Grass MATA MPL Shows 20.3% Symptom Reduction in Phase 3 Allergy Immunotherapy Trial

Stefan Zielen, MD

Credit: Primo Medico

Allergy Therapeutics announced the publication today of promising phase 3 data of Grass MATA MPL, a subcutaneous immunotherapy, for grass pollen allergies.¹

Grass MATA MPL, an aluminum-free, pre-seasonal short-course immunotherapy, was evaluated for treating pollen-related allergic rhinoconjunctivitis symptoms in the G306 phase 3 randomized, placebo-controlled trial, completed in November 2023. Participants (n = 555; mean age: 32.8 years; male: 55.8%) received 6 injections before the allergy season. Patients were either from Europe (n = 488) or the US (n = 67), and most were White (96.4%).²

The G306 trial met its primary endpoint, with participants having a statistically significant reduction in the European Academy of Allergy and Clinical Immunology Combined Symptom & Medication Score (CSMS) of 20.3% (P = .0005) compared with placebo during the peak pollen season. Participants had a significant and clinically meaningful point difference in allergy improvement on Grass MATA MPL compared with placebo (-0.27; 95% confidence interval [CI], -0.42 to -0.12). These findings support the recent submission of the Marketing Authorization Application to the Paul Ehrlich Institute in Germany.

“These comprehensive findings represent an important advance in allergy immunotherapy research,” said lead investigator Stefan Zielen, MD, from Goethe University, Frankfurt.¹ “The data demonstrate that Grass MATA MPL stimulates a broader protective immune response than we typically see, activating multiple antibody pathways that help reduce allergic reactions. This deeper understanding of the treatment candidate's mode of action helps explain the strong efficacy we observed in the Phase III trial and, importantly, the significant improvements patients reported in their daily lives.”

The recent publication included new mechanistic insights into Grass MATA MPL’s mode of action, finding that this immunotherapy works at a molecular level and triggers multiple protective immune responses through the induction of IgG4 and IgA (IgA1 and IgA2) antibodies. This mechanism offers a more comprehensive immunological effect than with other allergy treatments.

Grass MATA MPL includes an extract of 13 grass pollens modified with glutaraldehyde to form allergoids that decrease the reactivity with immunoglobulin E antibodies but do not reduce important immunological properties including T-cell reactivity. The allergoid is absorbed into microcrystalline tyrosine as a depot adjuvant system formulation. Monophosphoryl lipid-A (MPL) is also included to increase immunotherapy's immunogenic effect and boost the switch from allergen-specific helper T-cell Type 2 to helper T-cell type 1.

The comparative analysis showed no other subcutaneous immunotherapy for respiratory allergies has achieved > 14% efficacy improvement in phase 3 trials over the past decade, underscoring the significance of Grass MATA MPL’s 20.3% improvement in allergy symptoms.

Moreover, patients reported significantly better rhinitis quality of life when using Grass MATA MPL, with an improvement of 27.7%, compared with placebo. Rhinitis quality of life was notably greater for patients using Grass MATA MPL than other grass immunotherapy products.

The publication also showed how Grass MATA MPL’s 6-injection format, was more favorable than traditional immunotherapy treatments requiring up to 100 injections or daily tablets over several years. Traditional immunotherapy also had greater discontinuation rates than Grass Mata MPL. In the G306 trial, > 95%of patients completed Grass Mata MPL.

“The publication of our G306 data in Allergy, one of the world's leading allergy journals, provides important validation of our innovative approach to allergy immunotherapy,” said Manuel Llobet, chief executive officer of Allergy Therapeutics. “These results reinforce our confidence in Grass MATA MPL's potential to provide an important new treatment option for patients affected by seasonal grass allergy."

References

1. ^{Allergy Therapeutics - Grass MATA MPL Phase III data published in Allergy. Allergy Therapeutics. Research Tree. February 17, 2025. https://www.research-tree.com/newsfeed/article/allergy-therapeutics-grass-mata-mpl-phase-iii-data-published-in-allergy-2732850. Accessed February 17, 2025.}

2. ^{Zielen S, Bernstein JA, Sturm GJ, Jutel M, Pfaar O; RESONATE Investigator Group; Shamji MH, Mösges R, Berger M, Berger UE, DuBuske L, Layhadi JA, Klimek L, Ollert M, Skinner MA, Kramer MF, de Kam PJ. Six Injections of Modified Adjuvanted PQ Grass Is Effective and Well-Tolerated in a Pivotal Phase III Trial. Allergy. 2025 Feb 4. doi: 10.1111/all.16491. Epub ahead of print. PMID: 39905623.}