Growing IPF drugs market evident at ERS Congress

pharmafile | November 3, 2014 | Feature | Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing |  ERS, Esbriet, IPF, elf, european respiratory society, ofev 

Arriving in Germany for this year’s European Respiratory Society (ERS) International Congress 2014, what awaited Pharmafile at the Ausgang was an eye-opening insight into the world of lung disease.

The city of Munich, home of the Bavarian city symbol the Frauenkirche church, and of course Oktoberfest, played host to the ERS’ 24th week-long annual meeting.

Founded in London in 1990 the ERS comprises some 10,000 members across 100 countries, and its aims are to promote lung health through research and education. Covering both basic science and clinical medicine, the Switzerland-based body also publishes academic journals and monographs.

Originally formed with the merger of the Societas Europaea Physiolgiae Clinicae Respoiratoriae and the European Society of Pneumology, the ERS is made up of medical professionals and scientists working in the area of respiratory medicine.

With over 22,000 registered delegates, the ERS Congress is the world’s biggest respiratory meeting, and includes discussions such as the use of unregulated e-cigarettes – which the organisation announced it opposes.

The ERS says that “while the short-term negative impact on health appears not as great as tobacco cigarettes, the long-term effects of e-cigarettes are not known”. The event hosts a variety of stands with various companies all pushing their latest ‘groundbreaking’ respiratory treatments, alongside free tea and coffee.

Also available for the fourth year in a row was an interactive smartphone app giving users the chance to search by room, time, speaker and disease group, featuring floor-plans, exhibitor lists and maps.

To give a snapshot of the event floor – Orbicel was promoting its new Salmex inhaler (fluticasone and salmeterolum). The Polish company asked delegates to ‘enter a new orbit,’ on its space-age stand and find out more about the first inhaler in the world to have user instructions on a label – directly on the side of the device.

Raising awareness

Annually, respiratory disease contributes to one million deaths and costs around €380 billion in Europe, with half of all these deaths caused by smoking.

“What is always astounding is the size and scale of respiratory disease – the number of conditions that are included under this umbrella and the impact that this has on people’s quality of life and life expectancy,” says Pippa Powell, head of the European Lung Foundation (ELF).

Founded by the ERS in 2000, ELF aims to bring together patients, the public and respiratory professionals to positively influence lung health. At this year’s congress ELF was very much focussed on the launch of its new ERS/ELF Healthy Lungs for Life campaign.

Powell tells me: “This year we are focussing on the theme Breath Clean air and we’re absolutely delighted with the impact the campaign is having at the congress.”

The organisation’s campaign aims to educate all respiratory stakeholders about the importance of lung disease and the value of lung health. Pharmafile tried out ELF’s ‘Clean air and lung health quiz’ and scored a respectable eight out of ten.

Also faring well in this area were the World Health Organization (WHO), as it was during the congress that the group were presented with the annual ELF award for improving the lung health of millions of people by providing outdoor air quality guidelines.

Accepting the award for WHO was its regional director for Europe, Zsuzsanna Jakab, who said: “It is a great pleasure and honour for me to accept the 2014 ELF award for WHO’s work in improving respiratory health.”

WHO produced its first set of air quality guidelines back in 1987, and it says air pollution was at the root of seven million premature deaths in 2012, with 3.7 million of these being connected with poor outdoor air quality.

Jakab says: “While we guide the design of effective measures and policies, the health sector must reach out, convincing policy-makers for transport, energy, agriculture, urban and land management to act appropriately, and improve the health and well-being of our citizens.”

Asthma, tuberculosis and chronic obstructive pulmonary disease (COPD) are of course also types of respiratory disease, with the latter affecting over three million people in the UK every year. So it was no surprise that Novartis was in Munich to present data for example, showing that its COPD drug Ultibro Breezhaler (indacaterol/glycopyrronium) was superior in reducing flare-ups when compared to GlaxoSmithKline’s blockbuster drug Seretide Accuhaler (fluticasone/salmeterol).

The LANTERN study, which put the two drugs toe-to-toe, found that Novartis’ once-daily offering Ultibro was better in reducing exacerbations and improving lung function compared to twice-daily Seretide from GlaxoSmithKline.

