Rare diseases – pharma’s new frontier
pharmafile | March 26, 2012 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing | Big Pharma, CAPS, McConaghie, rare diseases
The last ten years has seen our understanding of rare diseases move ahead rapidly, often thanks to greater understanding of genetic problems, which are behind 80% of rare diseases.
For the pharma and biotech industry, this has made rare diseases an increasingly important area for research – and this is matched by the commercial potential.
Another factor influencing the industry’s move towards rarer diseases is the fact that breakthroughs in the most widespread problems – hypertension or asthma for example – have become harder to achieve.
In terms of drug discovery and development, rare diseases present particular opportunities for researchers. Patrick Vallance, senior vice president of medicines discovery and development at GSK, commented on the field when the company launched its rare diseases division in 2010.
“The risk associated with product discovery and development in rare diseases is generally lower than other disease areas as disease definitions are very clear, and clinical trials tend to be small with robust endpoints,” said Vallance. “In most cases the molecular target is known, making it easier for specialised physicians to diagnose patients”.
A good example of just how significant breakthroughs in rare diseases can be is in cystic fibrosis. Genzyme’s Pulmozyme, launched in 1993, significantly improved the quality of life of patients, and greatly extended life expectancies – it has contributed to cystic fibrosis patients now typically surviving into their thirties. (See below for Vertex’s new breakthrough in the disease).
Recent years has seen an explosion in the number treatments coming onto the market for rare and ultra-rare conditions. But these drugs are not without their controversies – treatments such as Shire’s Elaprase for Hunter’s Syndrome and Genzyme’s Myozyme for Pompe Disease have helped address previously untreatable diseases, but are extremely expensive.
Alexion’s Soliris, at $409,500 a year, is the world’s single most expensive drug. This monoclonal antibody drug treats a rare disorder in which the immune system destroys red blood cells at night. The disorder, paroxysymal nocturnal haemoglobinuria, affects just 8,000 Americans. Alexion earned $783 million from Soliris last year, an increase of 45% on 2010.
As more and more treatments reach the market, it is raising questions about the sustainability of paying for these medicines. At the same time, there are many rare diseases that are still without adequate treatment.
When added together, the sum of patients with rare diseases is very considerable – 5,000-7,000 rare diseases have been identified to date, affecting 30 million Europeans today.
Rare disease is defined differently around the globe. In the US, a disease is rare if it affects fewer than 200,000 people, which means that around 30 million Americans are afflicted with rare diseases.
In Europe the definition is slightly broader, considering a disease as rare when it affects no more than 5 in 10,000 people in EU – equivalent to around 250,000 people or fewer for each disease.
The US Orphan Drug Act (ODA) of 1983 has been the single biggest catalyst for encouraging research, and more than 390 orphan products for treatment of rare diseases have been approved by the FDA since the legislation came into effect. EU legislation followed in 2000, and has also helped incentivise research.
Rare Disease Day
Patient groups with an interest in rare diseases are now coming together to promote awareness, research investment and improvements in how health systems diagnose and treat rare diseases. This year saw 29 February designated as Rare Disease Day around the world, with researchers, regulators and the industry all raising awareness of the need for more research.
Rare Disease Day is co-ordinated by the European Organisation for Rare Diseases – EURORDIS, a federation of more than 500 rare disease patient organisations in 46 countries. The campaign involves rare disease groups in 60 countries including the EU, the US and Canada, Russia, Brazil, Argentina, Australia, Japan and China.
Commenting on the day, EU commissioner for health John Dalli said: “With so many of our citizens affected, rare diseases are by no means a rare or marginal problem. Our first task has been to bring together the scarce resources that are currently fragmented across individual EU countries and to spark off joint action to help patients and professionals share expertise and information across borders.” Commissioner Dalli said the EU could help ensure that enough funding is being made available for the rare disease research.
The US regulator the FDA also took part, and on 1 March its ‘FDA Rare Disease Patient Advocacy Day’ looked to engage and educate the rare disease community on regulatory processes related to rare diseases.
Integrating rare diseases into the big pharma business model
While rare diseases are clearly an area that big pharma wants to have a presence in, the companies know that expertise in this area is different to the ‘mass market’ pharma business. To that end, the big companies have either acquired specialists – with the aim of keeping them semi-autonomous – or have set up new rare diseases business units from scratch.
Pfizer established its rare diseases business unit in June 2010. Jose Carlos Gutierrez-Ramos, senior vice president, biotherapeutics R&D, commented at the time: “We are coupling Pfizer’s existing experience in rare diseases, such as haemophilia, with our advanced protein technologies, resources and world-class scientific team.” The unit is led by Edward Mascioli, and is based in Cambridge, Massachusetts and reports to Gutierrez-Ramos.
Mascioli is the founder of Dapis Capital, a private equity firm focused on life sciences, and was previously vice president of clinical affairs at Peptimmune and senior medical director at Paraxel. Pfizer’s unit will look at treatments across all therapeutic areas and the company wants to work closely with patient advocacy groups. It has just filed a new treatment for a rare neurodegenarative disease with the FDA.
