Companies face mixed fortunes in ultra-orphan approvals
pharmafile | November 26, 2015 | Feature | Medical Communications, Research and Development | BioMarin, Duchenne Muscular Dystrophy, FDA, Genzyme, NICE, ultra-orphan drugs
UK regulator NICE has recommended Vimizin, a drug for a very rare genetic disorder, after the manufacturer and NHS England agreed a managed access scheme.
But the manufacturer, BioMarin Pharma, faces an uphill struggle for approval for another ultra-rare disease drug, Kyndrisa (drisapersen) in the US, after the FDA published a damning critique of its efficacy. Bosses at two rare disease rivals, Genzyme and Actelion, have spoken out at their frustrations in their dealings with regulators and the ongoing ultra-orphan drug pricing debate.
In final draft guidance as part of its Highly Specialised Technologies programme, NICE provisionally approved Vimizin (elosulfase alfa) for the treatment of a rare inherited lysosomal storage disease, when used as part of a managed access agreement – which NICE had called for in its draft guidance.
Vimizin treats mucopolysaccharidosis type IVa (also known as MPS IVa and Morquio A syndrome), a life-limiting disease that affects around 88 people in England. People born with the disease lack an enzyme – called N-acetylgalactosamine-6-sulfatase – that breaks down large sugar molecules (glycosaminoglycans) that the body cannot use.
The resulting build-up of glycosaminoglycans in the body causes a wide range of symptoms that typically appear in early childhood and worsen over time. These include joint and skeletal abnormalities, hearing and vision loss, heart valve disease, pain, fatigue, and progressive loss of mobility.
The average life expectancy in people with MPS IVa is about 25 years – primarily because of respiratory failure and heart problems (63% and 15% of deaths respectively).
Vimizin replaces the enzyme lacking in people with MPS Iva, and provides a previously non-existent treatment option for the underlying disease, which currently also lacks a standard pathway of care.
Commenting on the draft guidance, Meindert Boysen, technology appraisals programme director at NICE, says the committee originally felt that “the magnitude of overall long-term benefit offered by elosulfase alfa was uncertain” but that the managed access scheme meant the drug would provide ‘acceptable value for money’.
He adds: “The drug is also very expensive at a cost of £395,000 per patient per year. We are therefore pleased that the company and NHS England have agreed a scheme that will allow patients with this condition to access elosulfase alfa while at the same time generating valuable evidence on its use through research and collection of ‘real-world’ data directly relevant to patients in the UK.”
FDA doubts
BioMarin’s group vice president and regional manager of Europe, the Middle East and Africa, Jim Lennertz, welcomed the Institute’s decision, the company faces an uphill struggle to gain approval in the US from the Food and Drugs Administration (FDA), which is considering another of its ultra-orphan drugs, Kyndrisa (drisapersen), for people with Duchenne Muscular Dystrophy (DMD) that is amenable to exon 51 skipping.
Ahead of an FDA meeting to review the clinical effectiveness and safety of the drug, BioMarin published details of the pooled analysis of three placebo-controlled studies of Kyndrisa. The studies found improvements in the six-minute walk distance test after 48 weeks of treatment.
But it appears the Administration is less convinced. A letter posted by its central nervous system drugs advisory committee was highly critical of BioMarin’s submission, saying the efficacy data from the three clinical trials “does not reach the level of substantial evidence” necessary for approval, and referred to “severe toxicity across many organ systems.”
The committee discussed the overall strengths and weaknesses of the application, but was not asked to vote on a recommendation for approval of Kyndrisa, and a negative letter does not necessarily mean a drug will be rejected by the FDA. Jean-Jacques Bienaimé, chairman and chief executive officer of BioMarin, remains upbeat, saying: “After the meeting, our next step is to continue working with the FDA as they complete their regulatory review.”
The ultra-orphan battle
The FDA has published new guidance on DMD trials that are submitted for consideration for approval. And speaking at the FT global pharma and biotech conference in London this month, David Meeker, president and chief executive of Genzyme, said his dealings with regulators had become ‘increasingly transactional’, and questioned ‘misconceptions’ around ultra-orphan drug R&D.
“I’m a huge fan of regulators and I think they have a very difficult job. But I do see here in Europe that it can become a politicised process and that’s not what we as customers would want. Reimbursement conversations have become much more transactional; even though you don’t need a p value to see the difference that these treatments can make.
“I wonder whether there’s a perception that research in orphan drugs is easier to do, because the trials are small – our pivotal trial in Gaucher’s Disease has just 12 patients. This is a misconception. We need to understand a rare disease, we need novel discussions with regulators, there is often a lack of validated endpoints, and very few patients as these diseases are extremely rare, which means we have to work with specialist centres. So they are expensive and difficult to research.”
In the case of Vimizin, the cost of treating people who may want it could amount to £30 million per year. But Meeker says even at these costs, ‘prices are sustainable’.
“There was a view a few years ago that there would be a tsunami of approvals and that it was going to break the system. But there’s been no tsunami, despite the science, the understanding of the disease and the specificity of the targets being better than it’s ever been. That will accelerate treatment, but the solution to these problems is drugs. Competition is important and it’s a good way of challenging prices in some areas. But it does not work so well for specialty drugs, where despite competition I believe prices are sustainable. We need to preserve the system.”
Jean-Paul Clozel, chief executive of specialist rare disease firm Actelion, added: “I think we should take decisions not on price but on the science. After that people have to be reasonable; but that does not mean that the value is going to decrease. There’s such a big unmet need [in rare diseases] that prices are compatible with the drugs of today. Even for orphan drugs, the price is still compatible for big companies like Novartis and Roche.”
Lilian Anekwe
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