Table 2.

Adverse Reactions Reported in the Field Study1

Solensia Vehicle Control
Adverse Reaction
N=182 (%) N=93 (%)
Vomiting 24 (13.2%) 10 (10.8%)
77 mg/mL Injection site pain2 20 (10.9%) 13 (14%)
Diarrhea 12 (6.6%) 5 (5.4%)
Feline anti-nerve growth factor monoclonal antibody for subcutaneous injection in cats only.
Abnormal behavior and behavioral disorders3 12 (6.6%)4 5 (5.4%)5
Single-Use Vial
Renal insufficiency6 12 (6.6%) 4 (4.3%)
CAUTION Anorexia 12 (6.6%) 4 (4.3%)
Federal law restricts this drug to use by or on the order of a licensed veterinarian. Lethargy 11 (6.0%) 3 (3.2%)
DESCRIPTION Dermatitis 11 (6.0%) 1 (1.1%)
SOLENSIA (frunevetmab injection) is a sterile injectable solution containing 7mg/mL of frunevetmab Alopecia 10 (5.5%) 2 (2.2%)
in histidine buffer (10 mM L-histidine monohydrochloride, 5% D-sorbitol, 0.01%polysorbate 20, Dehydration 8 (4.4%) 0 (0.0%)
adjusted to pH 6.0 by HCl/NaOH, quantity sufficient to 1 mL by Water for Injection.). Frunevetmab is Lameness7 8 (4.4%) 2 (2.2%)
a felinized immunoglobulin G monoclonal antibody (mAb), a murine antibody in which all regions of
the mouse antibody are replaced with feline counterparts except for the complementarity-determining Pruritus 7 (3.8%) 0 (0.0%)
regions. Frunevetmab binds to nerve growth factor (NGF) to block NGF’s effects. Such mAbs are Weight loss 6 (3.3%) 5 (5.4%)
commonly referred to as anti-NGF mAbs. Scabbing on head/neck 6 (3.3%) 1 (1.1%)
Gingival disorder 5 (2.7%) 0 (0.0%)
INDICATION
SOLENSIA is indicated for the control of pain associated with osteoarthritis in cats. Bacterial skin infection 4 (2.2%) 1 (1.1%)
Otitis externa 4 (2.2%) 0 (0.0%)
DOSAGE AND ADMINISTRATION
Cats should be dosed by weight range according to the Dosing Chart (Table 1) below. Cats are given
1
If a cat experienced the same event more than once, only the first occurrence is reported
2
The control product was the vehicle without active ingredient
the full content of 1 or 2 vials based on body weight to target a minimum dosage of 0.45 mg/lb. 3
Behavior abnormal for the individual cat
(1 mg/kg) body weight, administered subcutaneously once a month. Aseptically withdraw the total 4
Individual cats had at least one of the following behavior changes: anxiety (1), hiding (1),
dose into a single syringe and administer immediately. hypersomnia (1), inappropriate urination (5), sleeping with owner (1), vocalization (3),
The product does not contain a preservative. The full content of each vial is for single use only. increased aggressive behavior (1)
Once punctured, contents of the vial should be used immediately and any remaining solution should 5
Individual cats had at least one of the following behavior changes: anxiety (2),
be discarded. disorientation (1), inappropriate urination (2), and vocalization (1)
6
Worsening of existing disease
Table 1. Dosing Chart 7
New lameness or worsening of previous lameness
Weight of Cat Weight of Cat Number of
Volume The safety of SOLENSIA was also evaluated in a masked, controlled 56-day exploratory field study to
(lb.) (kg) Vials*
evaluate the effectiveness of SOLENSIA for the control of pain associated with osteoarthritis in cats.
5.5‑15.4 2.5‑7 kg 1 mL 1
Enrollment included 126 cats; 85 cats were treated with frunevetmab injection manufactured similar to
15.5‑30.8 7.1‑14 kg 2 mL 2 SOLENSIA and 41 cats were administered a vehicle control. Cats were dosed at 28-day intervals and
*1 mL frunevetmab injection per vial received up to two injections. The most frequently reported adverse reactions were digestive tract
disorders, including vomiting and diarrhea, and skin disorders, including dermatitis/eczema and
CONTRAINDICATIONS alopecia that were mostly attributed to irritation by an activity monitor collar required for the study.
