Laird Harrison

March 06, 2014

SAN DIEGO — An experimental sublingual tablet can build tolerance in people allergic to dust mites, researchers report.

The MK-8237 tablet, under development by Merck, reduced nasal symptoms by half and conjunctivitis by two thirds in a phase 2 clinical trial.

"I'm very excited about this," said lead investigator Hendrik Nolte, MD, respiratory section head at Merck. "I see a huge opportunity, especially for children who don't want the injections," he told Medscape Medical News.

Dr. Nolte presented the findings here at the American Academy of Allergy, Asthma & Immunology 2014.

In the United States, 25% to 28% of the population suffers from house dust mite allergies, and the affliction is common around the world.

The treatment resembles 2 other sublingual tablets under development by Merck: Ragwitek for ragweed pollen and Grastek for Timothy grass pollen. The US Food and Drug Administration committee has recommended the approval of both agents. Grastek is already approved in Europe.

 
I see a huge opportunity, especially for children who don't want the injections.
 

The tablets work by exposing the allergy sufferer to minute doses of the allergen, gradually desensitizing them until they don't react as much when they are exposed to the allergen under natural circumstances.

To test the dust mite tablet, Dr. Nolte and his team recruited adults who had suffered for at least 1 year from allergy to the 2 species of dust mites most responsible for allergies: Dermatophagoides pteronyssinus and Dermatophagoides farinae. Allergies were verified with skin prick tests and serum-specific immunoglobulin E levels.

Some patients had asthma, but none had severe or uncontrolled asthma.

The investigators randomly assigned 42 patients to tablets containing 12 units of dust mite allergen, 41 to tablets with 6 units, and 41 to placebo.

Each patient put 1 tablet under the tongue every day for 24 weeks. The tablets dissolve so quickly it is almost impossible to swallow one, Dr. Nolte explained.

Four weeks before the experiment and every 4 weeks after starting the therapy, the patients sat in a specially constructed chamber — known as the Vienna Challenge Chamber — with air filled with dust mite allergen.

Nasal symptoms — runny noses, blocked noses, sneezing, and itchiness — were each rated on a scale of 0 to 3. The sum of these scores produced a score of 0 to 12, where 0 meant no symptoms and 12 meant severe symptoms for all parameters.

Symptoms declined over the 24 weeks in both treatment groups, but not in the placebo group.

Table: Nasal Symptom Scores by Treatment Group

Week 12 Units 6 Units Placebo
8 5.34 6.16 6.71
16 4.82 5.67 6.90
24 3.83 5.47 7.45

 

At week 24, nasal symptoms in the 12-unit group were 49% lower than in the placebo group, and conjunctivitis symptoms were 68% lower. The difference was statistically significant (< .001).

Nearly all the patients reported some adverse reactions to the treatment, including throat irritation, mouth edema, lip swelling, oral pruritus, dyspepsia, ear pruritus, swollen tongue, oropharyngeal swelling, and pharyngeal edema.

Throat swelling, the most common adverse effect, was reported by 52% of the 12-unit group and 34% of the 6-unit group.

Most of the symptoms disappeared after 2 weeks, said Dr. Nolte. No one experienced an airway obstruction or went into anaphylactic shock.

This study builds on a trial reported last year at the European Academy of Allergy and Clinical Immunology annual meeting, said Dr. Nolte. In that trial, the patients were tested for desensitization in their natural settings. Symptoms improved after patients took the MK-8237 tablets, but the results did not as clearly favor the 12-unit dose.

Using an environmental chamber has settled that question, he said. "We believe the 12-unit dose is best to carry forward into a large trial."

Screening of patients has already begun in a phase 3 trial. Dr. Nolte said he hopes the study will be completed by the first quarter of 2015.

He is not the only one looking forward to more definitive results. "I think this is exciting," session moderator Jeffrey Demain, MD, from the Allergy, Asthma and Immunology Center of Alaska in Anchorage, told Medscape Medical News. "It was a very well-designed study."

In addition to the convenience, sublingual immunotherapy appears to be less risky than subcutaneous immunotherapy, said Dr. Demain. Allergy shots can sometimes cause systemic reactions such as hives, and even anaphylaxis.

However, only 0.3% to 3.0% of patients have adverse reactions to the shots. And the shots have another advantage: once patients are desensitized, they can stay that way indefinitely. In contrast, studies of other sublingual immunotherapies have shown that the benefits appear to wear off within a year. Long-term studies on MK-8237 have not yet been done.

This study was funded by Merck. Dr. Nolte is an employee of the company. Dr. Demain has disclosed no relevant financial relationships.

American Academy of Allergy, Asthma & Immunology (AAAAI) 2014: Abstract L17. Presented March 3, 2014.

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