Day 14 (one dog Day 21), field study KARYO-2 | For all dogs, the average Tmax occurred at 5.3 hours post-dose, with a T1/2 of 5 hours, regardless of dose. |
| half-life | 5 hours | 8 dogs with lymphoma, 1.25 or 1.5 mg/kg, fed, regardless of dose | For all dogs, the average Tmax occurred at 5.3 hours post-dose, with a T1/2 of 5 hours, regardless of dose. |
| tmax | 1.1 hours (healthy research dogs) vs 5.3 hours (dogs with lymphoma) | Healthy research dogs vs lymphoma field-study dogs; AUC similar | Although the Tmax for dogs with lymphoma occurred several hours later than did that observed in healthy research dogs (5.3 versus 1.1 hours respectively), the AUC values tended to be similar in both healthy and dogs with lymphoma. |
| bioavailability | 3- to 5-fold greater in fed than fasted dogs | Fed vs fasted | The bioavailability of verdinexor in fed dogs is 3- to 5-fold greater than in fasted dogs. |
| other | Mean Cmax and AUC at 1.5 mg/kg slightly higher than at 1.25 mg/kg (no numeric values given) | 8 dogs with lymphoma, fed | The mean Cmax and AUC for dogs receiving 1.5 mg/kg were slightly higher than that of dogs receiving 1.25 mg/kg. |
Target-animal safety
dose multiples 0 (sham), 1.0 mg/kg 3x/week (0.67X), 1.5 mg/kg 3x/week (1X maximum intended clinical dose), 1.75 mg/kg 3x/week (1.17X); duration 13 weeks, 3 times weekly (Mon/Wed/Fri), fed before dosing; animals Sixteen male and 16 female.
This study was conducted to evaluate the safety of LAVERDIA™ -CA1 (verdinexor tablets), when administered orally at up to 1.17X (1.75 mg/kg) the maximum intended clinical dose 3 times weekly for 13 weeks to healthy Beagle dogs. Study Animals: Sixteen male and 16 female Beagle dogs were selected.
| Finding | Quote |
|---|---|
| Adequate margin of safety at label regimen | The study demonstrated that LAVERDIA™ -CA1 has an adequate margin of safety for the treatment of lymphoma when administered at an initial dose of 1.25 mg/kg administered orally twice per week with at least 72 hours between doses, with an increase to 1.5 mg/kg after two weeks. |
| All animals survived to scheduled necropsy | All animals survived to the scheduled necropsy. |
| Dose-dependent: vomiting, inappetence, decreased body condition and body weight (also loss of skin elasticity, lacrimation) | Dose-dependent LAVERDIA™ -CA1-related findings included vomiting, inappetence, decreased body condition, decreased body weight |
| Non-dose-dependent: abnormal feces, excessive shedding, sparse hair | Non-dose-dependent LAVERDIA™ -CA1-related findings included abnormal feces (soft, watery, or mucoid feces), excessive shedding, and sparse hair. |
| Clinical pathology: decreased lymphocytes, eosinophils, monocytes, chloride; increased fibrinogen, albumin, BUN | Clinical pathology findings related to the administration of LAVERDIA™- CA1 included decreases in lymphocytes, eosinophils, monocytes, and chloride; and increases in fibrinogen, albumin, and blood urea nitrogen. |
| Lower testes, thymus and thyroid/parathyroid weights with testicular, epididymal and thymic histologic lesions | Compared to sham control dogs, there were lower mean testes weights (absolute and relative to body and brain weights) in males in all LAVERDIA™ -CA1 treatment groups, lower mean thymus weights (absolute and relative to body and brain weights) in the 1.5 mg/kg and 1.75 mg/kg groups, and lower thyroid/parathyroid gland weights (absolute and relative to body and brain weights) in all LAVERDIA™ -CA1 treatment groups. |
