Mass. General Cancer Center Hematologist, Dr. Hanny Al-Samkari talks about a new therapy that lessens symptoms of PKD.
Interview conducted by Ivanhoe Broadcast News in 2022.
What is PK deficiency?
AL-SAMKARI: PK deficiency or pyruvate kinase deficiency, is a congenital blood disorder characterized by anemia. Anemia being too few red blood cells, red blood cells being the type of blood cells that carry oxygen from your lungs, to the rest of your body, your muscles, organs, your brain to give you energy. And in PK deficiency, people become anemic because their red cells run out of energy quite literally. Red cells need energy just like any other cell in the body, and they are dependent on this enzyme called pyruvate kinase to ensure they have adequate energy. Other cells and body aren’t dependent on this enzyme, but red cells are. And so when there’s not enough of this enzyme, there’s not enough energy and the red blood cells break up in the bloodstream, that’s called hemolysis or breakdown of the blood cells. Patients with PK deficiency therefore have lifelong hemolysis and anemia- hemolytic anemia. And that results in a reduced quality of life, reduced energy, or reduced exercise tolerance, and ability to work a full day of work or school for many patients. A dependence on blood transfusions for many patients in order to have a high enough blood count to be able to live a pseudo normal life or even to survive. And the breakdown of blood itself, the hemolysis part actually causes a whole host of other organ problems, like liver disease and heart disease, can cause brittle bones and bone fractures can cause blood clots. So this is a really significant disorder and people who have it, they’re born with it. They have it for their whole entire lives.
Can it be fatal?
AL-SAMKARI: PK deficiency in causing liver disease and heart disease actually can be fatal. The iron overload that these patients have from the red blood cells breaking up in the bloodstream actually can lead to liver failure, liver cancer, and heart failure and sudden cardiac death.
You had mentioned patients have this since birth, is this a genetic condition or do you know what causes it?
AL-SAMKARI: Yes. PK deficiency is genetic. People are born with it. It’s from two abnormal genes that encode for the pyruvate kinase enzyme. And so very commonly, a person is born with this disease and neither of their parents had it. It’s not something that they’ve ever recognized in their family because both parents were just carriers and there’s no consequence to being a carrier.
What are the treatments been till now, you mentioned that some patients needed a lot of transfusions. Have there been any medical therapy that was available to patients?
AL-SAMKARI: Treatments for pyruvate kinase deficiency before the development of this new drug were really limited to blood transfusions and folic acids supports to help the body make as many blood cells as possible. And supportive treatments, basically, therapies for all of the complications of the disease. Nothing that targeted the specific problem in the disease, and certainly nothing that could cure it.
Can you talk about this new treatment, this new medication and how it works and how it works with patients?
AL-SAMKARI: This new treatment is a medicine called mitapivat. And mitapivat is a drug, a pill that you take twice a day that really revs up the pyruvate kinase enzyme. It attaches to the enzyme and it causes the enzyme to work more efficiently, changes the shape of the enzyme in such a way that the enzyme is able to do its job better. And this doesn’t work for every patient who has pyruvate kinase deficiency because there are many different genetic mutations that lead to pyruvate kinase deficiency. But for a large percentage of patients with pyruvate kinase deficiency, this enzyme really improves the energy levels in their red blood cells. And that stops the red blood cell breakdown and thereby, resolves the anemia, as well as the complications of the red cell breakdown that cause so much suffering and so many of these problems. So we have patients receiving mitapivat that have had a dramatic improvement in their blood counts or even normalization of the blood counts. Well, on this medicine that you couldn’t even tell that they had pyruvate kinase deficiency if you looked at their blood tests and their laboratory tests. So really remarkable improvements and many patients on it feel so much better, have a new lease on life and are very happy to not have to worry about all of the longer-term, potentially not have to worry about all the longer-term complications of the disease.
Is this a game changer in terms of patients and doctors and treatment of the disease?
AL-SAMKARI: Yes. Mitapivat really is a game changer. It’s the first disease modifying therapy in pyruvate kinase deficiency, the first drug ever FDA approved to treat pyruvate kinase deficiency. And so it’s a really major breakthrough for these patients.
