AstraZeneca said it’s not planning to seek approvals for Fasenra™ (benralizumab) in chronic obstructive pulmonary disease (COPD) following the drug’s second Phase III trial failure in less than a month.

Fasenra missed its primary endpoint in the TERRANOVA Phase III trial (NCT02155660) of a statistically significant reduction of exacerbations, AstraZeneca acknowledged. The company offered no details, saying its full evaluation of data was “ongoing,” and that results will be submitted for presentation at an unspecified “forthcoming medical meeting.”

“The Company does not currently intend to make a regulatory submission,” AstraZeneca stated.

In saying so, the company has reversed its plans from February 2, when it released fourth-quarter and full-year 2017 results. Back then, AstraZeneca said it expected to file a regulatory submission next year seeking authorization to market Fasenra for COPD.

TERRANOVA—completed as of May 7, according to—was one of two pivotal studies designed to assess Fasenra in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). On May 11, AstraZeneca acknowledged that Fasenra failed the Phase III GALATHEA trial in similar fashion.

GALATHEA (NCT02138916) and TERRANOVA were both randomized, double-blinded, 56-week placebo-controlled, multicenter trials intended to assess the safety and efficacy of Fasenra as an add-on to dual or triple inhaled therapy compared to placebo in patients with moderate to very severe COPD with a history of exacerbations across a range of baseline blood eosinophils.

GALATHEA evaluated two doses of Fasenra and enrolled 1656 patients; TERRANOVA, three doses and 2255 patients. The studies were both completed last month.

“These results are disappointing because uncontrolled COPD patients already on dual or triple inhaled therapy need new treatment options,” Sean Bohen, M.D., Ph.D., AstraZeneca EVP, global medicines development and CMO, said in the company statement. We will now analyze the complete datasets from the GALATHEA and TERRANOVA trials to further understand these results.”

Safety and tolerability findings in TERRANOVA were consistent with those observed in previous trials with Fasenra, AstraZeneca added.

$2B Peak-Year Sales Projected

By seeking to expand Fasenra’s respiratory indications, AstraZeneca has hoped to fulfill projections stretching back to 2014 that the drug could generate as much as $2 billion in peak-year sales—and better compete with rivals that include GlaxoSmithKline (GSK), which is also seeking to expand approved uses for its marketed respiratory drug Nucala® (mepolizumab).

On March 5, GSK trumpeted Phase III results showing that severe asthma patients who are uncontrolled despite receiving Novartis’ marketed asthma drug Xolair® (omalizumab) experienced improved asthma control when switched to Nucala. The rate of exacerbations requiring oral steroids fell by 64% compared with the previous 12 months, GSK said.

A day later, however, Novartis highlighted a positive recommendation for Xolair in a global guideline on chronic urticaria published by the Dermatology Section of the European Academy of Allergology and Clinical Immunology, the EU-founded network of excellence, the Global Allergy and Asthma European Network, the European Dermatology Forum, and the World Allergy Organization.

Xolair is an anti-immunoglobulin E (anti-IgE) antibody approved for moderate-to-severe persistent asthma in patients 6 years and older with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids. Xolair is also approved for chronic idiopathic urticaria in patients ages 12 and older who remain symptomatic despite H1 antihistamine treatment.

Nucala is an interleukin-5 antagonist monoclonal antibody (IgG1 kappa) approved as an add-on maintenance treatment for severe asthma in patients aged 12 years and older, with an eosinophilic phenotype, as well as for treating adults with eosinophilic granulomatosis with polyangiitis (EGPA).

Fasenra is AstraZeneca’s first respiratory biologic approved and marketed in the U.S. as an add-on maintenance treatment of patients aged 12 years and older with severe asthma and with an eosinophilic phenotype. The treatment is also indicated for severe eosinophilic asthma in the E.U., Japan, Canada, and Australia.

Fasenra is an interleukin-5 receptor subunit alpha–directed cytolytic monoclonal antibody designed to work by recruiting natural killer cells to induce rapid and near-complete depletion of eosinophils. Fasenra was developed by AstraZeneca with MedImmune, the company’s global biologics research and development arm.

Last year, AstraZeneca agreed to pay Kyowa Hakko Kirin $15 million upfront, undisclosed payments for regulatory and commercial milestones, and low double-digit percent sales royalties—in return for exclusive rights to oversee development, sales, and marketing of Fasenra in severe asthma and COPD in 13 Asian countries and regions—except Japan, where AstraZeneca already held the commercialization rights to the drug after exercising in 2016 an option it was granted a year earlier.

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