The Tale of Oral Immunotherapy for Allergy Rhinitis: Europe Has Approvals, US Has the Ragweed

A sunrise session on climate change, followed by Tuesday’s poster session on allergen immunotherapy at the 2014 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) in San Diego, California, highlighted the irony: Thanks in no small part to the cost of navigating the approval process of the US Food and Drug Administration (FDA), Europe has more options to treat seasonal allergies, even though America has far more ragweed.

Oral immunotherapy to treat allergic rhinitis has been available in Europe for years. At the moment, there are no approved oral immunotherapy solutions for American seasonal allergy sufferers, although a few have cleared the FDA’s Allergenic Products Advisory Panel (APAC).^1,2

The roster of presenters Tuesday underscored the differences. There was Merck, which has partnered with ALK-Abello on 2 FDA approvals for immunotherapy tablets, including 1 for a grass allergy therapy already sold in Europe.^1,2 There was Stallergenes’ 300IR, also sold in Europe, and also awaiting the FDA’s green light to be marketed to grass allergy sufferers.^3,4

And then there was Sevapharma, a Czech company that has been around since the 1920s.⁵ A study on the company’s metered drops,⁶ which are applied under the tongue every other day, reported that the drops worked equally as well on patients with a single sensitivity and on those with multiple allergies.

Would Sevapharma seek a US partner and try to market its drops here? There are no plans at this time, said Lawrence M. DuBuske, MD, a coauthor on the study and clinical professor of Medicine at George Washington University Medical Faculty Associates in Washington, DC.

Over several days at AAAAI, Dr DuBuske and others discussed the challenge and costs of getting through the FDA regulatory process. It’s so daunting that many companies whose products are successful in Europe don’t even try.

Yet immunotherapy holds great promise. In her plenary session on Saturday, March 1, AAAAI President Linda Cox, MD, took the discussion of immunotherapy beyond how it works to treat allergies to how biomarkers might help predict responses to specific pollens.

Results were also presented on Tuesday for 2 immunotherapy tablets still awaiting final word from the FDA: the Merck/ALK-Abello ragweed treatment MK-3641, to be marketed as Ragwitek; and Stallergenes’ 300IR, to be marketed as Oralair.^3,7

Oralair and ALK-Abello’s immunotherapy product for Timothy grass allergies, Grastek, both received APAC approval in December. (Grastek is marketed under a different name in Europe.)⁸ Ragwitek cleared APAC on January 28, 2014.

In the Sevapharma study, led by Ludmila Maslova, MD, of Belarus, 60 patients with pollen, dust mite, and mold allergies who were treated for 2 years with Sevapharma’s specific immunotherapy with allergen extracts.⁶ Half the patients were treated with individual tree, grass, or weed pollen extracts; the other half were patients with multiple sensitivities. Of this group, 15 were treated with pollens and dust mite extracts and 15 were treated with pollen and mold extracts. In all cases, treatment included build-up and maintenance phases.

Researchers found the treatment effective, both in controlling patients’ symptoms of allergic rhinitis and their need for other drugs; they reported a “highly significant” 60% drop in symptom/medication scores, even among the patients with multiple allergies. Adverse effects were reportedly limited, mild, local reactions.⁶

The need for better seasonal allergy treatments, particularly for ragweed, came up early Tuesday at a panel that discussed how climate change is affecting the life of the allergist. John Cohn, MD, professor of medicine and pediatrics at Thomas Jefferson University, Philadelphia, PA, reviewed multiple studies and maps of the US Department of Agriculture hardiness zones, which show that the varieties of what plants can survive is gradually shifting northward. Ragweed appears to have special abilities to thrive amid higher levels of carbon dioxide, especially in cities; ragweed remains comparatively uncommon in Europe.

The move to allow Americans to move from immunotherapy shots to tablets would mark a significant change, as these patients could take the tablets at home. Yet there was no mention of this at Monday afternoon’s annual FDA update session. Badrul A. Chowdhury, MD, PhD, director of Pulmonary, Allergy, and Rheumatology Products at the FDA, gave an overview that listed recent approvals with no discussion of the pipeline, and instead spent time mentioning the withdrawal of inhalers with chloroflurocarbons, a process that is already over.

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. Didier A, Wahn U, Amistani Y, and Zeldin RK. Efficacy of 300IR 5-grass pollen sublingual tablets in grass pollen-associated allergic rhinoconjunctivitis: pooled analysis by level of pollen exposure. . J Allergy Clin Immunol 2014;133(2):1A-4A (suppl);Abstract 968.

4. 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.

5. Sevapharma website. http://www.sevapharma.cz/history_en.php. Accessed March 4, 2014.

6. Maslova L, Titov LP, DuBuske LM. Allergen specific immunotherapy in monosensitized and polysensitized allergic rhinitis patients. J Allergy Clin Immunol 2014;133(2):1A-4A (suppl);Abstract 971.

7. Gawchik SM, Creticos PS, Murphy KR, et al. The effect of the ragweed sublingual immunotherapy tablet MK-3641 on rescue medication use. . J Allergy Clin Immunol 2014;133(2):1A-4A (suppl);Abstract 972.

8. 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.