SOLENSIA should not be administered to cats with known hypersensitivity to frunevetmab.
SOLENSIA should not be used in breeding cats or in pregnant or lactating queens because it may
Immunogenicity 05 Aug 2021 15:38
All therapeutic proteins, including monoclonal antibodies, have the potential for immunogenicity,
pass through the placental blood barrier and be excreted in milk. Fetal abnormalities, increased rates including the production of antibodies that bind to the therapeutic protein and may decrease
of stillbirths and increased postpartum fetal mortality were noted in rodents and primates receiving effectiveness. Such host-derived antibodies are termed anti‑drug antibodies (ADA). SOLENSIA,
anti‑NGF mAbs. therefore has the potential to cause the cat to produce ADAs against frunevetmab.
WARNINGS The presence of binding antibodies to frunevetmab in cats was assessed using a screening and
User SafetyWarnings confirmatory assay approach. In controlled field effectiveness studies in cats with osteoarthritis
Not for use in humans. Keep out of reach of children. (see EFFECTIVENESS), four out of 259 cats that received SOLENSIA once monthly developed
Hypersensitivity reactions, including anaphylaxis, could potentially occur in the case of accidental anti‑drug antibodies (ADAs). One cat tested positive for ADAs on Days 0, 28, 56, and 84. This cat
self-injection. had non-detectable plasma drug concentration levels of SOLENSIA on Days 28 and 56, and was a
treatment failure in the effectiveness analysis, suggesting that the ADAs may have clinical significance.
In case of accidental self-injection, seek medical advice immediately and show the package leaflet or
No assessment for neutralizing antibodies was performed.
the label to the physician.
The observed incidence of antibody positivity in an assay is highly dependent on several factors
Pregnant women, women trying to conceive, and breastfeeding women should take extreme care to
including assay sensitivity and specificity, assay methodology, sample handling, timing of sample
avoid accidental self-injection.
collection, concomitant medications, and underlying disease. For these reasons, comparison of the
The importance of NGF in ensuring normal fetal nervous system development is well-established and incidence of antibodies to SOLENSIA with the incidence of antibodies to other products may not
laboratory studies conducted on nonhuman primates with human anti‑NGF antibodies have shown be appropriate.
evidence of reproductive and developmental toxicity.
CONTACT INFORMATION
PRECAUTIONS To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety
Administration of mAbs may be associated with hypersensitivity reactions and delayed hypersensitivity Data Sheet (SDS), contact Zoetis Inc. at 1-888‑963-8471.
reactions. If anaphylaxis or other hypersensitivity reaction occurs, discontinue use and institute
For additional information about reporting adverse drug experiences for animal drugs, contact
appropriate therapy.
FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae.
Administration of SOLENSIA may be associated with scabbing on the head and neck, dermatitis, and
pruritus; however, pre-approval data suggest that these signs do not require cessation of SOLENSIA CLINICAL PHARMACOLOGY
administration (see ADVERSE REACTIONS and TARGET ANIMAL SAFETY). Mechanism of Action
Evaluations were not made to determine if interactions occurred between SOLENSIA and Frunevetmab is a felinized monoclonal antibody that binds to nerve growth factor (NGF), reduces
veterinary vaccines. NGF binding to the tropomyosin receptor kinase A (TrkA) and p75NTR receptors, and decreases
signal transduction in cell types involved in pain. In vitro binding studies suggest that frunevetmab
Treatment with SOLENSIA may result in the formation of anti-frunevetmab antibodies and potentially binds with high affinity to NGF, but does not bind to other neurotrophins, including human
the loss of product effectiveness (see Immunogenicity). neurotrophin-3 (NT-3), feline and human neurotrophin-4 (NT-4), and human brain-derived
The safe use of SOLENSIA with concurrent non-steroidal anti-inflammatory drugs (NSAIDs) has not neurotrophic factor (BDNF).
been established in cats. In human clinical trials, rapidly progressing osteoarthritis (RPOA) has been NGF has been found to be elevated in osteoarthritic joints of multiple species. Following a noxious
reported in a small number of patients receiving humanized anti‑NGF mAb therapy. The incidence of stimulus, inflammatory cytokines and NGF are released by tissues of the joint. NGF binds to
these events increased in human patients receiving NSAID treatment long term in combination with TrkA/p75NTR receptors found on peripheral nerves, immune cells, endothelial cells, synoviocytes,
an anti‑NGF mAb. RPOA has not been characterized or reported in cats. and chondrocytes to induce peripheral sensitization, neurogenic inflammation, and increased
SOLENSIA has not been evaluated in cats less than 7 months or 5.5 lbs. pain perception.