GlaxoSmithKline established its rare diseases unit ahead of Pfizer, setting its division up in February 2010. Marc Dunoyer, GSK’s president of Asia Pacific and chairman of Japan leads the new operation, working closely with Patrick Vallance. The unit is now working to leverage existing capabilities and partnerships and establish further in-licensing opportunities.
Marc Dunoyer said: “In addition to our existing discovery effort, alternative opportunities need to be explored to make treatments available for rare diseases. This complementary approach will combine our existing global expertise with specialist partners. Over time, this new unit has the potential to deliver multiple therapies responding to high medical needs of underserved populations of patients.”
Vallance added: “The entry into this new therapeutic area forms part of GSK’s strategy to deliver more products of value and improve returns in R&D through a focus on areas with a higher probability of success.”
GSK entered into strategic collaborations with Prosensa and JCR Pharma in 2009. The alliance with Prosensa is set to develop new therapies in correcting gene expression in diseases with large unmet medical needs. The agreement with JCR has seen GSK obtain global rights to a number of enzyme replacement therapies that have the potential treat several orphan diseases.
Meanwhile, Novartis has developed its own dedicated research organisations, collaborations and financing mechanisms to help address the needs of patients with rare diseases. The Novartis Institutes for BioMedical Research (NIBR), is actively targeting rare diseases where there is clear understanding of the disease’s underlying cause, and where there is real unmet medical need.
An example is Muckle-Wells syndrome, a rare disease with potentially fatal complications. This syndrome is part of a group of auto-inflammatory diseases called cryopyrin-associated periodic syndrome (CAPS). Novartis developed the first treatment option for the 6,000 patients worldwide affected by CAPS.
Roche is using its biologics expertise, especially through its subsidiary Genentech, to make in-roads in the rare diseases field. In April 2011 Roche and Biogen Idec gained US approval for the use of Rituxan/MabThera (rituximab), in combination with corticosteroids, as a new medicine for adults with Wegener’s Granulomatosis (WG) and Microscopic Polyangiitis (MPA).
WG and MPA are two severe forms of vasculitis called ANCA-Associated Vasculitis (AAV), a rare autoimmune disease that largely affects the small blood vessels of the kidneys, lungs, sinuses, and a variety of other organs. Both WG and MPA are considered orphan diseases with an estimated prevalence in the US of approximately three cases per 100,000 people.
Sanofi and Genzyme
In 2011, Sanofi acquired Genzyme for over $20 billion, one of the long-term leaders in rare disease treatments. Three of Genzyme’s key drugs include Fabrazyme for Fabry’s disease, Cerezyme for Gaucher disease and Aldurazyme for Mucopolysaccharidosis I. All three drugs treat rare conditions that come from a deficiency in certain enzymes.
Sanofi is hoping that this integration will help shore up its future, and it seems to be having the desired effect – analysts predict that Sanofi will become the world’s biggest pharma company by revenue this year, thanks in part to the Genzyme integration, and is set to stay there for the foreseeable future.
Sanofi moved to buy Genzyme after contamination at the firm’s Allston manufacturing plant meant its production levels of Fabrazyme and Cerezyme dropped significantly. The resulting shortage of both drugs allowed its rival Shire to capitalise on Genzyme’s woe, as its Gaucher disease drug Vpriv took considerable market share from Cerezyme.
UK rare diseases strategy
The growing profile of rare diseases clearly requires a response from healthcare systems round the world, which are very much geared to treating the most common diseases. The UK government has just launched its first ever strategic plan for the treatment of rare diseases. The Department of Health launched a consultation on the topic on 29 February, with the aim of improving how the range of diseases are treated on the NHS.
The consultation makes a number of recommendations:
• recommends using specialist centres to make exact diagnosis – this will make sure people are treated earlier and in some cases this could save lives;
• acknowledges that all doctors should have the right training to be aware of the possibility of a rare disease; and
• recommends that the care of patients with rare diseases should be better co-ordinated.
The government says better co-ordination of care could help improve care for patients. For example, the national service for patients with epidermolysis bullosa, an inherited skin condition, provides a ‘one stop shop’ so that patients do not have to make separate visits to see the dermatologist, dietician, chiropodist and dentist etc. This saves patients time and money by avoiding multiple visits to different clinics and hospitals.
Health minister Lord Howe said: “The UK has a good story to tell about supporting and treating people with rare diseases. But we know the challenges people face and that there is always room for improvement.
“This is the first time the UK has had a coherent set of proposals on rare diseases which outlines how we can build on our strengths through improved co-ordination of services, stronger research and better engagement with patients and their families.
“These proposals will benefit patients and help the NHS to be more efficient and co-ordinated, as well as save money. A recent unpublished study has shown that better care of patients with rare neuromuscular diseases could save the NHS £31 million per year by avoiding emergency admissions.”
Advances in pharma science mean rare diseases treatment will continue apace over the coming decades. But as with more common conditions, healthcare systems around the world will be seeking the kind of savings outlined above in order to justify increased investment in new and expensive treatment for rare diseases.
Andrew McConaghie
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