Date: 2013-02-24
Type of information: Publication of results in a medical journal
phase: 3
Announcement: publication of phase 3 results in the New England Journal of Medicine and presentation at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting in San Antonio, Texas, USA.
(Omalizumab for the Treatment of Chronic Idiopathic or Spontaneous Urticaria. Marcus Maurer et al.February 24, 2013DOI: 10.1056/NEJMoa1215372)
Company: Novartis (Switzerland) Genentech, a member of Roche group (USA - Switzerland)
Product: omalizumab
Action
mechanism: Omalizumab is a biologic therapy unique in targeting immunoglobulin E (IgE). Research is ongoing to understand the mechanism of action of omalizumab in CIU/CSU, and to investigate its impact on the drivers of CIU/CSU. Omalizumab is approved for the treatment of severe allergic asthma under the brand-name Xolair® in more than 90 countries, including the US since 2003 and the EU since 2005. In the EU it is approved for the treatment of severe allergic asthma in children (aged six and above), adolescents, and adults. Following approval in the EU, a liquid formulation of Xolair in pre-filled syringes has been launched in most European countries.
Omalizumab is being jointly developed by Novartis and Genentech. In the US, Xolair® (omalizumab) for subcutaneous use in appropriate allergic asthma patients is co-promoted by Novartis Pharmaceuticals Corporation and Genentech.
Disease: moderate to severe refractory chronic idiopathic/spontaneous urticaria (CIU/CSU)
Therapeutic area: Dermatological diseases - Inflammatory diseases
Country:
Trial
details: The ASTERIA II data are the first Phase III results to be presented from the omalizumab clinical trial program in CIU, which also includes two additional Phase III studies (GLACIAL and ASTERIA I) investigating the efficacy and safety profile of omalizumab over 24-week treatment duration.
ASTERIA II was a global, multi-center, randomized double-blind study that evaluated the efficacy and safety of omalizumab compared to placebo and involved 323 patients aged between 12 and 75 with moderate to severe CIU/CSU. Patients were randomized to omalizumab 75 mg, 150 mg or 300 mg or placebo, given subcutaneously every four weeks, for a total of three doses within a 12-week treatment period, with a 16-week follow-up period2. Omalizumab 150 mg and 300 mg dose groups met the pre-specified primary endpoint and all pre-specified secondary endpoints in the ASTERIA II trial, except for the 150 mg dose that did not show a significant difference from placebo in the proportion of angioedema-free days from Week 4 to Week 12 of therapy. Five (6.3%) patients experienced serious AEs (SAEs) in the omalizumab 300 mg dose group, compared to two (2.5%) in the placebo group. In the 150 mg and 75 mg dose groups, one patient experienced SAEs in each group (1.1% and 1.3%, respectively). No deaths were reported during this study.
Latest
news: * On February 24, 2013, Novartis and Genetech have announced results from a Phase III trial, ASTERIA II, which demonstrated that omalizumab met its primary endpoint in patients with moderate to severe chronic idiopathic urticaria (CIU), who remained symptomatic despite treatment with approved H1 antihistamine doses1. The data were published in the New England Journal of Medicine and have been presented at the American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting in San Antonio (Omalizumab for the Treatment of Chronic Idiopathic or Spontaneous Urticaria. Marcus Maurer et al.February 24, 2013DOI: 10.1056/NEJMoa1215372).
Late-breaking results from ASTERIA II, a Phase III placebo-controlled study, demonstrated that omalizumab provided effective treatment in patients with moderate to severe refractory chronic idiopathic urticaria (CIU), also referred to as chronic spontaneous urticaria (CSU), who remain symptomatic despite treatment with approved antihistamine doses.
The study met its primary endpoint, showing that omalizumab given at doses of 150 and 300 mg every four weeks for 12 weeks, significantly improved the mean weekly ISS (Itch Severity Score) from baseline (approximately 14 in all treatment groups) by 8.1 (p=0.001) and 9.8 (p<0.001), respectively, compared to a 5.1 improvement in patients on placebo. The omalizumab 75 mg dose group did not demonstrate statistical significance compared to placebo.
Patient response, as measured by the median time to Minimally Important Difference (MID), a secondary endpoint, occurred as early as Week 1 (300 mg dose) and Week 2 (150 mg dose), compared to Week 4 in the placebo group. Sixty-six percent of patients in the omalizumab 300 mg group and 43% in the 150 mg group experienced well controlled disease by Week 12, compared to 19% in the placebo group. In the study, disease control was assessed by a weekly urticaria activity score (UAS7), where any score of 6 or less out of a 42 point score is considered to represent well controlled disease. At the end of the treatment period (Week 12), more than three times as many omalizumab 300 mg patients had well controlled disease compared to placebo (66% and 19% respectively).
All eight pre-specified secondary endpoints in the ASTERIA II trial were met for the two dose groups that met the primary endpoint, except for one dose group that did not show a significant difference from placebo in the proportion of angioedema-free days from Week 4 to Week 12 of therapy1. Patient response, as measured by the median time to Minimally Important Difference (MID) in itch severity score, a secondary endpoint, occurred at week one with omalizumab compared with four weeks in the placebo group.
The incidence and severity of adverse events (AEs) was similar across treatment groups. There were no major imbalances in any of the system organ class AEs, with the exception of headache, where more cases were reported in the 150 mg omalizumab group compared with placebo. Nine patients experienced serious adverse events (SAEs): two patients in the placebo group reported SAEs of pneumonia and hemorrhoids; in the three omalizumab dose groups, seven patients reported SAEs of angioedema (two), urticaria, idiopathic urticaria (two), melanoma in situ (onset stage of skin cancer), nephrolithiasis (kidney stones), tonsillectomy, and melena (black blood in stool). No SAEs were suspected to be caused by the study drug or led to withdrawal from treatment1. No deaths were reported during the study.
Omalizumab is jointly developed by Genentech under an agreement with Novartis Pharma AG and is co-marketed in the United States with Novartis Pharmaceuticals Corporation.
Genentech plans to file a supplemental biologics license application (sBLA) with the FDA)for omalizumab in CIU later this year. Novartis regulatory submissions are on track for 2013.