Speaking at the congress Vasant Narasimhan, head of development at Novartis, said that the results “provide further evidence of the potential of Ultibro to deliver better exacerbation reduction and improvements in lung function, compared to the current standard of care”.

Idiopathic pulmonary fibrosis

Part of the reason Pharmafile attended the congress was to find out more about the poorly-diagnosed idiopathic pulmonary fibrosis (IPF) disease, which typically affects male former smokers.

Idiopathic, or ‘cause is unknown’, belongs to a large group of more than 200 respiratory diseases known as interstitial lung disease. With symptoms such as scarring of the lungs and shortness of breath, diagnosis of this disease can often be challenging. IPF is known to trigger clubbing of the digits and cause a crackling sound in the lungs when breathing.

Half of all people with IPF are initially misdiagnosed, as the disease can look like other conditions – such as ageing, cardiac disease, or emphysema.

Pharmafile caught up with the head of ELF to discuss its plans for 2015, and how IPF is to be addressed. Powell tells us: “With regards to IPF – we have been working with a number of patient groups across Europe to include the patient voice in a current project to review the 2011 ERS IPF guidelines.”

She continues: “Focus groups have been held in Ireland, Italy, Belgium, Germany, and the UK to identify the diagnosis and management needs of patients and carers. Leading experts in IPF will give a response to these needs, and incorporate them into the final document, due for publication in 2015.”

One company among the handful that have sought to tackle the disease is InterMune, who at the event announced positive data for its Esbriet (pirfenidone) – the first IPF treatment to gain approval in the EU.

Results of InterMune’s Phase III trials found that the drug significantly reduces decline in lung function and also improves patients’ mobility. The treatment however, did fail to meet its secondary endpoint of dysphnea (shortness of breath).

“These results support the treatment’s effect of up to 72 weeks with evidence of a sustained durable effect,” says Professor Paul Noble who hails from the Cedars-Sinai Medical Center in Los Angeles. “The observations provide further support for a favourable benefit risk profile of Esbriet in patients with IPF.”

Whilst gaining its European approval in 2011, the lung-scarring drug has had a much more trying time attempting to gain a nod in the US, when the FDA knocked back the treatment in the same year – but it received positive news in October when the FDA finally approved it for IPF.

Noble says that “coupled with the long-term safety data presented at this meeting, these results will further inform clinical decision making by healthcare practitioners involved in the care of patients with IPF”.

Pricing pressure

InterMune, whose finances were recently boosted by an $8.3 billion takeover by Roche, saw sales of $35.7 million in the three months ending June this year, verses $14.4 million the year before.

Giacomo di Nepi, executive VP and managing director for the firm in Europe, says: “Our contribution to the disease has been to provide the first therapy, but also to add help to what has been done in getting a better knowledge of the disease and the way to approach it.”

According to energy and healthcare analysts GlobalData, IPF therapy sales across the US, France, Germany, Italy, Spain, and the UK are set to rise from $49 million in 2012 to over $1.1 billion by 2017.

Also at the congress with announcements to make was Boehringer Ingelheim, a close rival company to InterMune in the field, and offering an IPF treatment of its own via the orphan drug Ofev (nintedanib).

The medicine, like its rival Esbriet also gained FDA approval in October. The firm says that Ofev slowed lung function decline independent of severity of pulmonary inactivity impairment at baseline. The Phase III trial also showed that Ofev reduced the proportion of patients with IPF who experienced disease progression.

Speaking at the congress was Dr Susanne Stowasser, the global team leader of medical affairs at Boehringer who said: “The results of these analyses further confirm and support the efficacy of nintedanib on slowing disease progression in a wide range of patients with IPF.”

Ofev is expected to be priced at a 25% premium to Esbriet, and the company told Pharmafile it is “committed to making nintedanib available to patients with IPF”.

Now that both drugs are approved in the US they should turn into lucrative products for the firms, as the IPF therapeutics US market is predicted to grow from $6.5 million in 2012, to $696 million in 2017.

“The launch of Esbriet and nintedanib to a [US] market that previously had no therapeutic option will cause the market to experience exponential growth,” says Dr Samantha Fernando, GlobalData’s analyst covering immunology in the forecast.

