FDA approval of Tibsovo with Dr. Amir Fathi

Leigh Clark:    Hi everyone, this is Podcast for Patients with the Aplastic Anemia Aplastic Anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… and MDS International Foundation. I'm Leigh Clark, director of patient services. Our podcast is brought to you with special thanks for our generous support of patients and families and care givers like you and our corporate sponsors. Thanks to everyone for supporting the series.
    Today we're going to be talking about the recent FDA approval of Tibsovo with Dr. Amir Fathi, who is an associate professor of medicine at Harvard Medical School and the director of the leukemia program at Massachusetts General Hospital. Welcome, Dr. Fathi.
Amir Fathi:    Thank you so much for having me.
Leigh Clark:    What is refractory refractory: Not responsive to treatment or cure. For example, refractory anemia is a low red blood cell count that doesn't respond to standard treatments. or relapsed MDS?
Amir Fathi:    Well, it's myelodysplastic syndromes myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… that has either not responded to treatment, or has initially responded, but then has returned, clinically to impact the patient.
Leigh Clark:    The FDA recently approved Tibsovo for MDS. Can you discuss the clinical trial clinical trial: A type of research study that tests how a drug, medical device, or treatment approach works in people. There are several types of clinical trials. Treatment trials test new treatment options. Diagnostic trials test new ways to diagnose a disease. Screening trials test the best way to detect a… that led to this approval?
Amir Fathi:    Well, the approval was based on results from sub-study of, patients with MDS in a pivotal, clinical trial as a phase one, looking at 18 patients. Uh, 38.9% of these patients,   with MDS, relapsed and refractory, achieved a complete remission which is remarkable. The overall objective response rate was 83.3%. And, the median time to complete remission in responding patients was approximately two months, 1.9 months, specifically.
    01:53    Also importantly, a sizable proportion of patients who were transfusion dependent prior to coming on study, became transfusionally independent and as many of the audience probably know dependence on transfusions is oftentimes a challenging aspect of treatment for MDS. It really impacts quality of life so achieving that endpoint is very good to hear.
Leigh Clark:    Who was eligible to be treated with Tibsovo?
Amir Fathi:    On the clinical trial? This was a study of relapsed and refractory MDS patients.
Leigh Clark:    Thank you.
Amir Fathi:    Who had, and this is important, obviously, they had to have IDH1 mutations because ivosidenib ivosidenib: A small molecule inhibitor of isocitrate dehydrogenase-1 (IDH1), which is mutated in several forms of cancer, including acute myeloid leukemia (AML). , the drug that was approved is an IDH1 inhibitor.
Leigh Clark:    Thank you. And how does the treatment work?
Amir Fathi:    The treatment is an oral medicine that's given once daily.
Leigh Clark:    Great. And what are the known side effects?
Amir Fathi:    Well the prominent,  side effects that have been seen in clinical trials clinical trials: Clinical research is at the heart of all medical advances, identifying new ways to prevent, detect or treat disease. If you have a bone marrow failure disease, you may want to consider taking part in a clinical trial, also called a research study. Understanding Clinical Trials Clinical… of ivosidenib are prolongation of the QT interval which is an interval on the EKG that can impact some patients. The majority of folks that are treated, however, we can clinically manage and the QT prolongation has not been a clinical challenge in those situations.
    Another adverse event that can arise with treatment of various targeted therapies including IDH inhibitors, or in this case an IDH1 inhibitor, is differentiation syndrome which, basically, is a syndrome that arises as a result of the mechanism of action of the drug which leads to differentiation and maturation of abnormal malignant MDS cells which is good. But sometimes that leads to a very robust inflammatory process caused by, cytokine mediated cascade and patients can get very sick. Patients can have fevers. They can have pleural effusion, lung infiltrates, rashes, and if the syndrome becomes very severe, it can be dangerous and lethal and generally, it is managed effectively with steroids. So I would say those are the two unique side effects that I think are important to consider with this IDH1 inhibitor.
Leigh Clark:    Once a patient starts treatment, what should they expect? How soon should they see a response to treatment?
Amir Fathi:    Well, it, it can take some time. Um, sort of the range of response was anywhere between one month and, uh, I think almost six months if I remember correctly. Um, and the median, uh, time to remission, as I mentioned earlier was, uh, 1.9 months, or approximately two months.
Leigh Clark:    What else should patients know about the treatment?
Amir Fathi:    Well, they should, if they have a diagnosis of myelodysplastic syndrome, they should ask their physicians about whether they have any mutations and, specifically an IDH1 mutation mutation: Any change or alteration in a gene. A mutation may cause disease or may be a normal variation. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a mutation in the PIG-A gene of a single stem cell in the bone marrow. because this drug has now been approved for relapsed refractory MDS with an IDH1 mutation. It is important to note that it is a relatively uncommon mutation, but if you have it, this might be an option for you.
Leigh Clark:    Well, thank you so much, Dr. Fathi for sharing your time and your expertise with all of us in discussing this new treatment for patients. If you'd like to find out more about MDS treatments, they are available on our website at aamds.org. You can also learn more about MDS and treatments on our Facebook page, Instagram, and X or you can give us a call on our helpline, 800-747-2820. Thank you for joining us.
Amir Fathi:    Thank you for having me.