Cat-PAD Therapeutic Vaccine

Cat-PAD is a new disease-modifying therapeutic vaccine for cat allergy which overcomes the shortcomings of current therapies, has a product profile strongly supported by allergists and patients and is on target to commence a phase 3 clinical trial in 2021.
The Cat-PAD therapeutic vaccine comprises seven synthetic peptides and is administered by intradermal injection.

Cat allergy and current treatments
Cat allergy is common. 17% of the US population (55 million people) and 8% of the EU population skin prick test positive to cat allergen. Cat allergen is strongly associated with asthma. It may also cause rhinitis and conjunctivitis and is associated with significant morbidity and interference with daily activities. This large market is very poorly served.

Antihistamines, glucocorticosteroids and anti-leukotrienes are currently the most common treatments, but these are often only partially effective. They treat the symptoms, not the underlying disease, and require repeated and prolonged treatment courses with common adverse effects.

An alternative approach is the use of whole allergen specific immunotherapy. This is a potentially disease-modifying intervention eliminating allergic symptoms over extended periods and preventing the development of allergic asthma or new allergic sensitizations. Unfortunately the administration of whole allergen to patients sensitized to that allergen risks causing acute systemic adverse reactions, including anaphylaxis, through the cross linking of cell bound IgE.  This necessitates a cautious approach to treatment, resulting in significant drawbacks.  Regimens are inconvenient, onerous, expensive and poorly tolerated.  As a result compliance is poor, with completion rates of only 23% for subcutaneous and 7% for sublingual whole allergen immunotherapy. This means that effectiveness is compromised. These issues necessitated the development of a more sophisticated immunotherapy.

Cat-PAD for treatment of cat allergy
Cat-PAD is a new disease-modifying therapeutic vaccine for cat allergy which overcomes the shortcomings of current therapies.  The Cat-PAD therapeutic vaccine comprises seven synthetic peptide immunoregulatory epitopes (SPIREs) derived from the major cat allergen Fel d 1. Because the peptide chains are short (13 to 17 amino acids) they have a significantly reduced potential to cross-link cell bound IgE, compared with longer peptides or traditional whole allergen immunotherapy. This means there is a has a much reduced risk of causing anaphylaxis and other local and systemic adverse allergic reactions.

Cat-PAD has significant advantages over existing immunotherapies:
•    Less intensive regimen, requiring fewer and less frequent injections (only 4 injections)
•    Significantly shorter course of therapy (3 months vs. 5 years)
•    Sub-cutaneous administration
•    Simpler to use because there is no need for dose escalation, which is required by current immunotherapies
Clinical Data
A phase 2 clinical development programme has demonstrated that administration of Cat-PAD over a 12 to 14 week period was associated with a clinically significant and, in later studies, a statistically significant reduction in allergic symptoms as measured by the Total Rhinoconjunctivitis Symptom Score (TRSS). The treatment effect persisted, with the reduction of symptoms for the selected dose (6 nmol) being more marked and statistically significant one year after the start of treatment compared to that observed at 18 to 22 weeks after the start of treatment. A beneficial effect was maintained for at least two years following the start of treatment in the same subject population although subject numbers were too small to demonstrate statistical significance. The phase 2 trial data were widely regarded as the best that had been achieved in the field, bringing a unique combination of efficacy, safety and convenience. Cat PAD has the potential to enable a paradigm shift in the treatment of allergy.  
The phase 2 efficacy, safety and tolerability findings permitted Circassia Pharmaceuticals to undertake a single pivotal phase 3 clinical field study (CP007). The study was designed and conducted to support registration of Cat-PAD in the United States (US), Canada and the European Union (EU). Although the CP007 study showed excellent safety, unfortunately no statistically significant differences between Cat-PAD treatment groups and placebo were observed and a very large placebo effect was reported.

The failure of clinical registration study CP007 to confirm efficacy of Cat-PAD was a prominent event in the allergy scientific community and in the wake of these results Circassia discontinued the preparation of their planned regulatory submissions.

Subsequent review and evaluation of the CP007 data indicated that the failure to demonstrate efficacy was attributable to inappropriate trial design and in particular the selection of a study population that most likely had developed immunological tolerance to their own cats. Statistical re-analysis of the phase 2 data (CP005/CP005A) according to cat ownership status supports this view. In addition, independently published data showed that allergic subjects who are chronically exposed to cats develop high levels of blocking IgG4 antibodies against the cat allergen , which reinforces this hypothesis.

Adiga Life Sciences has since acquired the assets to Circassia’s allergy technology and intends to run a new phase 3 study with a revised study design.

Commercial Opportunity
Cat allergy is amazingly common - 17% of the US population are skin prick test positive [Arbes 2005]. For Cat PAD, the US market alone could be around 600,000 patients.
The Cat PAD product profile evokes enthusiasm amongst both PCPs and Allergists because it
addresses the unmet medical needs of:
• Less intensive regimen, requiring less frequent injections (only 4 injections)
• Significantly shorter course of therapy (3 months vs. 5 years)
• Cat PAD profile elicits a previously unmentioned need for ease of use and
simplicity - in that there is NO need to adjust the dose (current immunotherapy
requires dose escalation)