AstraZeneca gets three new drug approvals in Japan

AstraZeneca announced three new drug approvals in Japan on Wednesday, with the first for ‘Breztri Aerosphere’ (budesonide/glycopyrronium/ formoterol fumarate) - formerly PT010 - as a triple-combination therapy to relieve symptoms of chronic obstructive pulmonary disease (COPD).

The FTSE 100 pharmaceuticals giant said it was the first global regulatory approval for Breztri Aerosphere, and was the first approval by the Japanese Ministry of Health, Labour and Welfare for a triple-combination therapy in a pressurised metered-dose inhaler (pMDI), which used the ‘Aerosphere’ delivery technology.

It said the approval was based on positive results from the phase 3 ‘KRONOS’ trial, in which Breztri Aerosphere demonstrated a statistically-significant improvement in trough-forced expiratory volume in one second - the primary endpoint for Japan - compared with the dual comparators ‘Bevespi Aerosphere’ (glycopyrronium/formoterol fumarate) and ‘PT009’ (budesonide/formoterol fumarate).

“Chronic obstructive pulmonary disease affects more than five million people in Japan, and Breztri Aerosphere offers these patients a new, powerful triple-combination therapy in a pressurised metered-dose inhaler,” said AstraZeneca’s executive vice-president of biopharmaceuticals research and development Mene Pangalos.

“This first approval of Breztri Aerosphere is a significant step towards providing a new treatment choice for people living with chronic obstructive pulmonary disease globally.”

AstraZeneca also said the Chinese National Medical Products Administration had granted a priority review to Breztri Aerosphere, with an expected regulatory decision in the second half of 2019.

The medicine was also under regulatory review in the US and the EU, with anticipated regulatory decisions in 2020.

AstraZeneca today said the second approval in Japan was for Bevespi Aerosphere as a fixed-dose, long-acting dual bronchodilator to relieve symptoms in patients with COPD.

It said it was the first approval by the Japanese Ministry of Health, Labour and Welfare for a maintenance fixed-dose, long-acting dual bronchodilator in a pMDI, also using the Aerosphere delivery technology.

The approval was based on positive results from the phase 3 ‘PINNACLE 4’ trial, which reportedly demonstrated the efficacy and safety of Bevespi Aerosphere in 1,756 patients with moderate to very severe COPD across Asia, Europe and the US, as well as the broader PINNACLE clinical programme involving more than 5,000 patients.

“As the first medicine in its class to be approved in a pressurised metered-dose inhaler in Japan, Bevespi Aerosphere offers an important new treatment option and choice of inhaler device for patients with moderate to very severe chronic obstructive pulmonary disease,” said Mene Pangalos.

Bevespi Aerosphere was already approved in the US, the EU, Canada, Australia and other countries as a dual bronchodilator for the maintenance treatment of moderate to very severe COPD.

The final approval was for AstraZeneca and MSD’s joint development, ‘Lynparza’ (olaparib), which was now approved in Japan as a maintenance treatment after first-line chemotherapy in patients with BRCA-mutated (BRCAm) advanced ovarian cancer, as detected by an approved companion diagnostic test.

AstraZeneca said the approval was based on data from the pivotal phase 3 ‘SOLO-1’ trial, which tested Lynparza as maintenance monotherapy compared with placebo in patients with BRCAm advanced ovarian cancer following first-line platinum-based chemotherapy.

“This approval in Japan is a critical advance for women with ovarian cancer and a BRCA mutation,” said Dave Fredrickson, executive vice-president of AstraZeneca’s oncology business unit.

“The goals of front-line therapy are long-term remission or a cure, yet currently 70% of patients relapse within three years of initial treatment.

“The progression-free survival benefit of Lynparza observed in SOLO-1 represents a major step forward in our ambition to transform patient outcomes.”

Results for the SOLO-1 trial, announced in October last year, showed at 40.7 months of follow-up the median time of progression for patients treated with Lynparza had not yet been reached, compared to 13.8 months for those on placebo.

Lynparza is the only PARP inhibitor approved in Japan.

AstraZeneca said itself and MSD were exploring additional trials in ovarian cancer, including the ongoing phase 3 ‘PAOLA-1’ trial, which was testing Lynparza in combination with bevacizumab as a first-line maintenance treatment for women with newly-diagnosed, advanced, stage IIIB-IV high grade serous or endometrioid ovarian cancer, regardless of BRCA status.

The Japanese approval followed European Commission marketing authorisation announced in June, with interactions with regulatory authorities in the rest of the world said to be ongoing.