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Acceleron "Luspatercept" drug increases RBC count blocking a type of protein

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sofear:

--- Quote from: catchR on May 05, 2015, 09:55:02 AM ---Fresh update on Luspatercept:
http://www.bizjournals.com/boston/blog/bioflash/2015/05/acceleron-gains-and-bluebird-falls-in-blood.html


More on latest study from Acceleron - Luspatervept: http://investor.acceleronpharma.com/releasedetail.cfm?ReleaseID=910306

--- End quote ---


--- Quote ---In the higher dose groups (0.75 to 1.75 mg/kg administered subcutaneously every three weeks):

* 54% achieved the International Working Group (IWG) hematologic improvement-erythroid (HI-E) threshold of efficacy.
* 36% of patients who received red blood cell transfusions during the 8 weeks prior to treatment in the study achieved transfusion independence for at least 8 weeks during the study.
Ring sideroblasts (RS) are a type of abnormal red blood cell (RBC) precursor cell in the bone marrow. These ring sideroblasts are associated with ineffective erythropoiesis and anemia. When at least 15% of the cells in an MDS patient's bone marrow are ring sideroblasts, this patient is considered RS positive. At least 30% of all MDS patients are RS positive, and the proportion is likely even greater within the lower risk segment of all MDS patients.

In the RS positive patients in the higher dose groups treated with luspatercept,

* 63% achieved IWG HI-E
* 39% achieved transfusion independence
--- End quote ---

Just in case someone wants to know what exactly that means. I had to search for it, too:


Source: http://www.bloodjournal.org/content/bloodjournal/108/2/419.full.pdf

I'm currently a bit confused what the difference between Sotatercept and Luspatercept is. I haven't been following the studies in detail. The website of Acceleron states:


--- Quote ---Sotatercept and luspatercept are biochemically distinct molecules and may have unique pharmacological attributes that enable their preferential use in particular anemia indications.  Notably, unlike sotatercept, luspatercept does not bind with high affinity to activin A.  In preclinical studies, luspatercept promoted red blood cell (RBC) formation in the absence of erythropoietin (EPO) signaling, had distinct effects from EPO on RBC differentiation, and acted on a different population of progenitor blood cells than EPO during RBC development.  In these studies, luspatercept did not promote significant increases in bone mass.
--- End quote ---
Source: http://www.acceleronpharma.com/products/luspatercept/

I found a topic on the forums with that exact question, but it has not been answered, yet: Luspatercept vs. Sotatercept

I found some old data on Sotatercept in a presentation. It's interesting how dosage and change in Hemoglobin correlate with each other:


Full presentation: http://www.cooleysanemia.org/PowerPoint/A536-04.pptx

The presentation also mentions the following:


--- Quote ---Further dose escalation is ongoing; longer-term extension studies are planned
--- End quote ---

The Luspatercerpt doses seem to be in the same area as the the Sotatercept ones, but the recent results seem to include 'higher dose' groups, which receive 0.75 to 1.75 mg/kg every three weeks, while the Sotatercept presentation only mentions maximum doses of 0.8 mg/kg.

I found another study where Sotatercept doses of up to 1.5 mg/kg are mentioned: Study to Determine the Safety and Tolerability of Sotatercept (ACE-011) in Adults With Beta( β)- Thalassemia

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