AstraZeneca's Forxiga and Trixeo Aerosphere Recommended by CHMP for Heart Failure and COPD

Compiled by Keke

On October 19, AstraZeneca announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) had recommended the approval of an expanded indication for Forxiga (dapagliflozin) for marketing in the European Union (EU). The indication is for the treatment of adult patients with symptomatic chronic heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes (T2D).

Meanwhile, the company’s Trixeo Aerosphere (formoterol fumarate/glycopyrronium bromide/budesonide) has also been recommended by the CHMP for marketing in the EU for the treatment of adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who have not been adequately treated with a combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA), or with a combination of LABA and long-acting muscarinic antagonists.

Forxiga

Based on the results of the landmark Phase 3 clinical trial DAPA-HF published in The New England Journal of Medicine, the CHMP issued a positive opinion on the indication expansion for Forxiga.

DAPA-HF was an international, multicenter, parallel-group, randomized, double-blind Phase 3 clinical trial that enrolled 4,744 patients with heart failure with reduced ejection fraction (HFrEF; LVEF ≤40%), with or without type 2 diabetes (T2D), to evaluate the efficacy and safety of adding 10 mg Forxiga versus placebo to standard care. The primary composite endpoint was time to first worsening heart failure event (hospitalization or an equivalent event, i.e., urgent heart failure visit) or cardiovascular death. The median follow-up duration was 18.2 months.

The DAPA-HF study demonstrated that, compared with placebo, Forxiga plus standard of care reduced the risk of the composite outcome of cardiovascular (CV) death or heart failure (HF) worsening by 26% (hazard ratio [HR]=0.74 [95% confidence interval {CI} 0.65-0.85]; p<0.0001) (absolute risk reduction [ARR]=4.9% [event rates were 16.3% and 21.2%, respectively]).

Meanwhile, researchers found that during the trial period, one CV death or hHF or HF-related emergency visit could be avoided for every 21 patients treated. In addition, the safety profile of Forxiga was consistent with its established safety data. Therefore, the CHMP recommended Forxiga for the treatment of symptomatic chronic HFrEF in adults.

In May 2020, Farxiga was approved in the United States to reduce the risk of cardiovascular death and hospitalization for heart failure (hHF) in adult patients with heart failure with reduced ejection fraction (HFrEF) (NYHA class II-IV); it also met all primary and secondary endpoints in the phase 3 DAPA-CKD trial evaluating patients with chronic kidney disease (CKD).

Furthermore, Forxiga will also conduct the indication-seeking randomized controlled Phase 3 trial DAPA-MI in patients with acute myocardial infarction (MI) or post-heart attack without type 2 diabetes (T2D).

Trixeo Aerosphere

Trixeo Aerosphere is a triple-combination therapy delivered via a single pressurized metered-dose inhaler, comprising the long-acting beta2-agonist (LABA) formoterol fumarate, the long-acting muscarinic antagonist (LAMA) glycopyrronium bromide, and the inhaled corticosteroid (ICS) budesonide. It has been approved for the treatment of patients with chronic obstructive pulmonary disease (COPD) in Japan, China, and the United States under the brand name Breztri Aerosphere.

This CHMP recommendation is primarily based on the results of the Phase 3 ETHOS clinical trial. ETHOS was a randomized, double-blind, multicenter, parallel-group, 52-week Phase 3 clinical trial designed to evaluate the efficacy and safety of Trixeo Aerosphere in patients with moderate-to-severe COPD who had a history of exacerbations in the previous year. The primary endpoint was the rate of moderate or severe exacerbations.

Research results published in The New England Journal of Medicine showed that, compared with the dual-drug therapies Bevespi Aerosphere (glycopyrronium/formoterol fumarate) and PT009 (budesonide/formoterol fumarate), Trixeo Aerosphere significantly reduced the rate of moderate or severe exacerbations in patients over 52 weeks.

Meanwhile, the CHMP’s recommendation was also supported by positive data from KRONOS, a randomized, double-blind, parallel-group, 24-week, chronic-dosing, multicenter Phase 3 trial. In both trials, the safety and tolerability profile of the drug was consistent with that of dual combination therapy.

Reference Sources:

1.Forxiga recommended for approval in the EU by CHMP for heart failure

2.Trixeo Aerosphere recommended for approval in the EU by CHMP for the maintenance treatment of COPD

Original Title:AstraZeneca’s Forxiga and Trixeo Aerosphere Recommended for Approval by CHMP for Heart Failure and COPD