Novartis takes Xolair follow-up into phase III hives trial

Novartis says it intends to move a drug for chronic spontaneous urticaria (CSU), a severe form of hives, into a phase III programme on the strength of a mid-stage study.

The new drug – called ligelizumab (QGE031) – is being positioned as an improved follow-up to the Swiss company’s blockbuster Xolair (omalizumab), which has lost patent protection in the US and Europe and has biosimilar competition coming through the pipeline.

Like Xolair, ligelizumab works by blocking the activity of immunoglobulin E, the main antibody culprit involved in allergic reactions such as hives, by preventing them from binding to mast cells and basophils and causing them to release histamine.

The new antibody is more effective at reducing IgE levels than Xolair, however, and Novartis hopes that will translate to improved efficacy against the intensive itching and skin weals that characterise the disease and can last for weeks at a time.

Xolair is approved as an add-on therapy for the treatment of CSU, and is currently the only therapy recommended for use in CSU patients who do not respond to standard antihistamine therapy. It’s also approved for severe allergic asthma.

In the phase II trial, ligelizumab showed a clear dose-response effect on CSU symptoms such as swelling in the skin and itchiness, and outperformed Xolair on a number of measures.

Overall, twice as many patients on ligelizumab had a complete response as defined by the Urticaria Activity Score over seven days (UAS7), with more than 50% of patients on the highest dose level (240 mg once monthly) hitting that endpoint. It also seemed to act more quickly, showing an improved response rate over its parent drug as early as four weeks after starting treatment, and patients took longer to relapse after treatment was stopped.

The data has prompted Novartis to start a pair of phase III trials of ligelizumab – PEARL 1 and PEARL 2 – to further explore its safety and efficacy compared to Xolair in more than 2,000 adolescent and adult subjects with CSU who remain symptomatic despite antihistamine treatment. The primary outcome will measure absolute change from baseline in UAS7 at Week 12.

“CSU has a big impact on patients' lives,” according to Marcus Maurer, an allergy specialist at the Charité-Universitätsmedizin in Berlin, Germany, who presented the phase II data a few weeks ago at the EADV Congress in Paris.

“Despite existing treatment options, too many people continue to struggle with the debilitating and potentially painful symptoms of CSU. Advancing ligelizumab to phase III is encouraging news for physicians and patients who have difficulty in controlling symptoms.”

Novartis reported $771m in sales for Xolair in the first nine months of 2018 and is on course to top $1bn for the full-year – although that could decline quickly if biosimilars reach the market. It also shares co-promotion rights to the drug in the US with Roche’s Genentech unit, which booked $1.7bn in sales of the product last year.

If approved, ligelizumab could help Novartis maintain its anti-IgE franchise after Xolair biosimilars from the likes of Glenmark, Fountain Biopharma and Sorrento/Mabtech reach the market.

It could also switch Novartis and Roche from partners to opponents in the market however, as Roche is developing its own CSU candidate fenebrutinib, an orally-administered BTK inhibitor that has reached the phase II trial stage.