Can you talk about your patient Bill?
AL-SAMKARI: Yeah. So Bill, I have known Bill for many years now. Bill first when I first met Bill, he had rather substantial anemia. He told me a story about how his disease had not been picked up until later adulthood despite the severity of the disease because everybody just assumed that it was something else, didn’t recognize it was this rare hemolytic anemia, rare genetic disease. He was trying to work full time and not able to do it. He just did not have the energy to get through a day and I couldn’t blame him even for a second, with those blood counts, I couldn’t get through a day. And the disease have really had a major impact on his quality of life in lots of different ways and also on his health in other ways just from the problems of this chronic blood cell breakdown. He got treatment with mitapivat and his life has completely changed for the better. I’m just so happy. This is why you choose to become a doctor, this is why you choose to do research in rare diseases. He enrolled on this clinical trial and his improvements were very clear on mitapivat and he now remains on the drug. I’ve never seen his blood counts looks so good. And he now has all the energy to do everything he wants to do and his quality of life has just gotten so much better. And I am also expecting that over the long term because his disease is much less severe on this drug that he is hopefully being protected against a lot of these longer-term complications of the disease.
You mentioned that his blood counts were so low that you wouldn’t have even been able to function? Do you remember how low he really was? And just for our viewers, can you put that in context what is a normal blood count?
AL-SAMKARI: He had been living with a hemoglobin of seven or eight grams per deciliter, which is, that’s the bare minimum that we think about in terms of if you get below that for many diseases, people put you on regular blood transfusions and Bill had gotten intermittent blood transfusions but didn’t really want to be on regular blood transfusions. And normal hemoglobin in an adult male is 14, 14 really tests, 17 or 18. So having a hemoglobin of eight is about half of really what it should be. And so that reduction in the oxygen carrying capacity of the blood has real impact on your ability not only to work a whole day at work, but even the climb two or three flights of stairs, you just get tired. Everything is a major push. You feel like you’re dragging all the time. And that was those were Bill’s initial complaints. And I completely understand why he had them and with mitapivat his hemoglobin has improved several grams, he’s doing very well with really no further symptoms or manifestations of anemia.
Can he be on this medication for the rest of his life? And do you anticipate that he would be or is there, I know it’s newly approved. Do we know what the implications could be down the road?
AL-SAMKARI: Yeah, that’s a great question. I mean, we obviously are expecting, based on the way the medicine works and the fact this is a genetic disease, that when somebody responds, that they should keep that response. And that’s really what we’ve seen just in general. And I think if you asked Bill if he ever wants to come off the medicine, he’d probably would give you a very clear answer of no. But for our patients that have responded nicely, we expect that, I never say forever or for the rest of one’s life, I’d like to say indefinite because I don’t know what we might have, it’s possible we may have more therapies in the future. There’s gene therapy being developed in pyruvate kinase deficiency that’s very early. But we have realized gene therapy and other related diseases. And so that’s a potential option for some of our patients, not without its own potential risks, but for the indefinite time course, I expect that he’ll be on it, yes.
Is there anything I didn’t ask you about PKD or about Bill that you would want people to know?
AL-SAMKARI: I would just say this is a great example of the benefits and the synergy between academic clinician researcher like myself, as well as industry companies that take an interest in these rare diseases. Because there are a lot of rare diseases out there and we have a lot of work to do in the field of rare disease to provide targeted treatments, and with advances in sciences for many cases, it is possible now to develop these therapies. So I look at this as a success story, but also a rubric for success in the future.
Is it covered by insurance? Does it come out of pocket for paying?
AL-SAMKARI: Yeah. So the medication is FDA approved. So ultimately Medicare covers medications that are FDA approved and private insurers tend to follow. Whenever a medicine first comes out, it’s sometimes not on formularies wherever you have to wait a few months. We’re getting over that point, and I’ve pretty much been able to get the medication for patients who wanted and need it. So yes, I mean, it is cover- it is generally covered. I can’t say that it’s covered for every insurance plan in the world, but by and large, yes. Because it’s FDA approved, it is private insurers, Medicare, or Medicaid typically cover it.
END OF INTERVIEW
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