Single-dose immunotherapy improves outcomes among patients with cat allergies
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Key takeaways:
- A single dose of Regeneron’s REGN1908/1909 significantly prevented reductions in FEV1 compared with placebo.
- Treatment increased the amount of allergen that patients could tolerate by a factor of three.
- The immunotherapy was generally well tolerated with no serious adverse events or deaths.
A single dose of immunotherapy treatment prevented reductions in FEV1 among patients with cat allergies and mild asthma, according to a study published in The Journal of Allergy and Clinical Immunology.
The combination of monoclonal antibodies in the dose offers a potential new approach for treating cat allergy and asthma exacerbations induced by cat allergens, the researchers wrote in the study.
“Cat allergy is one of the most common allergic respiratory diseases, impacting millions of people,” Frederic J. de Blay, MD, PhD, HDR, leader of the chest diseases department of Strasbourg University Hospital in Strasbourg, France, and Meagan P. O’Brien, MD, senior director of early clinical development and clinical sciences at Regeneron Pharmaceuticals, told Healio in a statement.
More than 50% of these patients have co-existing asthma, which is exacerbated by cat allergens, and have limited therapeutic options, de Blay and O’Brien continued.
“We recognized an unmet need for additional options beyond standard of care treatments, including allergen-specific immunotherapy (allergy shots) for these patients, and initiated a phase 2 randomized, double-blind proof-of-concept trial,” they said.
Up to 95% of people with a cat allergy have specific IgE to Felis domesticus allergen 1 (Fel d 1), the researchers reported. The monoclonal antibodies REGN1908 and REGN1909 (Regeneron) are designed to prevent Fel d 1 from binding to IgE and ameliorate IgE-mediated allergic responses.
The study’s design and results
“It’s worth noting that our approach to studying cat allergies was novel in a couple of ways. First, we evaluated the use of a single dose monoclonal antibody cocktail designed specifically for the Fel d 1 cat allergen,” de Blay and O’Brien said.
“Second, the innovative trial design involved a first-of-its-kind allergy challenge model setting that allowed for a constant nebulized cat allergen exposure at a carefully monitored health care center,” they said.
The study involved 56 patients (37.5% men) with cat allergies and mild asthma, aged 18 to 65 years (mean age, 29.2 years; standard deviation [SD], 8). After skin prick testing with serial cat hair allergen titration, participants took part in in pretreatment baseline placebo and cat-allergen challenges in an environmental exposure unit (EEU) at the ALYATEC Environmental Exposure Chamber in Strasbourg.
Participants were exposed to approximately 40 ng/m3 of Fel d 1 in the EEU, which is equivalent to exposure in homes where cats live. Within 2 hours, each participant developed an early asthmatic response (EAR), defined as a 20% or greater loss in FEV1. The median time to EAR was 51 minutes.
Next, 29 participants received a single 600 mg subcutaneous dose of REGN1908/1909, and 27 received a placebo. The researchers performed extended screenings on participants where EEU time increased from 2 to 4 hours on days 8, 29, 57 and 85 after the dose. SPT with serial cat hair allergen titration was performed on days 29, 85 and 113 as well.
The group receiving the immunotherapy did not experience any significant reductions in mean FEV1 on days 8, 29 or 57, but they did experience a 13% mean FEV1 reduction on day 85, which the researchers said was still a significant improvement over placebo.
Also, the median time to EAR for the immunotherapy group on day 8 was greater than 4 hours, exceeding maximum exposure, whereas the median time to EAR for the placebo group was 51 minutes (HR = 0.36; 95% CI, 0.17-0.77). The immunotherapy group maintained these results through day 85.
Additionally, approximately 80% of the placebo group experienced an EAR within 2 hours at all timepoints, whereas approximately 50% of the immunotherapy group did not experience an EAR at any timepoint.
The participants in the immunotherapy group further experienced a threefold increase in the quantity of cat allergen that they could tolerate between baseline and day 8 with a total of 59.6 ng, whereas the placebo group could tolerate 19.6 ng (P = .003).
