At ASH we presented the ROP-ET study that was a study that tested a new form of interferon alpha, the ropeginterferon alfa-2b, for patients with essential thrombocythemia in need of cytoreductive therapy but who were intolerant, resistant or ineligible to all approved therapies, meaning a kind of last line trial. The primary endpoint was a composite endpoint combining haematological response with normal platelets, normal leucocytes, but also absence of thrombotic or haemorrhagic event, absence of disease progression and improvement in symptom burden of the patient. This was measured after 12 months of treatment and compared to a historical rate of 40% in this population of patients resistant to all available therapies.

A total of 132 patients could be enrolled in the trial and they were analysed for this primary endpoint, efficacy endpoint. The distribution of driver mutations was what we expect – 60% JAK2 mutant, 27% CALR mutation and a few patients triple negative.

Altogether at twelve months 48% of the patients showed a durable clinical response, the primary endpoint, so the study met its primary endpoint. If we look at the different components of this composite endpoint, 65% of the patients achieved a durable complete blood count remission. None of them showed disease progression, only two patients had a major thrombotic event and the durable improvement in their symptoms also was observed in about 84% of the patients.

So, altogether, the tolerance was also very good. It’s to note that ropeginterferon alfa-2b was started at a relatively low dose of 125μg every two weeks and then could be increased to 250μg after three months and to 500μg every two weeks after six months in case of no response. But, notably, 36% of the patients didn’t require any dose escalation and with this relatively low dose there were very few adverse events and only one patient experienced a treatment-related serious adverse event.

So, altogether this study shows that ropeginterferon alfa-2b is a favourable therapeutic option also for patients with ET who require cytoreduction but cannot receive other available therapies.

What is the clinical significance of these results?

We have now long experience of ropeginterferon alfa-2b in PV patients and it’s important to put these results in line with another study, so a past ET study that was performed in the US and in Asia that was a second-line treatment with ropeginterferon alfa-2b, providing a new therapeutic option for patients with essential thrombocythemia. We have already a couple of drugs useful in these patients but classical drugs such as hydroxyurea or anagrelide that are approved as first or second line in this disease have their limitations and many side effects such as skin toxicity, for example, for hydroxyurea, cardiac toxicity for anagrelide. So we need additional therapies to be approved in this population of patients.