Oral Therapies in the News Again

People with MS could very soon have access to oral treatments, if results of recent drugs trials are anything to go by. Oral therapies have increasingly coming to the fore for researchers in the MS field, as a number of trials near their conclusion.

The possibility that oral therapies could soon be introduced will be great news for the many people on MS who must take injections as part of their treatments.

Some oral therapies currently under investigation include:

Cladribine

Merck Serono, the makers of Cladribine, an oral therapy for MS, are seeking a European licence for the drug. The move by the company comes after detailed results of a two year study into Cladribine were released in April.

The results showed that annual short-course treatment with Cladribine tablets led to a significant reduction in the rate of clinical relapses, disability progression and brain lesions, as well as a significant increase in the proportion of patients who remained relapse-free.

“All primary and secondary endpoints of the study were statistically significant and demonstrate that annual short-course treatment with Cladribine tablets in this study was effective,” said Dr. Gavin Giovannoni, Principal Investigator of the study.

Over the two-year period of the study, 80% of the patients treated with the low-dose course  of Cladribine tablets and 79% of the patients treated with the high-dose course experienced no clinical relapse, compared with 61% of the patients from the placebo group.

Treatment with Cladribine led to a more than 30% reduction in the risk of disability progression.

In addition, there were sustained and significant reductions in different types of brain lesions for people on low and high doses of Cladribine tablets.

The most commonly reported adverse effects on those taking Cladribine were headaches, nasopharyngitis (a viral infection), upper respiratory tract infections and nausea.  Lymphopenia (a reduction of white bloodcells) occurred more frequently in the Cladribine treatment groups.

In patients treated with Cladribine tablets, four malignancies were reported during the study (cervical stage 0, melanoma, ovarian and pancreatic). Merck Serono has said that observed malignancies were isolated cases across different organ systems, but ongoing clinical studies with Cladribine tablets will provide data on a larger patient population and a longer duration of treatment to collect more conclusive information on this safety aspect.

If Merck Serono’s application meets all of the regulations set for approval by the European Medicines Agency, it could be available as early as mid-2010. 

Fampridine

Meanwhile, 'The Lancet' reported the results of a trial for experimental drug, Fampridine in February.

The phase III study, which involved 301 people with both relapsing and progressive MS, has suggested that Fampridine improves motor function in people with MS.

The participants of the trial were treated for 14 weeks, and results showed there was a consistent improvement in walking speed for more people taking Fampridine than those taking the placebo. Some 34.8% of those taking the drug saw improvement in walking speed compared with 8.3% on the placebo.

While the latest trial shows that Fampridine can be effective in improving mobility, the drug was previously studied s a possible treatment for fatigue and cognitive issues, such as memory and concentration.

Research into Fampridine has been going on for some time. In 2003, an independent review showed that 54% of participants reported improved muscle function, while 9% reported improvements in walking. However, there were no apparent effects on cognitive symptoms in that review.

Fampridine, another oral therapy, works by blocking some of the chemical processes in the nerves. It is believed it improves transmission of messages along damaged nerves.

Common side effects experienced by users of the drug have included falls, dizziness, insomnia, fatigue, backpain, nausea and balance disorders.

Fingolimod

Yet another drug that is making strides in the oral therapy research field is Fingolimod, which is being studied in both primary progressive MS and relapsing/remitting MS.

New data, released in April, showed that 80-83% of patients on oral Fingolimod (FTY720) were relapse-free for one year. These figures improve on an earlier study, which showed that Fingolimod reduced the annualised relapse rate by more than 50% in comparison to another placebo.

Results of both studies are to be released to a peer-reviewed journal in the next few months, and makers of Fingolimod, Novartis, hope to submit it for approval in the EU and the US by the end of 2009.

"Transforms is the first Phase III clinical trial to show that oral fingolimod may provide patients with an alternative choice to currently available medications for treating relapsing-remitting multiple sclerosis," said Dr Jeffrey Cohen, Lead Investigator of the Transforms study and physician at the Cleveland Clinic Mellen Center for Multiple Sclerosis Treatment and Research in the US.

Longer-term results from an ongoing phase II study showed continued low relapse rates after four years of treatment with Fingilomod.

The most commonly reported adverse effects of the drug, seen in more than 10% of the patients, have been headache, nasopharyngitis and fatigue.

Some patients have also experienced transient reductions in heart rate at the start of treatment, small increases in blood pressure on average, elevations in liver enzymes (also seen with interferon beta-1a), and a small number of cases of macular edema.

In terms of serious adverse events, infections, bradycardia (slowed heart rate) and atrioventricular block, malignancies and dyspnea (shortness of breath) were reported in less than 2% of patients.

Are oral therapies for you?

It is likely that many people with MS will favour an oral treatment over an injection as it would be less invasive, painful and more convenient. However, as with any treatment, the deciding factor will be what suits you and your MS.

While some of the oral therapies are likely to be licensed within the next three to five years, it will be some years after that their long term effectiveness will become apparent. It will also take some time for the oral therapies to find their place among the other disease-modifying therapies.

As always, we recommend speaking to your neurologist about any changes to your treatment.