Japanese OK In COPD Gives AstraZeneca’s Breztri Aerosphere First Regulatory Approval
Executive Summary
AstraZeneca’s respiratory chief tells Scrip Japan’s approval of the triple-combination inhaled therapy is both a milestone for treating COPD and for the UK pharma’s strategy.
AstraZeneca PLC’s Breztri Aerosphere has been approved in Japan as therapy for chronic obstructive pulmonary disease (COPD), marking the product’s first regulatory approval.
The approval means AZ will join GlaxoSmithKline and Chiesi in marketing a triple-combination therapy for COPD.
Breztri Aerosphere, formerly known as PT010, consists of the long-acting beta-2 agonist (LABA) formoterol, the long-acting muscarinic antagonist (LAMA) glycopyrronium and the inhaled corticosteroid (ICS) budesonide. The product is to be taken twice daily via a pressurized metered-dose inhaler.
The Japanese regulatory approval, announced 19 June, was based on the Phase III KRONOS trial which showed that the triple combo, delivered using the Aerosphere pressurized metered-dose inhaler, demonstrated a significant improvement in eight out of nine lung function primary endpoints in patients with moderate to very severe COPD.
Japan’s Ministry of Health, Labour and Welfare the same day also gave regulatory approval to AstraZeneca’s fixed-dose, long-acting dual bronchodilator Bevespi Aerosphere, combining glycopyrronium and formoterol fumarate as a treatment to relieve symptoms in patients with COPD.
Bevespi Aerosphere is already approved in the US, EU, Canada, Australia and other countries as a dual bronchodilator for the maintenance treatment of moderate to very severe COPD.
“These two approvals in Japan represent an important milestone for AstraZeneca because both of these medicines are on the Aerosphere delivery platform and, in the future, we expect to be able to offer all of the major inhaled combinations on a single device,” said Tom Keith-Roach, who heads up the UK pharma's respiratory, inflammation and autoimmune business.
AstraZeneca's head of respiratory said there is a growing urgency for efficient COPD treatments. “There are 384 million people suffering from COPD globally, and the number is growing,” Keith-Roach said in an interview.
“COPD is the third leading cause of death and typically diagnosed pretty late and characterized by progressive loss of lung function. The median survival of patients following their first severe exacerbation is less than four years, which is worse than many cancers.”
He predicted triple-combination therapy would become increasingly important treatment option for COPD patients and will play a central role in helping them manage their disease going forward.
“The current guidelines for triple-combination therapies recommend that you should wait and only treat patients who have had exacerbations in the last year or two with triple therapy,” he said.
“At this stage, therefore, about one in four patients with COPD are eligible and recommended for a fixed dose triple-combination therapy, because in general today patients will have started on a dual therapy and they therefore will wait until they’ve had two or more exacerbations before they would step up to a triple.”
In the longer term, he said, the company sees the opportunity for triple therapy to be used earlier and significantly more broadly than they are today. “We think two thirds of COPD patients are biologically eligible for triple therapy and that as a class we’ll see an immediate impact in patients with more frequent exacerbations.”
Other Markets
AstraZeneca’s triple combination therapy for COPD is under regulatory review in the US and EU with anticipated regulatory decisions in 2020.
The Chinese National Medical Products Administration has granted a priority review to Breztri Aerosphere, with an expected regulatory decision in the second half of 2019.
GlaxoSmithKline PLC is clearly ahead in the three-in-one COPD market, having received US and EU approval for its product Trelegy Ellipta in 2017 and a Japanese launch in March 2019. (Also see "GSK's Triple Combo COPD Drug Gets Europe Okay" - Scrip, 16 Nov, 2017.)
Trelegy, which was co-developed with Innoviva Inc., comprises the ICS fluticasone, the LAMA umeclidinium and the LABA vilanterol, dosed once daily using GSK's Ellipta dry powder inhaler.
Chiesi Farmaceutici SPA's triple therapy Trimbow (beclomethasone/formoterol/glycopyrrolate), which is approved in Europe in mid-2017, is dosed twice-daily.
Keith-Roach voiced confidence that AstraZeneca’s triple combo Breztri Aerosphere would nonetheless fare well against the competition. “Their product has different molecules and a different anti-inflammatory and is on a different device platform. Breztri Aerosphere has a highly competitive clinical profile beyond those characteristics.“
He added, “What we saw in the KRONOS study which was the basis of this submission and approval was that Breztri provided really rapid and sustained improvements in lung function which is really critical for patients with COPD.”
“Also, in a critical secondary endpoint showed a 52% reduction in the rate of moderate or severe exacerbations versus a versus a LAMA / LABA.”
Keith-Roach said the fact GSK’s Trelegy Ellipta is taken once daily would not put twice-daily Breztri at a competitive disadvantage.
“Market research suggests that some patients prefer once-daily administration while others prefer to get that feeling of rapid lung function improvement twice daily, so it is very hard to generalize.
“It’s the clinical efficacy and clinical profile that will be far more important in driving things like competitive share positioning and patient choice,” he concluded.