| No effects on heart rate, respiration or body temperature | There were no LAVERDIA™ -CA1 related effects on heart rate, respiration, or body temperature. |
Effectiveness
Conditional approval (reasonable expectation of effectiveness): exploratory open-label, single-arm, multicenter (10 sites) field study KARYO-2 in dogs with naive (35) or first-relapse (23) lymphoma, non-commercial formulation, three dosing regimens (1.5 mg/kg 3x/wk, 1.25 mg/kg 3x/wk, or 1.25 then 1.5 mg/kg 2x/wk); not randomized, not masked; n = 58; primary endpoint: Exploratory: time to progression (TTP), objective response rate (ORR), duration of response, disease control rate at 8 weeks (VCOG criteria); result: Median TTP 29.5 days (n=50; range 7-244); ORR 34.5% (20/58; 1 CR, 19 PR); DCR at 8 weeks 29% (17/58)
Results: Reasonable Expectation of Effectiveness: Effectiveness was evaluated in 58 dogs. TTP was evaluated in 50 dogs (8 dogs were removed from the study prior to progression). For the 50 dogs, median TTP was 29.5 days (range 7 - 244 days). The median TTP for the naïve (30/50 dogs) and first relapse (20/50 dogs) cases were 36.5 days (range 7 - 244 days) and 22 days (range 7 - 194 days), respectively. The ORR for all dogs was 34.5% (20/58 dogs; 1 CR and 19 PRs), distributed proportionately between the naïve (12/35 dogs, 34.3%) and first relapse (8/23 dogs, 34.8%) subgroups.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Anorexia | 43 dogs (grade 1: 26, grade 2: 14, grade 3: 3) | Adverse Reaction Number of Dogs Gradesa 1 2 3 4 5 Anorexia 43 26 14 3 - - Vomiting 34 28 6 - - - Diarrhea 30 20 10 - - - Weight loss 28 18 9 1 - - Lethargy 24 21 3 - - - Polydipsia 19 17 2 - - - | |
| Vomiting | 34 dogs (grade 1: 28, grade 2: 6) | Adverse Reaction Number of Dogs Gradesa 1 2 3 4 5 Anorexia 43 26 14 3 - - Vomiting 34 28 6 - - - Diarrhea 30 20 10 - - - Weight loss 28 18 9 1 - - Lethargy 24 21 3 - - - Polydipsia 19 17 2 - - - | |
| Diarrhea | 30 dogs (grade 1: 20, grade 2: 10) | Adverse Reaction Number of Dogs Gradesa 1 2 3 4 5 Anorexia 43 26 14 3 - - Vomiting 34 28 6 - - - Diarrhea 30 20 10 - - - Weight loss 28 18 9 1 - - Lethargy 24 21 3 - - - Polydipsia 19 17 2 - - - | |
| Weight loss | 28 dogs (grade 1: 18, grade 2: 9, grade 3: 1) | Adverse Reaction Number of Dogs Gradesa 1 2 3 4 5 Anorexia 43 26 14 3 - - Vomiting 34 28 6 - - - Diarrhea 30 20 10 - - - Weight loss 28 18 9 1 - - Lethargy 24 21 3 - - - Polydipsia 19 17 2 - - - | |
| Lethargy | 24 dogs (grade 1: 21, grade 2: 3) | Adverse Reaction Number of Dogs Gradesa 1 2 3 4 5 Anorexia 43 26 14 3 - - Vomiting 34 28 6 - - - Diarrhea 30 20 10 - - - Weight loss 28 18 9 1 - - Lethargy 24 21 3 - - - Polydipsia 19 17 2 - - - | |
| Polydipsia | 19 dogs (grade 1: 17, grade 2: 2) | Adverse Reaction Number of Dogs Gradesa 1 2 3 4 5 Anorexia 43 26 14 3 - - Vomiting 34 28 6 - - - Diarrhea 30 20 10 - - - Weight loss 28 18 9 1 - - Lethargy 24 21 3 - - - Polydipsia 19 17 2 - - - |
Extraction notes: Conditional approval (CA1); the summary text is headed 'Conditional Approval Application 141-526' while the catalogue metadata lists application_number 141-614, which is retained here. Effectiveness is a single-arm exploratory study (no control), so adverse reaction counts are numbers of dogs out of 58 treated with no control column ('58' is not in the table quote). The TAS study dosed 3x weekly (more frequent than the 2x weekly label regimen); 1.75 mg/kg = 1.17X the maximum intended clinical dose of 1.5 mg/kg. The '™' in product name normalizes to 'TM' in the validator.
Reproduce: foi_structured_search(query="Verdinexor") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).