Inhaled triple therapy: who’s bothering?

Inhaled triple therapy: who’s bothering?

March 03, 2016

Inhaled triple therapy: who’s bothering?

In their search for the next blockbusters and in the context of a lack of therapy breakthrough against Asthma and COPD, pharma companies are pursuing triple combination therapy as the next revenue generator. Triple therapy for Asthma and COPD is understood to be the simultaneous dosing of a fixed combination of 3 molecules; these usually are ICS (inhaled corticosteroid) + LABA (long acting beta agonist) + LAMA (long acting muscarinic agonist). The evidence on the benefits of triple therapy is still being debated (2015), with some recent clinical practice suggesting that the removal of the ICS component does not lead to a worsening of symptoms (2014). The main issue seems the lack of ability to decide when to step up or step down triple therapy (2015). Nevertheless, a number of players are moving ahead with their triple therapy projects, and here are the ones in the race:

Developer  Molecules  Dosage  Stage  Code name
GSK / Theravance  FlF, UM, VI  DPI Phase III  
AZ / Pearl therapeutics BUD, FF, GPB   pMDI Phase III PT010
Novartis / Vectura  IND, MF, GPB  DPI  Phase III  QVM149
Circassia  GPB, FP, SX pMDI  Phase I  PSX3001
Chiesi  BDP, FF, GPB  pMDI  Phase III  CHF5993
CIPLA CIC, FF, TIO  DPI  Marketed in India  Triohaler Rotacaps

API abbreviations:
BUD Budesonide; BDP Beclomethasone DiProprionate; CIC Ciclesonide; FF Formoterol Fumarate; FlF Fluticasone Furoate; FP Fluticasone Proprionate; GPB Glycopyrronium Bromide; IND Indacaterol; MF Mometasone Furoate; SX Salmeterol Xinafoate; TIO Tiotropium; UM Umeclidinium; VI Vilanterol.

What is the market for fixed triple combinations?
How big is the market for triple therapies for asthma and COPD? GSK is reported to estimate that about 18 to 20% of COPD patients already take a 2+1 combination (2015). This equated to a $3b sales segment of 2+1 therapies (LAMA+LABA/ICS for COPD) in 2013. Some analysts predict that GSK sales of a fixed triple combination might peak at $250M in 2020, out of a potential market of $3.4b (2016).

Is there any point in triple therapies?
The main benefits of triple therapy are:
-improved lung function, dyspnea and quality of life. These improvements are statistical but have not reached clinical importance (2015)
-reduction of hospitalisations for severe/acute COPD exacerbations.
-once daily treatment (true for GSK’s but not Chiesi’s product)
-improved patient compliance
However, these benefits do come at the cost of a triple therapy, and new MABAs compounds developed at AstraZeneca could well challenge the need for triple therapies and make them redundant.

As if a triple therapy was not complex enough, some clinicians in Spain have tried a quadruple therapy: roflumilast + LABA/ICS/LAMA (2015) … hold on tight!

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