Long term effects, which may occur more than 6 months after the use of SOLENSIA, have not been Frunevetmab binds to NGF and prevents NGF/TrkA/p75NTR cellular signaling. In in vitro studies,
evaluated. Primates receiving high doses of anti-NGF mAbs had reduced cell size in postganglionic frunevetmab potently inhibits NGF-mediated signaling as measured by reducing proliferation of
neuronal cell bodies. The change in cell body size returned to normal after anti-NGF mAb administration TF-1 cells, a human erythroleukemia cell line, and functionally blocks NGF-induced neurite outgrowth
was discontinued. NGF is involved in the normal development of sensory and sympathetic nerve in rat PC-12 neuronal cells.
fibers in developing animals. This may be important with use of SOLENSIA in young growing cats. NGF binds to TrkA receptors located on immune cells to elicit the release of additional proinflammatory
The safe use of this product with other mAbs has not been evaluated. mediators, including NGF itself. These inflammatory mediators lead to further peripheral sensitization
involved in pain perception. Frunevetmab reduces the expression of these inflammatory mediators in
ADVERSE REACTIONS
rat PC-12 neuronal cells.
The safety of SOLENSIA was evaluated in a masked, controlled 112‑day field study to evaluate the
effectiveness of SOLENSIA for the control of pain associated with osteoarthritis in cats. Enrollment Pharmacokinetics
included 275 cats weighing 2.5‑to 11.4 kg and 1.6‑to 22.4 years old; 182 cats were treated with In a laboratory safety study in healthy cats administered SOLENSIA (frunevetmab injection)
SOLENSIA and 93 cats were administered a vehicle control. Cats were dosed at 28‑day intervals and subcutaneously once every twenty‑eight days for six consecutive doses (2.8 mg/kg), area under the
received up to three injections. The most common adverse reactions reported during the field study plasma concentration time curve from time zero to the end of the dose interval (AUC) and maximum
are presented below. plasma concentration (Cmax) increased in a less than dose proportional manner. Dosing every 28 days
resulted in minimal accumulation over the course of five consecutive SOLENSIA doses of 2.8 mg/kg.
Table 3. Mean ± Standard Deviation frunevetmab pharmacokinetic parameters Table 7. Percent CSOM Success by Assessment Day
following subcutaneous dosing to laboratory and osteoarthritic cats.
Study Day Solensia (%) Vehicle Control (%)
Parameter Laboratory Cats Osteoarthritic Cats
28 66.9 51.6
Dose (mg/kg) 2.8 3.0
56 75.1 64.8
Cmax (μg/mL) 42.8 ± 10.4 30.2 ± 5.5
Tmax# (day) 3.5 (1‑7) 7.0 (3‑7) 84 76.5 67.3
AUC (day*μg/mL) 596 ± 245 653.0 ± 132 Table 8. Percent Owner Global Assessment Success by Assessment Day
t1/2 (day) 9.8 ± 3.1 11.0 ± 2.5
Bioavailability (%) Not determined 73.2 ± 14.8 Study Day Solensia (%) Vehicle Control (%)
# 28 39.3 30.4
Median and range
56 59.3 48.3
In a cross‑study comparison of the pharmacokinetics in healthy laboratory cats and cats with naturally 84 64.6 57.8
occurring osteoarthritis, the median time to maximum concentration (Tmax) was approximately
3.5 days longer in cats with osteoarthritis compared to healthy cats. Cmax was greater in healthy
cats compared to cats with osteoarthritis. Overall drug exposure (AUC) and half‑life were similar Table 9. Mean Veterinarian-Assessed Total Orthopedic Pain Score by Assessment Day
between healthy cats and cats with osteoarthritis. Compared to an intravenous dose, subcutaneously- Solensia Vehicle Control
administered frunevetmab had a bioavailability of approximately 73% in cats with osteoarthritis. Study Day
(change from baseline) (change from baseline)
In a field effectiveness study at the label dose in cats with osteoarthritis, steady‑state was achieved Screening 34.11 33.6
after approximately 2 doses.
