Cat peptide antigen desensitisation for treating cat allergic rhinoconjunctivitis

Figures & data

Figure 1. Schematic illustration of the induction of regulatory T cells by peptide immunotherapy.

Box 1. Drug summary.

Drug name	Cat-PAD
Phase	III
Indication	Disease modifying treatment for rhinitis and conjunctivitis with long-term symptom relief in patients aged ≥ 12 with a history of allergy to cats.
Pharmacology description	Cat-PAD is a mixture of seven MHC II restricted peptides derived from the major cat allergen Fel d 1. Cat-PAD has been designed to avoid cross-linking IgE on mast cells enabling administration of therapeutic doses from the onset of treatment without the need for dose escalation which occurs with conventional immunotherapy. Cat-PAD induces Regulatory T cells which have direct and indirect actions to down-regulate T cell, B cell and Mast cell responses to cat dander allergen.
Route of administration	Intradermal, 4 injections 4 weeks apart
Chemical structure	H-Cys-Pro-Ala-Val-Lys-Arg-Asp-Val-Asp-Leu-Phe-Leu-Thr-OH, hydrochloride H-Glu-Gln-Val-Ala-Gln-Tyr-Lys-Ala-Leu-Pro-Val-Val-Leu-Glu-Asn-Ala-OH, acetate H-Lys-Ala-Leu-Pro-Val-Val-Leu-Glu-Asn-Ala-Arg-Ile-Leu-Lys-Asn-Cys-Val-OH, acetate H-Arg-Ile-Leu-Lys-Asn-Cys-Val-Asp-Ala-Lys-Met-Thr-Glu-Glu-Asp-Lys-Glu-OH, acetate H-Lys-Glu-Asn-Ala-Leu-Ser-Leu-Leu-Asp-Lys-Ile-Tyr-Thr-Ser-Pro-Leu-OH, acetate H-Thr-Ala-Met-Lys-Lys-Ile-Gln-Asp-Cys-Tyr-Val-Glu-Asn-Gly-Leu-Ile-OH, acetate H-Ser-Arg-Val-Leu-Asp-Gly-Leu-Val-Met-Thr-Thr-Ile-Ser-Ser-Ser-Lys-OH, acetate
Pivotal trial(s)	A pivotal phase III study (Catalyst – The Cat Allergy Study) is currently underway.

Pharmaprojects – copyright to Citeline Drug Intelligence (an Informa business). Readers are referred to Pipeline (http://informa-pipeline.citeline.com) and Citeline (http://informa.citeline.com).

Figure 2. Difference in Total Rhinoconjunctivitis Symptom Score (TRSS) at each 30 min time point (3 h per day) in the chamber over 4 consecutive days; score at Baseline Challenge minus score at Post Treatment Challenge (PTC), 8 × 3 nmol Cat PAD and Placebo.

Figure 3. Difference in Total Rhinoconjunctivitis Symptom Score (TRSS) at each 30 min time point (3 h per day) in the chamber over 4 consecutive days 1 year after the start of treatment; score at baseline challenge minus score at post Treatment challenge (PTC), 4 × 6 nmol Cat PAD and placebo.

Table 1. Summary of clinical studies conducted with cat allergen.

Refs.	Product/Dose	Study design	Difference in symptom scores between active and placebo
Larche 2012, Hafner 2012 [29,30]	Cat-PAD 8 × 3 nmol 2 weeks apart or placebo	Environmental Exposure Chamber Challenge consists of 4 consecutive days of three hours at baseline and post treatment challenge. Symptoms scored every 30 min	-2.9
[31]	Cat-PAD 4 × 6 nmol 4 weeks apart or placebo Off dosing for 9 months prior to challenge	Environmental Exposure Chamber Challenge consists of 4 consecutive days of three hours at baseline and post treatment challenge one year after start of treatment. Symptoms scored every 30 min	-3.9
[32]	Cat-PAD 4 × 6 nmol 4 weeks apart or placebo. Off dosing for 21 months prior to challenge	Environmental Exposure Chamber Challenge consists of 4 consecutive days of three hours at baseline and post treatment challenge two years after start of treatment, symptoms scored every 30 min. Symptoms scored every 30 min.	-4.0
[34]	Alutard SQ, ALK, Denmark 2 injections per week with progressive dose escalation until reached maintenance dose after approximately 3 months. Adjustments to the schedule on an individual basis as indicated by large local reactions (> 5 cm diameter) or mild systemic symptoms following previous injection. After reaching maintenance dose (100 000 SQ units containing 15 µg Fel d 1) the next injection was given at 2 weeks and then every 4 weeks thereafter	Cat Room challenge consists of 7 h exposure. Symptoms scored every 5 min for first 15 min, every 15 min for following 2 h and every hour thereafter	-3.0
[39]	Fexofenadine (180 mg) Pre-treatment with fexofenadine or placebo 90 min prior to entry in Cat room	Challenge room with shared ventilation system from a cat shelter. Patients remained in the room until they could no longer tolerate their symptoms: up to 30 min at a baseline visit and 60 min at the treatment visits. Cat bedding (towels) was shaken vigorously before subject entry and once every 15 min while the subjects were in the cat challenge room	-1.3
[35]	Sub-lingual cat allergen drops Drops containing 4.5 µg, 9 µg or 18 µg of Fel d 1/day of ALK cat hair extract or placebo given daily for 16 weeks EEC challenge at baseline at 8 and 16 weeks	Environmental Exposure Chamber Details of challenge duration not disclosed	4.5 µg: 1.2* 9 µg: 0.3* 18 µg: -1.5

*Greater symptoms scores than placebo.

Table 2. Four Phase II prospective, randomized, double-blind, placebo-controlled studies are summarized.

	3 nmol (n =176)	6 nmol (n = 90)	All doses (n = 320)	Placebo (n = 143)
Number of adverse events	270	130	439	193
Number of subjects with adverse events	116 (65.9%)	55 (61.1%)	196 (61.3%)	92 (64.3%)
Number of subjects with serious adverse events	1 (0.6%)	0	1 (0.3%)	1 (0.7%)
Number of subjects with adverse events leading to discontinuation	4 (2.3%)	2 (2.2%)	6 (1.9%)	3 (2.1%)
Relationship to study medication
None	54 (30.7%)	27 (30.0%)	94 (29.4%)	54 (37.8%)
Unlikely/possible	51 (29.0%)	27 (30.0%)	89 (27.8%)	33 (23.1%)
Probable	9 (5.1%)	0	9 (2.8%)	1 (0.7%)
Highly probable	2 (1.1%)	0	2 (0.6%)	4 (2.8%)
Missing	0	1 (1.1%)	2 (0.6%)	0

Subjects were aged 18 – 65 years with documented allergic rhinoconjunctivitis on exposure to cats. Cat-PAD (0.03 – 20 nmol) [or matched placebo] was injected intradermally (n = 284, 131) or subcutaneously (n = 36 [12]). Safety and tolerability were assessed by analyzing adverse events, vital signs, FEV₁, clinical laboratory tests, breathlessness and nasal symptoms, and inspection of the injection site.

Reproduced with permission from poster presented at AAAAI 2013 (Haumann 2013 [40]).

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