Novel drugs for allergy treatment

Various chronic allergic diseases still need treatment options. Novel agents are under investigation or were approved, diversifying options and increasing efficacy.

An expanding family of therapies

Research of possible treatments for chronic allergic diseases is leading to many new current and future options for therapy1. Prof. Peter Schmid-Grendelmeier (University Hospital Zurich, Switzerland) gave an overview of the present situation with regard to various diseases that included asthma, atopic dermatitis (AD), eosinophilic oesophagitis (EOE), food allergy, and chronic rhinosinusitis with nasal polys (CRSwNP). “It all comes together with the so-called type 2 inflammation which is mainly promoted by several key cytokines, like IL-4, IL-13, and IL-5,” Prof. Schmid-Grendelmeier informed, adding that other aspects besides the allergens play a role in the induction of disease.

As for biologics in AD, the IL-4/IL 13 inhibitor dupilumab is already licensed for several years. Sole IL-13 inhibition is the mode of action of lebrikizumab and tralokinumab, the latter being EMA-approved since 20212. “We have other molecules like IL-31, already addressed by nemolizumab to reduce itch, or like thymic stromal lymphopoietin, which is already targeted in asthma; so, there are still novel drugs coming in,” Prof. Schmid-Grendelmeier outlined1. Of course, oral JAK inhibitors are another class of drugs for AD and other allergic diseases that are on the rise.

Options include both JAK inhibitors and biologics

The approved therapeutic options for AD in Switzerland in October 2023 include 3 JAK inhibitors (baricitinib, upadacitinib, abrocitinib) and 3 biologics (dupilumab, tralokinumab, and the only EMA-licensed nemolizumab). These new agents have also been included in the stepped-care plan of new guidelines3. Another compound currently investigated is an anti-OX40 antibody which influences T-cell mediated immunity. “Maybe we can even address disease-modifying aspects with these new drugs, or we can address comorbidities,” Prof. Schmid-Grendelmeier gave a positive outlook on future AD therapies.

Biologics for the treatment of asthma include omalizumab, mepolizumab, benralizumab, and dupilumab; all with different modes of action: anti-IgE, anti-IL-5, anti-IL-5 receptor, and anti-IL-4/13, respectively. “The costs are high, so these drugs are reserved for very severe forms, but they can really be a gamechanger for those patients,” Prof. Schmid-Grendelmeier stated.

CRSwNP must not be underestimated in its burden on the affected patients, who additionally often suffer from e.g. comorbid asthma and allergic rhinitis1,4. A review evaluated that the new options of omalizumab, mepolizumab, and dupilumab, but also the classic treatment of aspirin desensitisation, all improved quality of life and reduced the likelihood of surgery versus placebo to a different extent, with dupilumab demonstrating the most favourable results1,5. In phase 3, 46% of patients reached a clinically important response with a ≥2-point improvement of the nasal polyp score6. Osteoprotegerin has been identified as a possible predictor of treatment outcome with dupilumab in patients with nasal polyps7.

Diversification of subcutaneous, sublingual, oral, and epicutaneous formats

“Another disease which we investigated is drug-related eosinophilia with systemic symptoms (DRESS),” Prof. Schmid-Grendelmeier informed, specifying that this drug-induced syndrome can be life-threatening due to extremely high measures of eosinophils. Among the causative drug classes, the most common are anti-convulsants and sulphonamides8. In addition to the classically used systemic corticosteroids, cyclosporin and anti-IL-5 agents show promise1,8,9.

Prof. Schmid-Grendelmeier underlined that specific immunotherapy plays a very important role in the treatment of immediate-type inhalation allergies and insect allergies. “Besides subcutaneous immunotherapy and sublingual immunotherapy which are both established, we have oral immunotherapy, epicutaneous approaches for example for peanuts in children, and we have the approach via the lymph nodes,” Prof. Schmid-Grendelmeier listed.

For the lymph node application of immunotherapy, a trial is presently performed at the Zurich University Hospital. He outlined that the initial findings seem promising with only 3 injections, 10% of the allergen needed, and few local reactions. Another novel approach is the use of engineered virus-like peanut particles as vaccination against peanut allergy, that has been tested in phase 2 with encouraging results10.

References
  1. Schmid-Grendelmeier P. New drugs for chronic allergic diseases. D2T05.1C, EADV Congress 2023, 11-14 October, Berlin, Germany.
  2. Bieber T. Nat Rev Drug Discov. 2022;21:21-40. 
  3. Wollenberg A, et al. EuroGuiDerm Guideline on Atopic Eczema. Version 2.1, December 2022.
  4. Schleimer RP. Annu Rev Pathol. 2017:12:331-357.
  5. Oykhman P, et al. J Allergy Clin Immunol. 2022;149:1286-95.
  6. Bachert C, et al. Lancet. 2019;394:1638-50.
  7. Soyka AM, et al. Allergy. 2023;78:1036-1046.
  8. Kridin K, et al. J Eur Acad Dermatol Venereol. 2023;37:753-762.
  9. Schmid-Grendelmeier P, et al. J Allergy Clin Immunol Pract. 2021;9:481-83.
  10. Storni F, et al. J Allergy Clin Immunol. 2020;145:1240-53.