Orphan Designation Is Critical to Drive Discovery in Rare Diseases

Merkel cell carcinoma (MCC) is a rare and aggressive type of skin cancer, which is both debilitating and life-threatening because of its rapid growth and ability to spread rapidly to other parts of the body. Once this occurs, the outlook for long-term survival is decidedly poor.

Unfortunately, the incidence of this deadly cancer is on the increase: in fact, it has more than tripled over the past 20 years. This is due, in part, to demographic developments – and specifically the ageing population – as MCC usually affects the elderly.

Hope is, though, on the horizon. Discovered by Merck and now being developed as part of a strategic collaboration with Pfizer, avelumab is a ‘monoclonal antibody’, a type of protein designed to recognise and attach to a protein called ‘programmed death ligand-1’ (PD-L1). This protein is expressed in many cancer cells and is thought to help suppress the body’s defences – immune cells – thereby protecting cancer cells from being attacked by them.

In targeting and attaching to the PD-L1 protein, avelumab aims to remove this suppressive effect, allowing the immune cells to recognise and kill the cancer cells. In addition, by attaching to the cancer cells, the antibody should help to kill them directly, thereby impeding the cancer’s growth.

Results from the first pivotal, international, multicentre, open-label, Phase II study of avelumab, showed that 28 of 88 patients responded to the treatment – an objective response rate of 31.8%. On top of a manageable safety profile in patients with metastatic MCC who were treated with avelumab in the second or subsequent lines of therapy, tumour responses were rapid and durable and no unexpected safety signals were reported.

This data is encouraging, but it is vital not to lose sight of the path that led to this. Drug development requires not only substantial technical knowledge but also considerable up-front investment.

A significant concern has been the limited numbers of patients with MCC, not least because it was difficult to attract a sufficient number of patients to allow the clinical trial to demonstrate safety and efficacy. Secondly, the relatively small market for MCC could potentially prevent the recovery of the investment made into the product development of avelumab in this indication.

Against this backdrop, that the right incentives and rewards exist for the innovation on offer is critical. On 14 December 2015, the European Commission granted orphan designation (OD) to avelumab for the treatment of MCC – this was key to its development.

For a medicine to be granted an OD in the EU, it must be intended for the treatment, prevention or diagnosis of a life-threatening or chronically debilitating disease, the prevalence of which in the EU must not be more than 5 in 10,000. Alternatively, it must be unlikely that marketing of the medicine would generate sufficient returns to justify the investment needed for its development, and where no satisfactory treatment is already available. If avelumab ultimately becomes an approved medicine, it will be entitled to a 10-year period of market exclusivity for this specific orphan designated condition.

If no incentive like OD had been obtainable, or such incentives were downgraded, the risk that pharmaceutical companies might not be able to invest the significant resources it takes to develop a promising compound into a medicine available to patients would be very real. As a result, investments into research and development of the specific diseases could be reduced significantly, if not abandoned altogether. This could limit the discovery of new innovative medicines for patients suffering from rare diseases, such as MCC.