FDA rejection scuppers AZ’s hopes of a COPD triple clash with GSK

The FDA has just handed an advantage to GlaxoSmithKline’s triple therapy for chronic obstructive pulmonary disease (COPD) by rejecting AstraZeneca’s PT010, a close competitor.

AZ has confirmed that the US regulator issued a complete response letter (CRL) for PT010, a triple therapy for COPD that would compete with GSK’s already-marketed Trelegy.

A spokesman for AZ told Pharmaphorum that the CRL “states that more clinical data are required to support the application” but that the company has additional data in hand ready to be submitted which will “further characterise PT010’s strong clinical profile.”

PT010 is based on the inhaled corticosteroid budesonide, long-acting muscarinic antagonist (LAMA) glycopyrronium and long-acting beta agonist (LABA) formoterol fumarate, and has been filed for approval based mainly on the results of the KRONOS trial. It has already been approved in Japan as Breztri and is under regulatory review in Europe and China.

In KRONOS, PT010 achieved statistically significant improvement in eight of nine lung function goals in patients with moderate to severe COPD.

“We will work closely with the FDA regarding next steps, including submitting for review recent results from the second positive phase 3 trial, ETHOS, which was not completed at the time the [New Drug Application] was submitted,” said the spokesman.

ETHOS went a step further than KRONOS as it looked not just at lung function but also at the rate of COPD exacerbations – a sudden worsening of symptoms that can often lead to hospitalisation.

The FDA has form on this issue, rejecting GSK’s IL-5 inhibitor Nucala (mepolizumab) last year for COPD because it felt that the data on exacerbations wasn’t strong enough.

Trelegy – based on corticosteroid fluticasone furoate, LAMA umeclidinium and LABA vilanterol and approved in 2017 – is central to GSK’s efforts to replace its COPD blockbuster Seretide/Advair (salmeterol/fluticasone propionate), which has lost patent protection and seen revenues slide to around $1.1 billion in the first half of the year, well down from its $8 billion-a-year peak.

Trelegy isn’t yet close to scaling those heights, with sales coming in at around $250 million in the first half of the year, although it is growing fast and GSK recently reported new data in uncontrollable asthma that could inject further momentum if approved.

Analysts at Jefferies have previously predicted $1.5 billion in sales at peak for Trelegy, mostly from COPD but with asthma contributing a portion of that total.

It already competes with a triple COPD therapy from Chiesi called Trimbow (beclomethasone/glycopyrronium/formoterol) which was approved in 2017. It is delivered twice-daily, versus once-daily for Trelegy. Privately-held Chiesi doesn’t publish sales data for individual products in its portfolio.