GlaxoSmithKline might be no closer to acquiring Theravance than it was a year ago, but it is certainly not taking its foot off the gas as far as using the companies’ alliance to drive its post-Advair respiratory disease strategy.
It secured US approval of Anoro in December, and is now moving swiftly on to run a massive phase III study of the first ever triple combination of its type in chronic obstructive pulmonary disease (COPD). The dual combo market is starting to see competition from generic and novel products, so it is hardly surprising that Glaxo wants to stay ahead of the game.
Anoro was the first ever combination of a long-acting beta agonist combined with a long-acting muscarinic antagonist to get US approval. Earlier approval had been secured for the Relvar/Breo, which, as a LABA/steroid combo, mimics the mechanistic approach of Glaxo’s blockbuster Advair and several other respiratory drugs.
One step further
But Impact, the phase III trial just launched, takes things a step further, combining the three separate constituents of Relvar/Breo and Anoro into a single fixed-dose combination delivered through the Ellipta inhaler that is used with both dual combo products.
The double-blind study will seek to enrol some 10,000 COPD patients and randomise them to one of three once-daily doses: the first will test a combo of fluticasone, umeclidinium and vilanterol dosed at 100mcg/62.5mcg/25mcg respectively, the second Relvar/Breo and the third Anoro.
The primary efficacy measure is the annual rate of moderate and severe exacerbations, and this makes up two co-primary endpoints, one comparing the triple combo versus Relvar/Breo and the other versus Anoro. The trial is powered to show superiority over the dual combo products, Glaxo said.
Impact is expected to end in mid-2017, and no interim readouts are expected before then. Glaxo is the study’s sole sponsor, so presumably it is also footing the entire cost, with no contribution from Theravance.
Under a long-standing alliance Glaxo pays its biotech partner a royalty on sales of all three products. Theravance retains a 15% economic interest in the Glaxo payments on the triple combination, with the remaining 85% accruing to Theravance Biopharma – a spin-out of Theravance that is focusing on the group’s development assets.
Monopoly – but for how long?
While the triple approach marks the first ever combination of a LABA, LAMA and steroid to enter phase III, Glaxo and Theravance will not have this space to themselves for much longer.
PT010, a combination of the same three mechanisms of action, was acquired by AstraZeneca through the UK company’s $1.15bn takeover of Pearl Therapeutics last year, and is in phase II. Astra is keen to move quickly, and entry into pivotal trials is unlikely to be far off (Astra’s Soriot finds hidden value in private assets, June 10, 2013).
Little is known about the other key players in this space. Novartis, which has an approved LAMA/LABA combo, Ultibro Breezehaler, is understood not to be interested in a triple combo, Bryan Garnier analysts wrote today.
Boehringer Ingelheim, meanwhile, is awaiting US approval of the LABA Striverdi Respimat, with a view to combining this with its blockbuster LAMA Spiriva. The private German group has said nothing about a possible triple combo, though it rarely discloses information about projects before they enter late-stage testing.
Relvar/Breo and Anoro are expected to reach sales of $1.8bn and $2.7bn respectively in 2020, and much of this depends on how the competitive landscape pans out. In addition to the likes of Novartis and Boehringer, Glaxo faces the threat of generic versions of Seretide, which have already arrived in Europe.
The pricing and efficacy of future products will be of vital importance, but success with a triple combination could give Glaxo a strong advantage.
|Impact||10,000 patients, three-arm, randomised, double-blind, phase III||NCT02164513|