ERS - Novartis' indacaterol laying groundwork for combination success

As physicians are increasingly harbouring doubts about the usefulness of inhaled corticosteroids to treat COPD, bronchodilators are becoming more firmly recognised as the best weapon developed so far to treat the lung disease. And as drug companies develop ever more potent bronchodilators, the hope is that even greater relief of patients’ symptoms can be achieved by combining therapies with different modes of action.

This was a key message that emerged from the European Respiratory Society meeting this week, and from the many sessions calls could frequently be heard for more research into combination approaches. A commonly used analogy used was cardiology, where ACE inhibitors added to diuretics are now widely and very successfully used to control blood pressure. One such treatment in development which, if successful, could answer those calls is Novartis’ QVA149, and phase II data presented yesterday underlined the potential in this product.

The drug is a combination of Novartis’s indacaterol (QAB149), a new once-daily long-acting beta agonist (LABA), and a novel once-daily long-acting muscarinic antagonist (LAMA) called NVA237, licensed from Vectura and Sosei. In the phase II trial QVA149 demonstrated an impressive improvement in lung function over both placebo and indacaterol alone, over seven days.

“The data generated buzz amongst experts at the conference, particularly given the incremental benefit over indacaterol, and there was anecdotal evidence from investigators that patients experienced a clear benefit from using QVA149 rather than monotherapies,” Stefan Hamill and Chirag Talati, analysts at Noble, wrote in a research note today.

Gold standard

They believe that QVA149 is positioned as a future “gold standard” for COPD treatment, a bold prediction for a mid-stage product and a position no doubt reinforced by highly encouraging data for indacaterol, which itself is creating much excitement.

Many doctors and analysts believe indacaterol has best-in-class potential and new data released at the conference underlined its potential as a monotherapy. A 26-week trial found that patients had significantly improved lung function and reduced breathlessness over the blockbuster COPD drug Spiriva, which is viewed as one of the best bronchodilators available.

Previously, longer-term studies with indacaterol have found that certain patients displayed little deterioration in a key measure of lung function over a year, a highly clinically relevant finding considering no agent has yet been found to check the degenerative disease. This impressive duration of action, plus very fast onset and once-daily dosing, which would help with compliance and itself contribute to the drug’s efficacy, has created much excitement around indacaterol, and the drug represents the cornerstone of Novartis' stride into the COPD field (Novartis’ COPD data could puff up respiratory franchise, May 21, 2009).

Consensus sales forecasts for 2014 currently sit at $257m, according to EvaluatePharma, although this figure appears to have considerable potential for upgrade should the approval process go smoothly. The drug is already in front of regulators and should hear in Europe before the end of the year, a possibly by the end of October in the US.

Combination push

Novartis funded a two-hour evening symposium at the ERS highlighting the potential of indacaterol, a high profile event that was no doubt laying the groundwork for a significant marketing push. The presenting physicians made a strong case for bronchodilation as the corner stone for COPD therapy, and stressed the added benefits presented by potent, once-daily therapies. They also pushed the theory that combining drugs with different mechanisms of action could generate even better outcomes, all of which neatly rolled into the phase II QVA149 data the next day.

The commercial potential for a once-daily LABA/LAMA combination is certainly high, a recent analysis by EP Vantageshowed (Therapeutic focus - COPD market looking for the daily dose August 13, 2009). The data so far is highly encouraging, however, whether QVA149 will fulfil that dream remains to be seen; its component parts will have to succeed on their own first. Indacaterol is almost there, but the LAMA component, NVA237, only entered phase III a month or so ago and data will not be available until 2011.

Still, with physicians increasingly calling for combination approaches to treat COPD, the focus on projects like QVA149 is likely to grow. This will happen not only with bronchodilation, the excitement around Nycomed’s Daxas (roflumilast), an anti-inflammatory with an entirely different mode of action, was also largely down to physicians believing they have another option to incrementally improve the symptoms of patients (Vantage Point - Daxas finds fans among doctors at ERS, September 14, 2009).

There is no cure for COPD and the progressive disease gradually erodes a patient’s quality of life, the exacerbation events carry a similar mortality risk to heart attack. Until a way is found to arrest and possibly even reverse the course of the illness, combining all the weapons possible to achieve maximum impact will be a key focus for research in the future.

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