Thomas Leist, MD, PhD: Cladribine tablets have recently been approved in the United States for the treatment of relapsing-remitting disease, as well as active secondary progressive disease. In the United States, cladribine tablets are not indicated for patients with clinically isolated syndrome, but behind the data that are currently part of the approval in the United States, there is an additional trial and this trial was carried out in patients after the first demyelinating event.
This is the ORACLE-MS trial and the study that we present is a subgroup analysis of individuals to see whether or not we can identify age groups, activity groups, as well as disease severity groups that may or may not respond to the treatment. In the study that we will present, the subgroup analysis of the patients from the ORACLE-MS trial, we can show that both younger and older patients with the first demyelinating event profited from the intervention; the results were significant compared to the placebo cohort.
We also see that patients with more or less lesions at the initial presentation and with gadolinium or no gadolinium-enhancing lesion profit [from the treatment]. We also could demonstrate that patients with a poly-symptomatic first event—so more than just optic neuritis or transverse myelitis—also profited and patients with a simple onset, just one symptom complex, profited in this.
With that, this study that is now presented as a subgroup analysis, shows us that a wide range of patients may profit; again, this is currently outside of the indication within the United States. The interesting thing in the future will be whether these patients from the ORACLE-MS trial can be reconvened and one can actually evaluate whether intervention with an agent such as cladribine tablets may potentially have a benefit way beyond the initial treatment cycle. I hesitate to use the word, but still, whether this is an induction treatment or a conditioning treatment, whether an upfront treatment may potentially affect the disease course over a very, very long period of time.
Cladribine tablets has an interesting development in that the clinical trials were actually performed some time ago and patients were subsequently off treatment followed in the PREMIERE Registry, and so we have almost 10 years of follow-up in some patients. There is a lot of information of upfront treatment and then follow-up in these particular patients—so yes there is data. There is less data on the retreated patients and so that something that perhaps over the period of time will need to be remedied; it's probably something that is not going to be done in the United States early on because approval in other countries was earlier and so maybe they have data from other areas.