Update: This peptide therapy ultimately failed in the third phase of study, read the article here.
THE ANCIENT Egyptians were said to revere the cat, glorifying it in hieroglyphs, depictions of deities and artwork. While today’s domestic kitty may not enjoy the same royal treatment, the feline still wields serious power: just being in the same room as one can trigger itching, coughing, wheezing and even a full-on asthma attack in the millions who have cat allergy.
The American Academy of Allergy, Asthma and Immunology says the condition affects an estimated 50 million Americans, including the 30 percent of those with allergic asthma who list cat dander as a key trigger.
Other than simply avoiding cats, immunotherapy, or allergy shots, is the only current treatment option for this allergy. The idea here is to retrain the immune system to accept the cat’s allergy-inducing protein rather than react to it as a dangerous invader.
To do so, the doctor injects small amounts of cat protein extract into the body over several visits, slowly increasing the dosage and then staying at a target level for three to five years. The hope is to achieve desensitization, or at the very least, greatly reduced symptoms.
The process is far from ideal. Not only does it require close to 100 injections, it is incredibly time-consuming, with untold hours spent at the doctor’s office. Not surprisingly, many patients simply quit going. Immunotherapy also always carries a reasonable risk of reaction, since the very thing a person is allergic to is being injected into the body. Anaphylaxis to immunotherapy, while uncommon, certainly has been reported, which is why patients are meant to wait at least half an hour in the doctor’s office after receiving an injection.
Will a 4-Shot Therapy Work?
This is all that’s available today. However, the big news in the allergy and asthma research community is that a new and quicker treatment for cat allergy looms large on the horizon, holding the promise of an end to the widespread grief.
Reports from a clinical trial in 2015 had the allergy field talking. After just four shots of the new product – named Cat-SPIRE – patients experienced a significant decrease in symptoms when exposed to cat allergens. Not four shots per month or year, but just four shots in total, each taken one month apart. Two years later, the results were largely the same.
“That took us all by surprise,” says Mark Larché, an immunologist and professor of medicine at McMaster University in Hamilton, Canada. “To get a two-year effect after just one course of treatment, particularly when it’s only four injections, that’s very encouraging.”
Larché is the co-founder of Circassia Ltd., a British biotech firm that is spearheading the product’s development along with the Canadian company Adiga Life Sciences, which is jointly owned by Circassia and McMaster University.
The key to Cat-SPIRE is the science behind the shot. Circassia scientists take the allergenic cat protein, called Fel d1, and break it down into basic parts called peptides. The building blocks of proteins are called amino acids, and peptides are strings of two or more amino acids. The Fel d1 protein is normally 162 amino acids long, while Cat-SPIRE contains seven synthetic peptides, each 15 amino acids in length, and each hand-picked to generate the desired response.
“Currently available immunotherapy basically takes the thing you’re allergic to and injects it into you,” says Steve Harris, CEO of Circassia and director of Adiga Life Sciences. Cat-SPIRE, he explains, was created by zeroing in on parts of Fel d1 that promote a regulatory, or non-allergic, immune response. By using fragments of Fel d1 created in a lab as opposed to the entire protein, fewer shots are needed, reactivity is lessened, increases in dosage are not required, and so far, the results have been impressive.
Big Phase 3 Study
Patients have now been recruited for a final (or Phase 3) trial that’s meant to confirm the shot’s effectiveness, and also test whether giving eight injections instead of four makes any difference. About 1,400 cat-allergic individuals between the ages of 12 and 65 have enrolled in the trial, which is taking place in multiple sites across the United States, Canada and Russia.
Yet researchers already know that the shot won’t be equally effective for everyone. Dr. Harold Nelson, the principal investigator of the Phase 3 trial, is quick to point out that patients in the previous trial showed an average symptom reduction of 50 percent. This suggests that Cat-SPIRE probably has a strong effect for many individuals, while others will likely benefit to a lesser degree.
The duration of the treatment’s effectiveness is also a question mark. It’s possible that Cat-SPIRE’s effects will last for several years, as conventional immunotherapy does – or perhaps even longer. Nelson, a professor of medicine at National Jewish Health in Denver, is cautious on this point: “We know what conventional immunotherapy does, but this is such a different approach that we don’t know if the duration of effect will be the same.”
From Allergy to ASPCA
But no matter how long the protection will prove to last, some study participants are already enjoying the benefits, according to one of the clinics involved. Cheryl Bernstein of Bernstein Clinical Research Center in Cincinnati has one patient who even began volunteering at the ASPCA before her treatment had finished. The woman, who had been highly allergic to cats, volunteered to clean cages of some 250 cats while navigating her way through a sea of allergens.
“When she told me she was going to do that I thought she was crazy,” says Bernstein with a laugh. “And she actually feels OK; she feels that she can tolerate it.”
While Nelson oversees the big trial, Larché is working in the laboratory, studying the mechanism behind Cat-SPIRE in order to learn more about how it works and to determine which patients will experience the greatest benefit.
“We’re looking for biomarkers of efficacy – simple tests that could be done on patients’ blood that would tell us whether or not they are getting a clinical response, so we know early whether a patient is going to find this helpful or not,” he says.
Larché is optimistic, pointing out that graphs of participants’ symptom scores at a two-year followup study looked almost identical to the one-year graphs. “It looks stable, like it’s sort of locked in,” he says. Patients in the current Phase 3 study will be followed for up to five years to gauge the drug’s lasting effects.
“Of course it begs the question, have we actually induced a life-long remodeling of the immune system?” he says.
The Phase 3 trial is the final step before seeking regulatory approval. However, even if all goes well, the Cat-SPIRE treatment won’t be available for at least a few more years, as the therapy would be subject to the FDA’s regulatory approval process.
Circassia also has other immunotherapy products in development, including those for grass pollen, ragweed and dust mite, all using the same peptide-based technology. Phase 2 trials for these products have shown similar positive results. “So this work is very encouraging,” says Larché. “It’s exciting to think that four shots protect you for several years, or maybe even for life.”