28 28.68 (-5.43) 29.1 (-4.5)
EFFECTIVENESS
Because of the limitations currently inherent in studies designed to assess chronic pain and the 56 27.52 (-6.59) 28.67 (-4.93)
response to drugs intended to control chronic pain in cats, a weight of evidence approach was 84 27.29 (-6.82) 28.54 (-5.06)
employed to determine if the overall evidence supported the conclusion that SOLENSIA was effective
for the control of pain associated with osteoarthritis in cats. Based on current thinking, the endpoints
used to evaluate the effectiveness of SOLENSIA for the control of osteoarthritic pain in cats are TARGET ANIMAL SAFETY
observer-reported measures conducted by either owners or veterinarians. When taken together, the Frunevetmab injection was administered subcutaneously to healthy seven to eight‑month-old cats
results of the two studies described below demonstrate the effectiveness of SOLENSIA for the control (8 cats per group) at doses of 2.8 mg/kg (1X), 8.4 mg/kg (3X), and 14 mg/kg (5X) every 28 days for
of pain associated with osteoarthritis in cats. Additional information related to the evaluation of these six consecutive doses. The control group (8 cats) received vehicle control injections. No clinically
studies, including the study endpoints, is available in the Freedom of Information Summary available significant changes related to frunevetmab were observed among the cats for physical examination,
at https://animaldrugsatfda.fda.gov. lameness evaluation, and body weight.
The most common findings included vomiting and diarrhea observed sporadically in all groups.
Field Effectiveness Study #1 The highest frequency of vomiting occurred in the 1X group. Clinically relevant skin findings included
A 56‑day, masked, randomized, controlled field study was conducted at 14 U.S. veterinary clinics. abrasions, alopecia, or scabs mostly around the face and ears. These findings were noted in three
The study enrolled 126 client‑owned cats with clinical signs of osteoarthritis (OA) confirmed by 1X cats, three 3X cats, and one 5X cat. Another 1X cat developed a 2 cm ventral neck lesion following
radiography and orthopedic examination; enrolled cats weighed 3.3 to 10.5 kg and were over clipping and blood collection on Day 87. Although the initial irritation appeared related to the clipping,
6 months old. The enrolled cats were randomized to treatment with frunevetmab injection (n=85) the unexpectedly severe and persistent pruritus and prolonged recovery were deemed possibly
manufactured similar to SOLENSIA or vehicle control (n=41), administered subcutaneously on
drug-related. The ulcerated skin lesion healed when self‑trauma was prevented including the
Days 0 and 28 or intravenously on Day 0 and subcutaneously on Day 28. Cats were dosed with
placement of an e‑collar for the remainder of the study.
frunevetmab injection or vehicle control based on body weight (2.5‑7 kg cats received 1 mL,
7.1‑14 kg cats received 2 mL). Flinching was occasionally associated with injections, most frequently noted during the first dosing
in all dosing groups. Occasionally, scabs, small abrasions, or spot of alopecia were observed at the
Outcome measures for the control of pain associated with OA included comparison of the owner’s
evaluation of Client Specific Outcomes Measures (CSOM) at Days 14, 28, 42, and 56 compared to injection sites in all dosing groups. A few cats had transient swelling at injection sites.
baseline (Day 0, before treatment); Owner Global Assessments on Days 28 and 56; and total Body tremors and shivering were noted in one 3X cat on Day 28.
orthopedic pain score completed by the veterinarian at screening and on Days 28 and 56. For the Serum creatinine values in females were significantly higher in the 5X group compared to controls
CSOM, treatment success was defined as a reduction of at least 2 in the total CSOM score compared (P < 0.10). Creatinine values on Day 28 were significantly higher (P= 0.0239) in the 1X group
with the score at baseline. Cats that had an increase in any individual CSOM activity score (regardless compared to the control group. On Day 112, values were significantly higher (P = 0.0443) in the
of the total CSOM score) were considered treatment failures. For the Owner Global Assessment, 5X group compared to the control group. Creatinine values did not exceed the reference ranges in
success was defined as an owner’s impression of the response to treatment as Good or Excellent cats of either sex at any time point.
