All about Ivosidenib

What is ivocidanib? Ivositanib is a medication called an Idh1 inhibitor and this is an example ofology of targeted therapy. So not every patient is eligible respond to ivocidanib and only patients who have a mutation in a gene called Idh1 are eligible and would respond to ivosinib. What is an Idh1 mutation? Idh1 is a mutation that is found in about 5 to 10% of patients who have acute milo leukemia. It causes a problem in some of the metabolism of different blood cells that creates this product called 2G which makes it so that cells can grow out of control and lead to leukemia. Idh1 is found not in every patient but when it is found it is an indication that this is a patient who may be benefiting from treatment with an Idh1 inhibitor. How would a patient know if they have this mutation? A patient would know that they have an IDH1 mutation based on different mutational tests that we do. And this is frequently done at diagnosis at the time of a bone marrow biopsy where we send a test called next generation sequencing to understand what sort of gene mutations their leukemia harbors. There's other ways to detect these mutations throughout the course of someone's disease, but it is usually done from either a blood test or a bone marrow test. When during the course of treatment, would someone with an IDH1 mutation receive ivocidanib?

So ivocidanib can be given both in the first part of treatment called induction or if leukemia relapses and IDH1 can be given in both of these settings and has shown to be beneficial and have activity and can treat both initially newly diagnosed leukemia or AML that is relapsed after previous treatments. How is ivocid administered? Ivositanib is a pill that is taken every day and it is a pill that is uh taken just with with water and can be very well tolerated but it is often combined with other medications uh to improve the effectiveness of ibisetin. What is it usually used in combination with? So I sitaninib is effective by itself just given by itself either in newly diagnosed patients or in patients who have relapsed but we've also learned that ivocidanib is even more effective if given with other medications and mostly these are medications called hypomethylating agents specifically a medication called aocyitine which is an injection or infusion that's given and the combination of both of those drugs really makes it So that ivocetin works better when given with this medication. What are the common side effects of ivocitanib? How are they managed? So the common side effects of ibocitanib really it's actually very well tolerated. Now the main side effect that we really worry about with ivocetinib is a special toxicity called differentiation syndrome and it has to do with how ivocidanib works to treat leukemia by making these very early type leukemia cells grow up quickly into mature blood cells. And in that process it can cause things like fever, fluid accumulation and problems breathing. And so we monitor patients very closely for this differentiation syndrome. And if it does occur, we promptly institute medications called steroids to help treat that disease. But it is a general a pretty well tolerated medication and is not associated with a lot of lowering of blood counts that we see with other leukemia directed treatments. Can Ianib cure AML? Ivositanib is a great medication that can produce responses in patients who have Idh1 mutated AML. But unfortunately, it's not a cure for AML. And that even if you treat someone and they do get a response with Ivositanib either alone or with combination with another medication, the leukemia can come back over time. So unfortunately, it's not a cure. How effective is Ivocitanib for Idh1 positive patients? Ivositanib is very effective for the treatment of Idh1 mutated acute milude leukemia. And we measure effectiveness in a a few different ways. And one way is a response. Does the leukemia go away when we look under it under microscope that occurs in approximately 40% of patients who are treated with just ivocidanib alone. And if you add ivocidenib with combination with aocyitine that number goes up even more to 50 60% of patients. But the other way that we really measure how effective a medication like ivocetanib is is how much it really improves someone's lifespan their survival. And the combination of aocytoine and ivocetanib significantly improves a lot of these things and these outcomes versus just aocyadine alone. Importantly too, ivocetanib can also help clear that mutation, that Idh1 mutation. It can make that Idh1 mutation go away in patients who respond, especially about 20 30% of patients with a single agent and even more when given a combination with aocitine. so good at targeting that mutation, that mutation, and specifically targeting that part of leukemia that has that mutation. It's so good at making those cells not be leukemic anymore that it makes that mutation go away. What research is being done to make ivocidanib even more effective? Research in ivocitanib is taking place in a number of different ways. One way we've touched upon is how to make ivocet even more effective in Idh1 mutated patients and that includes combining it with drugs like we mentioned aocyitine before but also other medications such as venetic llax and trying to see if instead of two drugs three drugs is even better in terms of producing responses and improving survival. Other ways we're trying to improve is ivosidanib and the treatment of Idh1 mutated AML is trying to understand which patients will respond and which patients won't respond. So we can predict if you give someone with Idh1 mutated AML ivocitanib is this someone who's going to have a good outcome with it or is this someone who's not going to respond. And the last way we're really looking at to improve ivocidanib treatment is to understand how patients become resistant to ivocitanib. How do patients relapse? What are the mechanisms and what are the ways that the leukemia cells can figure out a way around ivosidib and continue growing? And identifying those mechanisms is really important so that we can develop strategies to target those mechanisms so patients can enjoy longer responses and have a longer life while being treated with ivocet. How else is ivocidanip being used? I think a really important key about ivositanib is that it has become approved now in the context of other leukemia drugs being approved namely venettoaclax. So oftent times an oncologist will have the decision in someone who's Idh1 mutated whether to treat them with aocyadine venettolax or aocitine and ivocidanib and that's a a distinction and a decision that is very hard to make because they're both very effective regimens and there is some people who want to give aid and ivocet because it is better tolerated and easier to take than aocited and venetic while other people are of the mindset that it's better to save ivocidanib later on in the disease course so you can treat someone who maybe relapsed after after aid and venettolax and so I think it's important for patients to really discuss the distinctions between those two and to make the best decision for them whether it means going for something that may be potentially better tolerated versus something that is uh potentially worse tolerated but then saving treatment options for later on in the disease course. What factors go into a patient's decision-m when choosing a treatment? A lot of the decisions have to do with risk category and about how aggressive their leukemia is. Idh1 mutations often coexist with other mutations which can influence how high risk and adverse risk someone's leukemia is. But a large percentage of the discussions have to go down have to deal with uh safety and tolerability and does the uh side effect profile of ivocet or vineetylax is is that better for that patient. So for instance venettolax can cause low blood counts often requiring transfusions and that can be very burdensome for some patients while in other patients that might not be as big of an issue. um ivocidanib and aocyitine has this risk of differentiation syndrome and some patients are really nervous about that. So it's important to have a a dialogue with your with your oncologist about these different side effects and also about the the comparing the efficacy and the treatment effectiveness of the two agents to see which one is a better choice for every individual patient.