Thalassemia and Sezuires / Epilepsy

Keep your eye on the development of this drug. It's already being used in Russia according to one of our members, where it's called Jakafi. They're had great success in reducing spleen size. Dr Ali Taher is involved with the trials, leading me to believe it must have real merit.  http://www.healio.com/hematology-oncology/hematology/news/online/%7B97bca27d-1532-4e8c-af6b-aa464abd37d5%7D/ruxolitinib-may-provide-alternative-treatment-for-patients-with-transfusion-dependent-thalassemia

Ruxolitinib may provide alternative treatment for patients with transfusion-dependent thalassemia

March 17, 2017
SAN DIEGO — Ruxolitinib demonstrated an improvement in transfused red blood cell volume during a 24-week treatment period compared with baseline in patients with transfusion-dependent thalassemia and splenomegaly, according to phase 2a results from the TRUTH study presented at the ASH Annual Meeting and Exposition.

Ruxolitinib also demonstrated a reduction of spleen volume in almost all study participants, according to the findings.

Ali Taher

Splenomegaly tends to worsen anemia in patients with transfusion-dependent thalassemia, which can then lead to an increase in the need for transfusions.

“The consistent reduction in spleen size from baseline over time observed in the study patients echoes similar results reported in phase 3 trials recruiting patients with myelofibrosis and polycythemia vera,” Ali Taher, MD, deputy director for academic and research affairs at the Naef K. Basile Cancer Institute at the American University of Beirut Medical Center, told HemOnc Today.

Taher and colleagues conducted a single-arm, multicenter study of 30 adults (median age, 24 years) with thalassemia and splenomegaly who received transfusions every 4 weeks.

The primary endpoint, as Taher noted, was to determine if there was a reduction in transfusion burden with the use of ruxolitinib (Jakafi, Incyte) compared with baseline – which was defined as the period between 24 weeks before the start of treatment and week 0.

The researchers also sought to determine if there was any degree of spleen volume reduction from baseline.

Patients received a starting dose of 10 mg twice-daily and were required to receive iron chelation for at least 4 weeks prior to screening and throughout the study.

Twenty-six patients completed the core phase at week 30 and 20 of those patients continued to receive ruxolitinib beyond the core study period via other mechanisms.

Mean hematocrit adjusted volume of transfused red blood cells per 4 weeks was 605 mL during the baseline period. The adjusted volume of transfused red blood cells decreased to 560 mL between weeks 6 and 30 after treatment with ruxolitinib. Mean percent change of transfusion rate was –5.9%.

The most common adverse events that occurred during the study were upper respiratory tract infection (27%), nausea (20%), upper abdominal pain (17%), anemia (17%), diarrhea (17%) and weight gain (17%).

Eleven patients reported experiencing grade 3 or 4 adverse events that were not believed to be associated with the use of ruxolitinib.

Thirteen patients experienced adverse events that were believed to be associated with the study drug. Three of those patients reported serious adverse events.

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In my case Sezuires / Epilepsy caused by low hb. I'm taking treatment since 2008 for Sezuires / Epilepsy. Right now I'm taking Phenobarbitone 60 mg in day and 120 mg in night, Clobazam 10 mg in night, Flunarizine 10 mg in night and Levetiracetam 750 mg twice a day . My Neurologist told me that if i stop my medicine it can happen again. So do as your Neurologist say.

Hi Andy,

Yes my haematologist mentioned something about that drug!!

....but I think he said it can only be used on transfusion dependent patients? 

Is this the case or can we independent patients try it?

Thanks a million Andy!

I would say that will depend on the doctor. Some minors have spleens large enough to have splenectomy considered, including you, so I cannot see why it should be treated any differently. It does create a vicious cycle that everyone would be better off not having. The more the spleen destroys red blood cells, the more overactive the bone marrow becomes. I think some doctors will see this drug as a better option than splenectomy for minors.

Hello Andy,

I saw my haematologist again last week and raised JakaIf with hi again and he reiterated that it's only to be used in transfusion dependant thalassemics. As I have intermedia and do not have transfusions it won't really work. My haemoglobin runs between 7-8 but recently it's dropped and were investigating why. It could be that it was the allopurinol I was taking for gout suppressing the bone marrow as its metabolised in the kidney were EPO is created to stimulate blood production. We will get a clearer picture towards mid-July if things improve as I've been off allopurinol for about 2 weeks and I believe it could take weeks for haemoglobin to recover if it does?

He did mention a new drug in phase 3 trials for non transfusion dependant thalassemics but I can't remember the specifics. I think it's available somewhere on the UK thalasemmia society website in one of their publications.

Do you have any information about these new drugs?

Thanks mate.

The drug is Luspatercept and the phase 3 trials are now full and underway. Phase 2 trials had very good results. Patients saw good increases in Hb, lower iron loads and reduced in effective erythropoiesis. This would be of great benefit to non-transfusing patients, as well as transfusion dependent patients.

The drug is Luspatercept and the phase 3 trials are now full and underway. Phase 2 trials had very good results. Patients saw good increases in Hb, lower iron loads and reduced in effective erythropoiesis. This would be of great benefit to non-transfusing patients, as well as transfusion dependent patients.

Thanks for that mate.

Do you know when these trials finish? 
P.s. How is the drug administered?

It's administered via subcutaneous injection, afaik. Someone wrote it might be on the market in the next 2-3 years (?), IIRC.

Luspatercept is administered by IV. Phase 3 trials are now full and the trials are underway in several countries. I think we should have full results within two years. It will not take long for approval once the trials are complete, as long as no unforeseen problems arise. None have during phase 1 & 2.

I'm not sure if it can be administered by IV, but in the study I think they administered it via subcutaneous injection, which, in my opinion, is the least painful or difficult administration with a syringe. I guess it could be injected into the belly fat, for example.

Yeah, that is right. It was done through subq injections, like with desferal.

Ah ok.  Just the one injection or is it a course of injections?

p.s. Spleen measured again last week and is around 23cm.

It's ongoing, so the injections would have to be done regularly.