On day 29, the immunotherapy group tolerated 68.2 ng and the placebo group tolerated 14.1 ng (P < .001). Additional totals included 55.4 ng for the immunotherapy group and 21.9 ng for the placebo group on day 57 (P = .023) and 54 ng for immunotherapy and 12.9 ng for placebo on day 85 (P = .003).
The immunotherapy group vs. the placebo group experienced lower chest tightness scores, with higher scores indicating worse symptoms, at baseline (0.77 vs. 1.06), on day 20 (0.29 vs. 0.74) and on day 85 (0.39 vs. 0.79).
Similarly, the immunotherapy group vs. the placebo group also experienced lower breathing difficulty scores, with higher scores indicating worse symptoms, at baseline (0.77 vs. 0.96), on day 8 (0.37 vs. 0.78), on day 29 (0.27 vs. 0.76) and on day 57 (0.4 vs. 0.82).
SPT produced average area under the curve (AUC) of mean wheal diameters of 3.5 mm for the immunotherapy group and 3.36 mm for the placebo group at baseline. The immunotherapy group experienced decreases with average AUC of mean wheal diameters of 1.25, 2.05 and 2.03 mm on days 29, 85 and 113, respectively, whereas there were no reductions in the placebo group.
Additionally, 22 (75.9%) members of the immunotherapy group reported 76 treatment-emergent adverse events, and 21 (77.8%) members of the placebo group reported 66 treatment-emergent adverse events . There were no serious or severe treatment-emergent adverse events, none led to death and rates of events related to asthma were similar between the groups.
Conclusions and next steps
“We were encouraged by the results of the trial, which showed that a single dose of REGN1908/1909 prevented early asthma reactions in cat-allergic patients with mild asthma as early as 1 week after treatment (the earliest timepoint tested) and for up to 3 months (the longest timepoint tested),” de Blay and O’Brien said.
Options for treating cat allergy include allergen avoidance in addition to preventive pharmacotherapies, but patients often experience persistent moderate to severe symptoms with these treatments, the researchers said.
Subcutaneous and sublingual immunotherapies also represent possible treatments, but the researchers cautioned that they may carry a risk for systemic allergic reactions too.
“The current standard of care is allergen-specific immunotherapy (or allergy shots), which can take months to see clinical benefit and is contraindicated for patients with severe or uncontrolled asthma,” de Blay and O’Brien said.
Based on these findings, the researchers concluded, passive immunotherapy with REGN1908/1909 potentially offers a more convenient approach for patients with cat allergy and asthma exacerbated by cat allergens.
“A randomized, placebo-controlled phase 3 trial is currently enrolling for cat-allergic adolescents and adults with allergic rhinitis who live with a cat. The trial will evaluate the efficacy and safety of REGN1908/1909 and its ability to reduce allergic rhinitis symptoms and use of allergy rescue medication,” de Blay and O’Brien said. “We look forward to sharing those results and next steps for the program in the future.”
For more information:
Frederic J. de Blay, MD, PhD, HDR, can be reached at frederic.deblay@chru-strasbourg.fr. Meagan P. O’Brien, MD, can be reached at meagan.obrien@regeneron.com.
Perspective
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These results are significant. It is surprising that the effects of a single dose lasted up to 85 days, which is better than current medications that are available for preventing asthma attacks. Future research should aim to show reproducibility in a larger trial and also determine how long the effects of that single dose last.
Perspective
Back to TopThese findings are significant and should have been expected, but nobody did, so they are surprising too. The use of antibodies works well in allergies. Here, they are being used against cat allergies. The researchers picked a good set of anti-cat antibodies.
In this study, specific immunotherapy increased tolerance to cat allergen 10-fold in 2 years. Common therapy can be successful too, but this study accomplished a good effect with a much simpler procedure, which was one injection for months of results.
These experiments were performed in a laboratory at very high doses of cat allergen — a thousand times of what my colleagues and I have found — in a form designed to reach deeper into the lungs and produce more effects.
In real life, the eliciting dose is lower, and particles are bigger. The effect of this treatment needs to be shown in real life, but these results are very promising, theoretically sound and much simpler than current therapy.
Of course, patients also could get an air purifier or a cat that emits less allergen, as not all cats release the same amounts of allergen. Nevertheless, this therapy is sound and a nice, simpler approach.
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