Regeneron's Positive Phase 3 Allergy Trials Advance First-in-Class Antibody Blockers
Breakthrough Clinical Results
Regeneron Pharmaceuticals announced positive results from two Phase 3 trials evaluating its first-in-class allergen-blocking antibodies for cat and birch allergies. Both trials met primary and key secondary endpoints, demonstrating significant reductions in allergy symptoms (itch, conjunctival redness) after a single dose. The data will support further Phase 3 development and confirmatory trials. The antibodies, REGN1908 and REGN1909 for cat allergies and REGN5713 and REGN5715 for birch allergies, are fully human monoclonal antibodies targeting dominant allergens. The treatment was well-tolerated with no serious adverse events. Regeneron is planning additional Phase 3 development for both indications.
Key Highlights
- Positive Phase 3 results for cat and birch allergy treatments.
- Significant reduction in allergy symptoms (itch, redness) after a single dose.
- Well-tolerated treatment with no serious adverse events.
- Further Phase 3 development planned.
Incidence and Prevalence
Global Prevalence and Incidence of Cat Allergy
Allergic diseases rank among the commonest chronic diseases in developed countries, affecting between 15% and 30% of the population according to recent studies. Specifically, cat allergy impacts approximately 15% of the population and represents a major risk factor for asthma development.
The major cat allergen, Fel d 1, accounts for a significant portion of allergic reactions, with an average of 55% of IgE binding to Fel d 1 in individuals with cat allergy. Interestingly, for 35% of cat-allergic individuals, an allergen other than Fel d 1 had the highest IgE binding specificity. In 70% of these cases, the non-Fel d 1 allergen bound more than half of their IgE antibody. Research has identified Fel d 4, 7, and 8 as the main contributors to this non-Fel d 1 IgE binding response, with these allergens eliciting inflammatory Th2 cytokines to a similar degree as Fel d 1.
In a Mediterranean pediatric population study, sensitization to animal epithelia was found in 44.6% of children with allergic rhinitis. Fel d 1 specifically was recognized by 27.7% of these pediatric patients. Another study revealed that the prevalence of allergic rhinitis was 15.7% among school children, with dust mites being the primary allergen (60.4%) followed by pollen (59.3%).
The immunological response to cat allergens shows interesting patterns. In allergic subjects without cat ownership, the frequency of cat allergen (Fel d 1 and Fel d 4)-specific TH2 cells correlates with higher IgE levels and is linked to asthma. Paradoxically, subjects with cat allergy and chronic cat exposure maintain a high frequency of specific TH2 cells, which correlates with higher IgG4 levels and low sensitization. This suggests that cat allergen exposure induces an IgG4 response in a TH2 cell-dependent manner, potentially leading to desensitization through IgG4 accumulation.
IgG4 binding to Fel d 1 was detected in both subjects with allergy (30%) and subjects without allergy (19%). IgG4 binding to other cat allergens was less prevalent but was found in both allergic and non-allergic groups.
In diagnostic testing, the basophil activation test (BAT) has demonstrated 100% sensitivity in diagnosing cat allergy under specific conditions. Additionally, in a study of 509 sera with positive cat RAST results, natural and recombinant Fel d 1 showed similar positive test results (94.1% and 96.1% respectively), with IgE reactivity to Fel d 1 accounting for 88% of the total IgE response to cat allergens.
Polysensitization (sensitivity to multiple allergens) was present in 66% of pediatric patients in one study, with frequent co-recognition of allergens from different sources, highlighting the complex nature of allergic responses.
Study Design Parameters
Study Design Parameters and Endpoints in Cat Allergy Trials
Study Designs
Several key trials have investigated cat allergies using different methodologies:
- A longitudinal, open-label, proof-of-concept study evaluated the clinical efficacy of cat food containing anti-Fel d 1 IgY antibodies in cat-allergic patients
- This study followed cats for 4 months with daily evaluations for 2 weeks at baseline and after 1, 2, and 3 months
- The MASK-air app was used to track symptoms, work productivity and medications
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From 49 patients screened, 42 were followed up with 33 (78.5%) providing complete data
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Another study with 45 patients with rhinoconjunctivitis used skin testing with the Greer Dermapik device to determine atopic status
- Additional assessments included history, in vitro determination of specific IgE level, and nasal challenge with standardized cat pelt extract
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Parameters evaluated included symptom score and nasal lavage tryptase and prostaglandin D (PGD2) levels
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A comparative study examined the MAST CLA system against skin prick test (SPT) for diagnosing cat allergies in 43 asthmatic children
Primary Endpoints
- The anti-Fel d 1 antibody study used Visual analogue scale (VAS) for global allergy symptoms as its primary endpoint
- This endpoint showed significant improvement (p < 0.0001)
- All symptoms (VAS nose, eye, and asthma), VAS work and the combined symptom-medication score significantly improved after 1 month
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The percentage of uncontrolled days (VAS>20/100) decreased from 64% at baseline to 35% at 1 month and 14% at 3 months
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The skin prick test study evaluated the optimal wheal size for identifying clinical cat allergy
- The standard 3-mm wheal was found to be highly sensitive but only moderately specific
- Optimal cutoffs based on receiver operating characteristic analysis and 95% positive predictive value were 5.5 mm or greater
- A 6-mm cutoff effectively distinguished between cat allergic and non-allergic individuals
Secondary Measurements
- The sensitivity of MAST CLA for cats was 25% with specificity less than 50%
- The overall efficiency of MAST CLA for detecting cat allergy was 44%
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No significant correlation was found between SPT wheal size and MAST CLA grade for cats
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The anti-Fel d 1 study was registered at clinicaltrials.gov: NCT05656482
- A sensitivity analysis in patients with uncontrolled disease at baseline confirmed the main analysis findings
Drug used in other indications
REGN1908 and REGN1909 Indications Beyond Cat Allergy
Based on a thorough review of available clinical trial data, REGN1908 and REGN1909 are currently being investigated primarily for cat allergy (feline allergic rhinitis). However, there is limited public information about trials exploring these monoclonal antibodies for other indications.
Some research suggests potential applications in treating broader allergic conditions beyond just cat allergy, including:
- Asthma associated with cat allergen sensitivity
- Atopic dermatitis with feline allergen triggers
- Multiple allergen hypersensitivity where cat allergens are a component
Intervention Models in Current Trials
The intervention protocols for REGN1908-REGN1909 trials typically follow these models:
- Combination therapy administration where both antibodies are given together
- Intravenous (IV) infusion as the primary delivery method
- Fixed-dose regimens with predetermined amounts of each antibody
- Sequential dosing in some protocols to evaluate safety and efficacy
- Challenge-based assessment where participants are exposed to cat allergens in controlled settings after receiving the treatment
The dosing regimens generally include:
- Single-dose administration followed by extended monitoring
- Multiple-dose schedules with specific intervals between treatments
- Dose-escalation protocols in early-phase trials to determine optimal therapeutic levels
Most trials incorporate comprehensive safety monitoring with regular assessment of:
- Immunogenicity markers
- Pharmacokinetic parameters
- Biomarker evaluation for treatment response
While these monoclonal antibodies show promising results for cat allergy, research into their efficacy for other allergic conditions remains in early developmental stages. Future trials may expand the therapeutic applications based on the mechanism of action targeting specific allergen proteins.
