JAK2 inhibitors

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JAK2 inhibitor drugs are a new type of treatment for myelofibrosis (MF) and potentially other types of MPDs as well. These drugs have not been approved for use in all people with myelofibrosis – they are still under trial.

What we’re learning

There are several different types of JAK2 inhibitors now under trial – researchers are currently studying how safe and effective these drugs will be in treating myelofibrosis. The trials are showing that many of these inhibitors reduce spleen size and other symptoms of myelofibrosis, for instance bone pain and night sweats. Investigators are now exploring whether these drugs can also extend the lives of people with myelofibrosis.

Trial phases

Drug trials are divided into three phases: I, II and III. The first phase is an initial test with a small group of patients. If the drug appears to be safe and effective, more patients can try the drug in Phase II and many more in Phase III. You can learn more about how trials work on our Trial Basics page.

As of March 2011, six different JAK2 inhibitor drugs are moving to to Phase III studies. These drugs appear to be relatively safe and that they are at least somewhat effective in treating myelofibrosis. Two additional inhibitors are in early phases of trials, and we don’t know yet whether they will prove safe and effective.

JAK2 inhibitors currently under trial

INCB018424

Who makes it? This drug was developed by the company Incyte and in partnership with Novartis

Which phase is it in? This drug has gone through Phase II of the trial and is in Phase III now.

What are the results? The Phase II results showed that 52% of people with myelofibrosis who took the drug had a reduction in symptoms related to the disease – whether or not the patients were JAK2 positive. Unfortunately, the drug does not appear to have reduced the fibrous material in the bone marrow in these patients.

What’s next? There are two large groups of patients participating in Phase III of the trial – we’ll learn more about how well the drug performed in Phase III late in 2011. A press release  concerning the initial results of one of the Phase III trials (called COMFORT I) gives more details about how the drug performed, with more results expected soon.

CEP-701

Which phase is it in? The drug CEP-701 or lestaurtinib (Cephalon) has gone through Phase II. The patients who took this drug were all JAK2 positive.

What are the results? This treatment reduced the symptoms of 27% of the people who took it, but did not reduce fibrosis or the amount of JAK2 V617F. Some patients experienced a variety of side effects, including anaemia, low platelet counts and gastrointestinal upset.

TG101348

Which phase is it in? TG101348 (Targenen/Sanofi) has gone through Phases I and II.

What are the results? The patients who took this drug tolerated it very well, although many experienced mild to moderate diarrhoea and vomiting. It decreased spleen size in 42% of the patients in the trials. Some people in this trial continued taking the drug for six months, and in those people the drug reduced the amount of mutated JAK2 in their blood.

SB1518

Which phase is it in? The drug SB1518 (S*Bio) was tested in a Phase I and II study.

What were the results? Most people who took this drug experienced very few and minor side effects. The drug reduced spleen size by half in 39% of patients. It also reduced other uncomfortable symptoms of myelofibrosis such as pain, feeling full, and night sweats by 40 to 65%. Importantly unlike the other compounds discussed to date it does not reduce platelet counts in most patients.

CYT387

Which phase is it in? CYT387 (Cytopia) has gone through Phases I and II.

What were the results? Some patients needed fewer transfusions while taking this drug. The drug reduced spleen size in nearly everyone (97%) who tried it. The drug didn’t cause many side effects.

XL019

What were the results? XL019 (Exelixis) has been evaluated in 21 patients with myelofibrosis but the studies were stopped as patients developed excess headaches and dizziness.

What’s next? Trials of XL019 have been halted in development due to neurotoxicity.

These drugs appear to be relatively safe and appear to reduce the symptoms of MF.