Merck seeks cladribine renaissance as oral MS therapy

Merck KGaA is undaunted by earlier rejections of its oral multiple sclerosis drug cladribine and will file for approval of the drug in Europe.

Hopes that cladribine could join the ranks of oral therapies for MS seemed dead four years ago, when the US FDA said it was concerned that the drug could have a link to cancer. However, Merck pressed on with phase 3 trials of the drug which have now reinforced its view that the drug is safe.

"The decision follows the company's evaluation of new data and additional analyses of the compound's benefit-risk profile," said Merck in a statement.

The new information comes from studies already in progress when the programme was halted in 2011, and it is understood that no new trials have been carried out. Additional safety data has also come from a registry study.

Merck has submitted a letter of intent to the European Medicines Agency (EMA) detailing the new analysis, kicking off a process that could lead to a fresh marketing application. The company said it also plans to pursue approvals in other world markets.

Assuming Merck can gain approval for cladribine in MS, a big question is whether it will reach the market too late to make any meaningful impact. Since it was rejected in 2011, three oral MS drugs have reached the market - Novartis' Gilenya (fingolimod), Biogen's Tecfidera (dimethyl fumarate) and Sanofi's Aubagio (teriflunomide).

Among these, Tecfidera racked up sales of $2.9 billion last year, just ahead of Gilenya which added $2.5 billion to Novartis' coffers despite the Swiss firm's relative inexperience in the MS sector. Sanofi's Aubagio was a distant third, but still managed to approach $500 million in sales last year.

Earlier hopes that cladribine could become a $1.5 billion product in MS seem unlikely to be realised. That said, approval with no new trials required could mean relatively modest sales would still give the German drugmaker a welcome return on its investment in the programme.

"While the options available to treating neurologists have grown over the years, cladribine tablets have the potential to offer a truly innovative addition to the armamentarium physicians have at their disposal to treat their patients," said Professor Giancarlo Comi, director of the Institute of Experimental Neurology (INSPE) in Italy who was an lead investigator in trials of the drug.

Cladribine is a chemotherapeutic drug used for the treatment of hairy-cell leukaemia. Short courses of the drug have been shown to induce prolonged reductions in white blood cells and - because of this immunosuppressive effect - it has been studied as a treatment for MS which is thought to result from an autoimmune reaction to the myelin sheath surrounding neurons.

The oral therapies are steadily being used in favour of older, injectable drugs including beta interferons such as Biogen's Avonex, Bayer's Betaferon/Betaseron and Merck's own Rebif brand, as well as Teva's big-selling Copaxone (glatiramer acetate) product.

Such is the impact of the new oral therapies that only one injectable - Biogen's long-acting Avonex follow-up Plegridy - is showing positive growth, according to a recent analysis by Spherix Global Insights.