Recombinant birch pollen allergoid (folding variant) (Allergopharma)

Pollen extracts and chemically modified allergoids are used successfully in allergen immunotherapy (AIT). Recombinant extracts offer potential advantages with respect to pharmaceutical quality, standardization and dosing. A hypoallergenic recombinant folding variant of the major birch pollen allergen (rBet v 1‐FV) was compared with an established native birch preparation. A pre‐seasonal, randomized, actively controlled phase II study was performed in birch pollen allergic rhino‐conjunctivitis with or without asthma, GINA I/ II. 51 patients (24 rBet v 1‐FV, 27 native extract) started therapy with subcutaneous allergen immunotherapy (SCIT). Primary end‐point was a combined symptom medication score (SMS), changes in nasal provocation test, visual rating score and specific antibody responses secondary end‐points.

After one pre‐seasonal treatment course the combined SMS was 5.86 (median; IQR: 14.02) for the rBet v 1‐FV group versus 12.40 (median; IQR: 9.32) for the comparator during the three weeks pollen season (p = 0.330). After treatment in the second year, scores were 3.00 (median; IQR: 6.50) and 2.93 (4.86) respectively. Allergen tolerance in a nasal provocation test improved to a comparable extent in both groups. Significant increases in birch pollen‐specific IgG1 and IgG4 were observed in both treatment groups following the first treatment phase and remained significantly raised until the end of the study.

In this first in man, proof of concept phase II trial no statistical difference between rBet v 1‐FV and an established natural pollen extract could be observed. rBet v 1‐FV could be administered in higher doses than the native protein with no increase in adverse effects.

The study was registered in ClinicalTrials.gov (NCT00266526).

Recombinant allergens offer a tool for improving specific immunotherapy (SIT).

To find the optimal dose of a new hypoallergenic folding variant of recombinant Bet v 1 (rBet v 1‐FV) as SIT for patients with birch pollen allergy.

Before SIT, thirty‐seven adult patients were exposed for eight hours in an environmental exposure chamber (EEC) to birch pollen at an average concentration of 3500 ± 500 grains/m3, then randomized to four maintenance dose groups of rBet v 1‐FV and one placebo group: 20 μg (n = 7), 80 μg (n = 8), 160 μg (n = 7), 320 μg (n = 8), and placebo (n = 7). Patients were treated for 10 weeks with weekly injections and then re‐exposed in the EEC. The optimal dose for SIT was assessed using efficacy results from the EEC, IgG responses, and tolerability.

Thirty‐six patients were evaluable for efficacy assessment. The total symptom score significantly decreased in all active groups compared with placebo (−18.8% for placebo patients; −71.9%, P = 0.0022 for 20 μg; −75.6%, P = 0.0007 for 80 μg; −81.8%, P = 0.0009 for 160 μg; −78.3%, P = 0.0003 for 320 μg). IgG1 increased significantly in all active groups compared to placebo. All four active doses were well tolerated, no serious adverse event occurred; two Grade II reactions, according to EAACI classification, were observed, one in each of the 160‐ and 320‐μg groups.

Considering efficacy, immunological response, and tolerability, a maintenance dose of 80 μg of rBet v 1‐FV appears to be the ideal dose for allergen immunotherapy in birch pollen allergic patients.