Omalizumab (Xolair) PBS listed for use in children with asthma

Omalizumab is a recombinant, DNA-derived, monoclonal anti-immunoglobulin E antibody that binds circulating immunoglobulin E (IgE), thereby preventing it from binding to mast cells and basophils, leading to reduced allergic responses.²

Omalizumab was first recommended for PBS listing in November 2010 as a Section 100 (Highly Specialised Drugs Program), written Authority-required item for treatment of adolescents and adults with uncontrolled, severe allergic asthma who:¹

• failed to achieve adequate control despite optimised asthma therapy
• had a total serum IgE concentration ≥ 76 IU/mL
• fulfilled certain other criteria.^b

The PBS listing has been extended to include patients with IgE concentration ≥ 30–75 IU/mL.

b.     The clinical criteria for the use of omalizumab are extensive. The full list is available on the
        PBS website.

• The PBAC was satisfied that omalizumab provides, for some children and adults, a significant improvement in efficacy over placebo plus optimised asthma therapy. The recommendation for extension to children was made because clinical trial evidence demonstrated similar outcomes in children compared with those in adults.¹
• Limited options are currently available to treat this childhood age group, and long-term oral steroid use is unfavourable.¹
• The PBAC noted the clinically significant exacerbation rate was significantly lower in omalizumab plus optimised asthma therapy compared with placebo plus optimised asthma therapy in each of the analysis groups (moderate to severe, and severe paediatric allergic asthma).¹
• Limited paediatric safety data were considered in combination with additional data from the US and Canada.¹
• The PBAC considered the economic model to be reasonable (a cost-effectiveness analysis presented in the form of cost per clinically significant exacerbation avoided, and supported by accepted evidence for cost-effectiveness in adolescent and adult populations).¹

The listing is based on the adolescent/adult PBS restriction of omalizumab, with one minor change for use in children. The key change is that a criterion for adequate response to omalizumab has been added to the paediatric restriction: ‘a reduction in time-adjusted exacerbation rate compared with 12 months before baseline’.¹

The submission to the PBAC was based on one head-to-head, randomised controlled trial (Study IA05) comparing omalizumab plus optimised asthma therapy to placebo plus optimised asthma therapy (n = 628) and six supplementary studies.¹

A 2014 Cochrane review of the evidence for both adults and children found:³

• a consistent reduction in asthma exacerbation rate irrespective of baseline lung function in the omalizumab-treated group
• omalizumab-treated patients required fewer days of asthma rescue medication
• omalizumab use decreased ICS in users
• fewer hospitalisations in those treated with omalizumab.

On the basis of direct-comparison evidence presented by the submission, for every 100 patients treated with omalizumab plus optimised asthma therapy in comparison with placebo plus optimised asthma therapy, there was a reduction of approximately 71 clinically significant exacerbations over a duration of 52 weeks.¹

The supplementary before/after studies all showed a reduction in clinically significant exacerbations from before to after treatment. The reduction in clinically significant exacerbations due to omalizumab treatment was larger in the supplementary studies compared with Study IA05.¹

Adverse events

The most commonly experienced adverse events with omalizumab therapy included nasopharyngitis (27.8% of patients), upper respiratory tract infections (URTIs) (16.4% of patients) and headaches (13.8% of patients).¹

In clinical trials with patients 6 to < 12 years of age, the most commonly reported adverse reactions were headache, pyrexia and upper abdominal pain. Most of the events were mild or moderate in severity.²

Omalizumab has a complex restriction. Patients must, in the first instance, be in the care of a respiratory physician, clinical immunologist or allergist; or a paediatrician or general physician experienced in the management of patients with severe asthma in consultation with a respiratory physician, and meet a range of eligibility and response criteria.^4,5

Omalizumab is an add-on treatment (last line therapy) for managing severe allergic asthma in patients who are treated with maximal recommended asthma maintenance medication yet remain symptomatic.

Omalizumab is effective and well tolerated in children aged 6 and over with moderate to severe allergic asthma,^6,7 but safety data are currently insufficient  to support the use of omalizumab in children under this age.⁸

The prescribing of omalizumab in children with asthma should be done in conjunction with a paediatrician, respiratory physician or immunologist.⁸

Prescribing physicians should ensure that children (6 to < 12 years of age) with IgE < 200 IU/mL have unequivocal in vitro reactivity (RAST) to a perennial allergen before starting therapy.⁸

Dosage for allergic asthma

Omalizumab is administered as 75–375 mg subcutaneously every 2 or 4 weeks.²

Doses (mg) and dosing frequency are determined by baseline serum total IgE concentration (IU/mL), measured before the start of treatment, and bodyweight (kg).²

Doses > 750 mg were not studied in the pivotal clinical studies and are not recommended.

Treatment duration, monitoring and dose adjustments⁹

• Doses do not need to be adjusted for variations in serum IgE over time.
• Dose assignment after treatment interruptions or discontinuations should be based on serum IgE concentrations obtained at initial dose assignment. Serum IgE should only be redetermined for dose assignment if treatment has been discontinued for 1 year or more.
• Doses will need to be increased for bodyweight gains.
• Patients need to be assessed for treatment effectiveness (marked improvement in overall asthma control) 16 weeks after starting Xolair therapy.
• Gradual reduction of inhaled corticosteroids (under supervision) may be attempted after 16 weeks of treatment with Xolair in patients with stable well-controlled asthma. In some patients, inhaled corticosteroids can be tapered off completely.