“In contrast, the European IPF market was valued at a far stronger $43 million in 2012, but is forecast to grow to $419 million in 2017.”

Both InterMune and Boehringer have provided their drugs for compassionate use in an expanded access programme in the US. This is a platform used in select instances to provide early access to drugs for patients suffering from a fatal disease, who have no alternative option.

On 15 July 2014, Esbriet received a ‘Breakthrough Therapy Designation’ by the FDA, and in fact Ofev obtained the same designation the very next day. So far, being the only two pharma firms to produce an IPF therapy treatment, they are competing in a rather niche market which is set to grow over the next decade.

Esbriet’s recent FDA approval will give the US biotech company the upper hand – what with its recent Roche deal and an already reported $40,000 annual revenue per patient in the EU and Canada for its medicine.

Boehringer’s IPF drug on the other hand also has potential in oncology, after the EMA recently issued a positive opinion for its approval in combination with docetaxel for the treatment of lung cancer.

A recent trial showed that adding nintedanib extended the median overall survival from 10.3 to 12.6 months in patients. Along with this, the drug is also undergoing Phase III studies for the treatment of forms of colon and ovarian cancer, as well as Phase II trials in mesothelioma, kidney and lung cancer.

The German firm recently announced incidentally it will be paying up to $600 million for CureVac’s CV9292 cancer vaccine, which reported net sales of around $18.1 billion in 2013.

Prior to the drug’s October approval announcement, a Boehringer Ingelheim representative at the congress told Pharmafile that indeed the firm was hopeful of Ofev’s possible approval in the US and Europe in 2014, or 2015.

The company did need a morale boost, as earlier this year the firm announced it was cutting around 600 jobs in Germany as part of a drive to reduce costs by €450 million. According to Boehringer, this is due to both healthcare budget cuts in the US and the AMNOG drug pricing scheme in Germany.

On a more positive note, Boehringer also revealed it is expanding its oncology pipeline with clinical studies for colorectal cancer and volasertib in acute myeloid leukaemia. 

Other companies looking at entering the IPF market include Gilead Sciences, which is exploring the use of its simtuzumab in a subgroup of fast-progressing patients; Biogen Idec, which has a candidate called STX-100 in Phase II; plus Bristol-Myers Squibb and Fibrogen who also have compounds in early- to mid-stage developments.

Living with the condition

Pharmafile met for a discussion with Don Wooton, a 69-year-old retired civil engineer from Surrey, who two years ago was diagnosed with IPF.

He told us what it’s like to live with the disease – he says he lives a fairly normal life but one with its obvious limitations. He walks, plays golf three times a week, but avoids the steep hills.

“For now, with my current medication my condition remains steady and stable, and although I’m aware that there can be triggers that can change my situation I’m happy under my present condition,” says Wooton.

Treated with Esbriet for the first time in 2013, he explains that he has nothing but praise for the medical team involved since he first reported the tightness in his chest two years ago.

Each IPF patient follows a different, unpredictable course. As IPF is a progressive disease, patients’ respiratory symptoms become worse over time. It is not possible to predict if the disease will progress slowly or rapidly, or when the rate of decline may change.

Looking to the future Wooton tells us that his consultant has told him to explore options, and that he’s not particularly hopeful due to the NHS’ 65-years and over cut-off point for transplant patients.

Wooton is even pondering his options abroad as other countries consider the physical age over the chronological age. And with a disease such as IPF, this is a worrying concern for many patients who are diagnosed in later life, as the majority are.

He concludes: “I’ve not joined any support groups; I don’t feel at this time in need of that sort of support. I remain positive, and consider my glass half full, not half empty.”

This year’s ERS Congress in Munich has certainly emphasised the need for commitment to R&D and education in respiratory disease.

New breakthroughs such as Esbriet and Ofev, will not only benefit patients diagnosed with a chronic disease but they will also help widen a lesser known market and contribute to new findings, and perhaps a bigger understanding and eventual cure of idiopathic disease.

Tom Robinson

Pharmafile’s accommodation and flights for the event were paid for by InterMune