(versus Fair or Poor). Success was not defined for the veterinarian-assessed total orthopedic pain
There was one 1X cat with mild focal discoloration of the left tibiofemoral joint cruciate ligament on
score. The proportion of cats considered treatment successes based on the owner CSOM assessment
gross pathology. There was no correlative pathology on microscopic examination. No lameness was
and the Owner Global Assessment was greater in the frunevetmab injection group compared to the
control group for all assessments. The mean total orthopedic pain score was lower in the frunevetmab reported in this cat or any cat over the course of this study.
injection group compared to the control group at all post‑dosing assessments. One 1X cat had a small amount of bilirubinuria on Day 43. This cat had dark urine and hematuria on
Days 43‑45 with no evidence of UTI on urinalysis. The cat responded to a canned prescription urinary
Table 4. Percent CSOM Success by Assessment Day diet and recovered. This cat also vomited food, bile or hair on three days and had diarrhea or dark,
Study Day Frunevetmab Injection (%) Vehicle Control (%) tarry stools on two days. Another 3X cat had a small amount of bilirubinuria on Day 83 and orange
colored urine. This cat also had elevated serum lactate dehydrogenase activity at three time points.
14 61.8 60.6
There was one 5X cat that had a small amount of bilirubinuria at the end of the study with lipid
28 68.6 55.9
sediment. This cat also had focal hepatic lipidosis on histopathology.
42 73.5 55.9
56 80.0 47.1 STORAGE CONDITIONS
SOLENSIA should be stored upright in a refrigerator, between 35°– 46°F (2°– 8°C). Do not freeze.
Protect from light. See in-use instructions provided in the DOSAGE AND ADMINISTRATION section.
Table 5. Percent Owner Global Assessment Success by Assessment Day
HOW SUPPLIED
Study Day Frunevetmab Injection (%) Vehicle Control (%) SOLENSIA is supplied as a sterile buffered solution of 7mg/mL of frunevetmab in single‑use 4 mL
28 63.2 26.3 glass vials containing an extractable volume of 1mL of clear solution with a butyl rubber stopper and
56 71.1 32.4 aluminum overseal. Vials are available in cartons containing 2 or 6 vials.

Table 6. Mean Veterinarian-Assessed Total Orthopedic Pain Score by Assessment Day Approved by FDA under NADA # 141-546
Frunevetmab Injection Vehicle Control
Study Day
(change from baseline) (change from baseline)
Screening 31.88 32.25
28 27.08 (-4.8) 28.03 (-4.22)
56 25.69 (-6.19) 27.75 (-4.5) Distributed by:
Zoetis Inc.
Field Effectiveness Study #2 Kalamazoo, MI 49007
A 112-day, masked, randomized, controlled field study was conducted at 21 U.S. veterinary clinics.
The study enrolled 275 client-owned cats with clinical signs of osteoarthritis (OA) confirmed by August 2021
radiography and orthopedic examination; enrolled cats weighed 2.5 to 11.4 kg and were 1.6 to
22.4 years old. The enrolled cats were randomized to treatment with SOLENSIA (n=182) or vehicle
control (n=93), administered subcutaneously on Days 0, 28, and 56. Cats were dosed with SOLENSIA
(frunevetmab injection) or vehicle control based on body weight (2.5-7 kg cats received 1 mL,
7.1-14 kg cats received 2 mL).
The primary outcome measure for success for the control of pain associated with OA was comparison
of the owner’s evaluation of CSOM at Day 56 compared to baseline (Day 0, before treatment).
Treatment success was defined as a reduction of at least 2 in the total CSOM score at Day 56
compared with the score at baseline. Cats that had an increase in any individual CSOM activity
score (regardless of the total CSOM score) or that received rescue analgesia prior to Day 56 were
considered treatment failures. Secondary outcome measures included the total CSOM score on
Days 28 and 84; Owner Global Assessments on Days 28, 56, and 84; and total orthopedic pain score
completed by the veterinarian on Days 28, 56, and 84. For the Owner Global Assessment, success
was defined as an owner’s impression of the response to treatment as Good or Excellent (versus
Fair or Poor). Success was not defined for the veterinary-assessed total orthopedic pain score. The
proportion of cats considered treatment successes based on the owner CSOM assessment and the
Owner Global Assessment was greater in the SOLENSIA group compared to the control group for all
68000005A&P - AW v.1
assessments. The mean total orthopedic pain score was lower in the SOLENSIA group compared to
ref.: D300.071 F68
the control group at all post‑dosing assessments.