Boehringer hails ‘landmark year’ in respiratory

Of the four new products it has launched in 12 months, Boehringer Ingelheim (BI) believes Spiolto (tiotropium/olodaterol) and OFEV (nintedanib) have the potential to be class-leaders, according to Allan Hillgrove, member of the company's board of management.

Indeed, having worked in the respiratory field for 90 years, BI describes 2015 as a landmark year - with new treatments across idiopathic pulmonary fibrosis (IPF), lung cancer and chronic obstructive pulmonary disease (COPD).

And, with the basic patent for Spiolto's forerunner Spiriva (tiotropium) – the company's biggest drug, contributing €3 billion to the coffers in the last financial year - falling off in Europe next year and the US in 2018, BI is clearly pinning its hopes on this coming true.

OFEV is one of these flagship products, a small tyrosine kinase inhibitor for IPF - a challenging orphan disease that leads to permanent scarring of the lungs – which was given a green light in the US in 2014 and in Europe earlier this year.

In 2011 there were no approved treatments for IPF, yet now there are two, in the shape of OFEV and Roche's forerunner Esbriet (pirfenidone), a drug it acquired along with developer InterMune in an $8.3 billion deal last year.

A key element of this hard-to-treat condition is getting earlier diagnosis. With a five-year survival rate "worse than many cancers", Prof Luca Richeldi, University of Southampton, UK, told a press conference at the European Respiratory Society (ERS) congress that OFEV has been shown to almost halve the decline in forced vital capacity (FVC) across a broad range of IPF patients - including those with concomitant emphysema - consistent with a slowing of disease progression.

Acute exacerbations cut

Data from the IMPULSIS-ON open-label single arm study also demonstrated that baseline use of both anti-acid medication and corticosteroids - common medications given to IPF patients - had no influence on the beneficial effect of OFEV, and no additional safety signals after 40 months' treatment. It is also the only treatment to cut acute exacerbations by 68 per cent, said Prof Richeldi - a critically important statistic as the majority of IPF patients (up to 80 per cent) die within one month of an acute exacerbation.

BI also revealed new data showing Spiolto (a combination of two bronchodilators in one inhaler, tiotropium/olodaterol) resulted in significant improvements in quality of life compared to the current standard of care, Spiriva, and offered a superior improvement in lung function compared to a steroid-containing treatment.

"With no cure for COPD," Prof Dave Singh, University of Manchester, UK, told the meeting, "the focus is on reducing disease progression, increasing lung function and thereby improving quality of life."

With 53 per cent of Spiolto patients witnessing a greater quality of life versus 39 per cent of those given Spiriva – as measured by a 4-point improvement on the St George's respiratory questionnaire – this is the difference in being able to walk up the stairs, do some gardening, or simply not having to stop and rest so frequently, he said, adding that maintaining these activities of daily living is important in breaking the downward spiral of the disease.

New data such as these are starting to make pulmonologists think that it's best to start treatment with two bronchodilators earlier on in the disease, rather than wait until it progresses to the moderate or severe stages, Prof Singh added. Clearly the ambition is for Spiolto to become a first-line maintenance therapy in COPD.

"There is substantial overuse of inhaled corticosteroids [ICS] early in the management of COPD," explained Prof Kai-Michael Beeh, INSAF Respiratory Research Institute, Germany, which are widely used outside treatment guidelines in patients with less severe COPD and low exacerbation risk, as well as being associated with significant systemic side effects, including osteoporosis. New data from the ENERGITO trial, also presented at the ERS congress, showed significant improvement in lung function with Spiolto versus the steroid-containing therapy salmeterol/fluticasone, adding to the weight of evidence questioning whether the benefit of ICS outweighs their risks.

The challenge now for BI is to get both OFEV and Spiolto through reimbursement and on to physicians' radars. "It's early days for both launches," Hillgrove revealed, "but the number of patients being treated with OFEV is already greater than anticipated."

This is good news for the company, which is having to play catch-up to Esbriet; in the first half of this year Esbriet generated sales of 229 million Swiss francs (CHF) ($234 million) and is predicted to become a CHF 2 billion drug.

The situation with Spiolto is perhaps a little more challenging in terms of demonstrating that the additional benefit over Spiriva - the current standard of care - is worth the cost.

When asked if BI would consider developing its own generic version of Spiriva, Hillgrove told pharmaphorum that a number of different commercial models had been evaluated but the company had decided not to pursue this route and was putting all its weight behind Spiolto, with a "comprehensive real-world data plan" in the offing designed to demonstrate the positive societal benefit of early, and long-term, treatment of COPD on patients' lives.

And BI clearly has no plans to rest on its laurels in respiratory, with eight compounds in the pipeline stretching from pre-clinical through to phase II in areas including severe asthma, interstitial lung disease, cystic fibrosis, and acute respiratory distress syndrome, Hillgrove explained to pharmaphorum. The firm is also buoying up its ambitions for OFEV with a trial in systemic sclerosis, a rare autoimmune disease resulting in abnormal growth of connective tissue and leading to vascular damage and fibrosis.