Results Presented for 2 Allergic Rhinitis Immunotherapy Treatments Awaiting FDA Action

Two oral immunotherapy treatments for allergic rhinitis being developed by Merck and ALK-Abello, which received separate approvals in recent months from the Allergenic Products Advisory Panel (APAC) of the US Food and Drug Administration (FDA),^1,2 are the subject of results presented Monday at the 2014 Annual Meeting of the American Academy of Allergy, Asthma & Immunology in San Diego, California.

The therapies are MK-7243, to be marketed as Grastek, which would treat patients with pollen-induced allergies to Timothy grass,³ and MK-3641, which would treat ragweed allergies and be marketed as Ragwitek.⁴ Both are tablets that rapidly dissolve under the tongue, a feature that helped Grastek win a recommendation for patients as young as 5 years of age.¹ Ragwitek, however, is only being reviewed for adults ages 18 to 65.²

While ALK-Abello markets Grastek in Europe under the name Grazax,³ such therapies are not available in the US for these types of allergies; patients instead rely on allergy shots for long-term relief from symptoms. The FDA is reviewing another immunotherapy to treat multiple grass allergens—Stallergenes' Oralair—but the advisory panel only gave a recommendation for children ages 10 and older due to insufficient data on children younger than 10.⁵

One abstract was presented Monday on MK-7243, which received advisory panel approval December 12, 2013. It showed that the effectiveness of treatment is highly correlated with the level of pollen exposure; thus, exposure levels should be taken into account when comparing results among different pollen immunotherapy trials.⁶

Researchers reviewed results from 7 trials in North America and Europe to evaluate the relationship between the level of pollen exposure and how well the treatment worked. This early season-efficacy correlation does not confirm prevailing theories regarding “priming,” the phenomenon in which allergy sufferers may be able to tolerate larger amounts of an allergen early in the season, followed by less and less as the season progresses.

Typically, trials for seasonal allergy treatments begin when symptoms appear. But pollen immunotherapy trials generally start before the season, to assess how well treatment works once the pollen season hits. This variability of pollen season exposure could have an effect on the outcome of an immunotherapy trial, which the researchers sought to investigate.

Among the studies included in the review, predefined preseasonal treatment ranged from 8 to 16 weeks. Boundaries of 3 consecutive days with pollen count ≥10 grains/m³ defined the grass pollen season, known in the study as GPS. Researchers then used a measurement known as the total combined score (TCS), which represented a combined symptom/medication score. The study assessed the correlation of between-treatment difference in a TCS, per trial or trial year, to the first-20-days-of-GPS cumulative grass pollen count and the entire-GPS average pollen count.

The results covered a total of 1798 patients receiving the MK-7243 therapy and 1765 receiving a placebo. TCS for both groups increased with grass pollen counts. Treatment effect in TCS in each trial (or trial year) was correlated to cumulative grass pollen count during first 20 days of GPS. Correlation was also seen between TCS and average pollen count over entire GPS.

Two abstracts were presented Monday on MK-3641, which received APAC approval January 28, 2014. The first abstract explained how researchers investigated whether patients who had asthma in addition to ragweed allergies had additional adverse events (AEs) or benefits from the immunotherapy. Asthma is a frequent comorbidity of allergic rhinitis, with or without conjunctivitis.⁷

Patients with ragweed allergies were randomized to either take the study medication once a day or placebo for a year. Those patients with ragweed allergies and asthma receiving the medication saw their TCS reduced 17% at a lower dose, or 6 units of Ambrosia artemisiifolia major allergen 1 (Amb a 1-U) or 22% at a higher dose (12 Amb a 1-U) over the 15-day peak season. Those without asthma saw their TCS reduced 21% at the lower dose and 27% at the higher dose. At least 1 treatment-related AE occurred along the following breakdowns: among asthma patients, 33% on placebo, 63% on low-dose, and 65% on high-dose; among those without asthma, 24% on placebo, 54% on low-dose, and 60% on high-dose. No treatment-related serious or life-threatening AEs or sensitivities were observed.

A second abstract presented on MK-3641 highlighted that the immunotherapy did not lose its effectiveness for patients with multiple sensitivities. Pooled data from 2 randomized controlled trials investigating the drug at the lower and higher doses (6 and 12 Amb a 1-U) were used. Researchers tracked efficacy using TCS during the 15-day peak season.

Results showed the entire study population receiving the ragweed immunotherapy had TCS improvements compared with those on the placebo, 20% for the lower dose and 23% for the higher dose. Those sensitive to ragweed only scored 15% and 19% higher than those on placebo, respectively; those with multiple sensitivities scored 21% and 27% higher.⁸

References

1. Brown T. Grastek recommended by FDA panel for Timothy grass allergy. Medscape Multispecialty. http://www.medscape.com/viewarticle/817771. Published December 12, 2013. Accessed March 2, 2014.

2. Phend C. FDA panel backs oral Tx for ragweed allergy. Medpage Today. http://www.medpagetoday.com/AllergyImmunology/Allergy/44023. Published January 28, 2013. Accessed March 2, 2014.

3. Merck Statement on FDA Advisory Committee for GRASTEK® (Timothy Grass Pollen Allergen Extract), Merck’s Investigational Sublingual Allergy Immunotherapy Tablet [press release]. Whitehouse Station, NJ: December 12, 2013. http://www.mercknewsroom.com/news-release/prescription-medicine-news/merck-statement-fda-advisory-committee-grastek-timothy-grass. Accessed March 2, 2014.

4. Merck Statement on FDA Advisory Committee Meeting for RAGWITEK (Short Ragweed Pollen Allergen Extract), an Investigational Sublingual Allergy Immunotherapy Tablet [press release]. Whitehouse Station, NJ: January 28, 2014. http://www.mercknewsroom.com/news-release/merck/merck-statement-fda-advisory-committee-meeting-ragwitek-short-ragweed-pollen-alle. Accessed March 2, 2014.

5. Taylor P. FDA backs a brace of allergy immunotherapies. PMLive. http://www.pmlive.com/pharma_news/fda_backs_a_brace_of_allergy_immunotherapies_527790. Published December 16, 2013. Accessed March 2, 2014.

6. Nolte H, Durham S, Nelson HS. Magnitude of changes in patient symptom and medication scores in grass allergy immunotherapy trials dependency on levels of pollen exposure. J Allergy Clin Immunol. 2014;133(2):1A-4A (suppl);Abstract 767.

7. Maloney J, Bernstein DI, Hebert J, et al. The efficacy and safety of the short ragweed sublingual immunotherapy tablet MK-3641 is similar in asthmatic and nonasthmatic subjects treated for allergic rhinitis with/without conjunctivitis. J Allergy Clin Immunol. 2014;133(2):1A-4A (suppl);Abstract 754.

8. Bernstein DI, Murphy KR, Nolte H, Amarjot K, Maloney J. Efficacy of short ragweed sublingual immunotherapy (SLIT-T) in mono-sensitized and poly-sensitized subjects. J Allergy Clin Immunol. 2014;133(2):1A-4A (suppl);Abstract 756.