House dust mite allergen immunotherapy

Unassigned

New Medicines

ActairPerennial allergic rhinitis in adolescents and adults

Information

Actair
New formulation
Stallergenes
Stallergenes

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Phase III Clinical Trials
May 20Filed via the European decentralised procedure. Germany is the reference member state and the UK is a concerned member state [9,10].
Dec 19No further development reported [6,7].
Nov 18Stallergenes Greer is planning filings in countries including the US & EU [5].
Dec 16Study NCT02443805 is due to complete Feb 17 [4].

Category

House dust mite allergy immunotherapy is an immunomodulator designed to develop allergy desensitisation.
Allergic rhinitis affects over 20% of the UK population [1], with about 20% uncontrolled on currently available pharmacotherapy and so eligible for immunotherapy (4,000 per 100,000) [2].
Perennial allergic rhinitis in adolescents and adults
Sublingual

Trial or other data

Nov 18 Stallergenes Greer announces topline results for its PIII trial (NCT02443805) to evaluate the efficacy and safety of STG320 for the treatment of house dust mite (HDM)-induced allergic rhinitis. The study met its primary endpoint. Results indicated a statistically significant reduction of the Total Combined Score (p<0.0001), the sum of the Rhinitis Total Symptom Score and the Rescue Medication Score, in patients treated with STG320 compared to patients on placebo. The study also reached key secondary endpoints, including overall quality of life, and showed that the treatment was generally well tolerated, confirming the favorable safety profile observed in previous studies [5].
Dec 16Study NCT01199133 in children and adolescents was terminated in 2011 as study population was insufficiently symptomatic to enable differentiation between treatment and placebo. The ongoing PIII study NCT02443805 is in adolescents and adults [4].
Jun 15Stallergenes is planning a 12-month, PIII study to evaluate the efficacy and safety of sublingual immunotherapy 300 IR tablet for the treatment of patients with HDM-associated allergic rhinitis (SL75.14; NCT02443805). The placebo-controlled, randomised, double-blind study will recruit 990 patients in the US and France [3].
Mar 14A double-blind, PIIb/III trial of the immunotherapy was completed in patients with moderate to severe, persistent allergic rhinitis due to house dust mites (VO57.07; NCT00674700). A total of 509 adults were randomised to one of two doses of the immunotherapy, or placebo, administered once daily. The carry-over effect was evaluated in a treatment-free, 12-month follow-up period, for which results were reported in June 2010 10. The trial was conducted in France, the Czech Republic, Germany, the Netherlands, Poland, Slovakia and Spain [3].
Feb 14 Stallergenes report that Shionogi has completed a randomised, double-blind, placebo-controlled, 12-month P II/III trial of the immunotherapy in Japanese patients aged 12 to 64 years (JapiCTI-121917). Positive top-line results were reported [3].
Sep 09Stallergenes launch a PIII study in children and adolescents aged five to 17 years (VO64.08; NCT01199133). The study aims to assess the safety and efficacy of the sublingual immunotherapy 300 IR in the treatment of perennial allergic rhinitis (caused by house dust mite allergy). The primary endpoint is change from baseline at 12 months in the Average Adjusted Symptom Score. This trial will enrol 471 patients in Germany, France, Ireland, Denmark, Spain, Hungary, Slovakia, Ukraine and Romania; however, the trial was terminated as patients were insufficiently symptomatic to enable differentiation between treatment and placebo [3].

Evidence based evaluations

Acarizax (EU); Odactra (US)Allergic rhinitis and allergic asthma due to house dust allergy - SubLingual ImmunoTherapy (SLIT)

Information

Acarizax (EU); Odactra (US)
New molecular entity
ALK-Abello
ALK-Abello

Development and Regulatory status

Phase III Clinical Trials
Launched
Launched
May 19Has been available in the US since Jan 18 for treatment of HDM-induced nasal inflammation (allergic rhinitis), with or without eye inflammation (conjunctivitis), in patients from 18 through 65 years of age [19].
Dec 18Not filed in the UK yet due to uncertainty over Brexit [18]
Apr 17EU approval for a licence change to allow treatment of adolescent patients aged 12 to 17 years with house dust mite-induced allergic rhinitis [17].
Mar 17Approved in US for allergic rhinitis [16].
Jan 17There are no current plans to launch in the UK [15].
Dec 16Launched for allergic asthma and allergic rhinitis in Germany, Denmark, Finland, Sweden, Slovakia prior to November 2016. Approved in France in Jan 16 and in Spain and Netherlands in Aug 16 [14].
Apr 16US licence application accepted by FDA [12]
Feb 16Filed in US [11].
Nov 1507. Nov 15: Planned for phased launch across EU. No plans to launch in UK [10].
Sep 15Recent EU approval is in 11 countries - Austria, Czech Republic, Denmark, Finland, France, Germany, Italy, Norway, Poland, Slovakia and Sweden [9].
Aug 15ALK’s house dust mite sublingual allergy immunotherapy has been approved in Europe for use in adults who continue to suffer from allergic rhinitis despite symptom-relieving medication, or when allergic asthma is not well controlled by inhaled corticosteroids [8].
Jul 15PIII in US. Plans for filing in the US not yet available [7].
Nov 14MAA for treatment of allergic rhinitis and allergic asthma was accepted for review by the EMA. The MAA is supported by results from the MITRA and MERIT trials, and was filed via the Decentralised Procedure with Germany as the Reference Member State. First EU launches could potentially take place in 2016 [4]
Apr 14Filing is planned in the EU in 2014 for the treatment of allergic rhinitis and allergic asthma. The application will include the results of the MITRA and MERIT trials [3].
Jun 13The company plans to file in the EU in 2014. It is awaiting data from the MITRA PIII trial before filing [1].

