luspatercept-increased-hemoglobin-decreased-transfusion-requirement-in-beta-thal

Perhaps just as exciting as the gene therapy.  This drug may be useful as people await gene therapy.  Perhaps it can be used to enhance the results of gene therapy for some.  A lot of potential, I'm sure. 

So great to see all of the great results being presented!

SAN FRANCISCO – The recombinant fusion protein luspatercept increased hemoglobin levels in patients with nontransfusion-dependent beta-thalassemia, according to study results presented at the ASH Annual Meeting and Exposition.

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Luspatercept (ACE-536, Acceleron Pharma) — which contains a modified activin receptor type IIB linked to the Fc protein of human immunoglobulin 1 (IgG1) — also decreased the need for transfusion and serum ferritin levels in transfusion-dependent patients with beta-thalassemia, results showed.

“This compound has demonstrated an ability to correct anemia and improve the clinical condition of thalassemia in animal models,” Antonio G. Piga, MD, of the Azienda Ospedaliero-Universitaria San Luigi Gonzaga in Turin, Italy, said during a press briefing. “It has been tested in humans in phase 1 and now phase 2, and these results in beta-thalassemia are extremely exciting.”

The analysis included 23 patients who were nontransfusion dependent — or who had received fewer than 4 units of red blood cells 8 weeks prior to baseline — who had an 8.3-g/dL mean baseline hemoglobin level. The study also included an additional seven patients who were transfusion dependent, defined by the receipt of at least 4 units of red blood cells 8 weeks prior to baseline.

The median age of patients was 34.5 years (range, 20-57), 53% were male and 83% had previously undergone splenectomy.

All patients received subcutaneous luspatercept every 3 weeks for up to five doses in 0.2-mg/kg, 0.4-mg/kg, 0.6-mg/kg, 0.8-mg/kg or 1-mg/kg doses.

The primary endpoint was a ≥1.5 g/dL hemoglobin increase for at least 2 weeks for nontransfusion-dependent patients, and a transfusion burden reduction of ≥20% over 12 weeks for transfusion-dependent patients.

Researchers noted 75% of all patients who received 0.8-mg/kg or 1-mg/kg doses of luspatercept achieved the study’s primary endpoint.

All seven transfusion-dependent patients experienced a ˃60% reduction in their transfusion burdens.

Four of five transfusion-dependent patients with iron overload at baseline had a decrease in liver iron concentration ranging from 0.7 mg/g to 4.7 mg/g at 16 weeks. All five patients exhibited 12% to 60% reductions in serum ferritin levels from baseline.

Among nontransfusion-dependent patients, eight of 12 who had iron overload at baseline experienced ≥1 mg/g decreases in liver iron concentration by 16 weeks.

One transfusion-dependent and one nontransfusion-dependent patient each experienced the resolution of long-standing leg ulcers after 3 months of treatment, Piga said.

The most common adverse events associated with luspatercept were bone pain (20%), headache (17%), myalgia (13%) and asthenia (10%). Data showed there were no changes in platelet or white blood cells, and there were no serious adverse events.

“These are preliminary results and we are very excited to start a large phase 3 trial to [confirm them],” Piga said.

For more information:

Piga AG. Abstract #53. Presented at: ASH Annual Meeting and Exposition; Dec. 6-9, 2014; San Francisco.

Disclosure: The researchers report research funding and honoraria from; board of directors/advisory roles and employment with; and equity ownership in Acceleron Pharma, ApoPharma, Celgene and Novartis.

PERSPECTIVE

Julie Panepinto
The next step for beta-thalassemia with this agent is looking at phase 3 studies. Is there really a significant improvement in anemia as they test this in a large group of patients? These are very promising data that will allow us to move forward to the next step in research.

http://www.healio.com/hematology-oncology/hematology/news/online/%7Bf03f3ed5-6cc5-4379-b208-915b0ffbe3d3%7D/luspatercept-increased-hemoglobin-decreased-transfusion-requirement-in-beta-thalassemia

Do we know if this will be trialed in the US? If it is, patients should jump at the chance to participate. Dr Piga must be so excited about these results.

Think about this and how this was over a relatively short period of 16 weeks. That will make a huge difference in the management of thalassemia. Let's hope for even better results over time. The price of gene therapy is going to be ridiculous at first. Approaches like this will probably be a much more practical route for most patients until the price of gene therapy becomes more realistic.

All seven transfusion-dependent patients experienced a ˃60% reduction in their transfusion burdens.

Andy,

That is great.  I hope the larger studies are available to everyone soon. I would start little A tomorrow if I knew how and where!

 Also thinking of intermedias - and Manal's son right now.

I am happy to hear that iron stores are used in blood production - therefore iron overload us treated by this drug!   So much potential and seemingly few risks.  Being on such a treatment plan will surely keep
Patients healthy as they await gene therapy.

Great news...

We need to find out about Phase 3 trials for this drug. Dr Piga would not be on board unless it shows great promise, which I believe has already been demonstrated.

Andy,

Do you think this drug would be effective for beta zero patients like my son?

I will try to get more information about where and when phase 3 trials will take place. 

Yes, I do. The transfusion requirements were down for all the thal majors in the study. Even reducing it my one half would make management so much easier.

One more thing here. If Dr Antonio Piga is involved, expect it to be a success. He does not chase after false hopes, only good science. His work was instrumental in the development of combination chelation. His work has saved the lives of many patients. I think this drug has true potential.

Thanks Andy for the update!! I hope this soon becomes a success and is sold in open markets.

Thank you Andy, I look forward to this drug being readily available.

Sharmin

Sharmin,
Thank you for posting it.

Andy,
Thank you for your encouraging comments. Looks like so many different treatment options are opening up for Thalassemia. It is all good news and something to look forward to.

Bostonian and Sharmin, I don't know if you remember, but Dr Piga was at the NYC conference we attended. He told me there that his favorite part of the conferences is outside the sessions, when he can meet the patients and families. He truly loves the patients and always has their best interests at heart. I have great faith in his abilities.

Thank you Andy and others.

Hoping soon all thalassemia major will get something to cheer....

All the very Best to doctors and researcher

Has anyone contacted Acceleron or Dr. Piga to inquire when they plan to start phase III studies? They are starting phase 2 extention studies at the moment which are slated to complete in 2017  according to their clinical trials.gov page:
https://www.clinicaltrials.gov/ct2/show/NCT02268409

If anyone has any contact info. for Dr, Piga I would be grateful to have it.
Thanks!

Competition is wonderful news for Thalassemia patients. Just 10 years ago, there was very little hope for the cure. Now companies are pumping money into research to find cure for thalassemia. Nobody wants to loose the money, so they feed on competition, finding best cure at cheaper rates......

So far we know there are atleast three main streams in this respect.

BlueBird
MSKCC
Acceleron

We know there are others as well. Good Luck people, see what future holds for us in next 5 years.....I am optimistic.