Category

Immunotherapy. Once daily dosing.
Allergic rhinitis affects over 20% of the UK population, with about 20% uncontrolled on currently available pharmacotherapy (4,000 per 100,000). Around 90% of people with allergic rhinitis experience at least one day of ocular symptoms per week. About 1 in 2 adults with asthma have an allergic component to their disease, and 80% of children with asthma show skin hypersensitivity to house dust mite.
Allergic rhinitis and allergic asthma due to house dust allergy - SubLingual ImmunoTherapy (SLIT)
Oral

Further information

Yes
To be confirmed

Trial or other data

Feb 21Estimated primary completion date of PIII MT-11 study (NCT03654976) now June 22 [22].
May 19Results of PIII MT-11 study not expected until at least 2021 [20].
Dec 17PIII trial assessing the efficacy and safety of the HDM sublingual immunotherapy (SLIT)-tablet in children and adolescents aged 5-17 years, with HDM allergic asthma starts (MT-11; EudraCT2016-004363-39). The randomised, double blind, placebo-controlled trial intends to enrol approximately 600 patients in Hungary and plans to expand to Bulgaria, Denmark, France, Germany, Hungary, Poland, Russia, Spain, United Kingdom and United States [19].
Apr 16Results of MITRA trial published in the Journal of the American Medical Association [13].
Jun 15Merck & Co (in partnership with ALK) published positive results from a PII environmental exposure chamber trial evaluating the onset and dose-related efficacy of the house dust mite (HDM) sublingual allergy immunotherapy tablet (SLIT-tablet). The randomised, double-blind trial enrolled 124 pts with HDM-induced allergic rhinitis with or without conjunctivitis and with or without asthma. Over 24 wks, pts were treated daily with either a 12 developmental units (DU) or 6 DU dose of the HDM SLIT-tablet, or placebo. Before the trial began, and again after 8, 16 and 24 wks, pts were exposed to HDM allergen using the Vienna Challenge Chamber – placing them in a room containing a precisely controlled HDM allergen load for six hours to induce an allergic response – and asked to score their allergy symptoms every 15 mins. The primary endpoint was the total nasal symptom score (TNSS) and ocular symptoms and asthma symptoms were also recorded. By wk 24, pts reported that the higher 12 DU dose HDM SLIT-tablet improved nose symptoms by 49%, and eye symptoms by 68% vs. placebo. Nose and eye symptoms also improved with the 6 DU dose HDM tablet, but to a lesser extent. The most commonly reported side effects were mild-to-moderate throat irritation and temporary swelling of the mouth after dosing during the first weeks. The company said that these results, together with those from nearly 2,000 pts in ALK’s MERIT and MITRA trials continue to support the development of this product [5,6].
Jul 13Top-line results from the PIII MITRA trial ((MT-04) reported. The placebo-controlled, double-blind, multi-centre trial randomised 834 patients from 13 European countries into 3 treatment arms. Two groups received two different doses of the active tablet, and the third group received placebo for up to 18 months. All patients received treatment with inhaled corticosteroids (ICS) until the last part of the trial, where the ICS were reduced by 50% for 3 months, and then discontinued for another 3 months. Treatment reduced patients´ risks of moderate to severe asthma exacerbations (p<0.05) [2].
Jun 13Top line results reported from the PIII MERIT trial. The randomised, double-blind, multi-national, multi-centre trial enrolled 992 patients from 12 EU countries into three arms. Two groups received two different doses of active treatment and the third received placebo but had unrestricted access to symptom-relieving medication. Patients received treatment once daily for 1 year. The primary endpoint, a reduction in the combined rhinitis symptom and medication score was met (p<0.01). A second PIII study, MITRA (n=834) is evaluating efficacy in reducing asthma exacerbations in patients with allergic asthma caused by house dust mites. Nearly 50% of all house dust mite allergic rhinitis patients suffer from asthma. ALK expects to report the outcome of this trial before end of Q3 2013 [1].

Evidence based evaluations