Are their any open clinical trials for deletion 22-41?

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Sorry, just saw your answer about the 2nd cohort completed.
I don't know why I feel that this drug will be the first treatment in DMD
Ofelia, I'm told that the 3rd cohort never started.
That's what I thought...I know that the 2nd cohort completed but then everyone got quiet. Thanks!

Jason Gautier said:
Ofelia, I'm told that the 3rd cohort never started.

One thing I forgot to add, ACE-031 is hoped to increase muscle mass, I am not sure that the increase after 3 months is high enough to see any functional improvement. I recall that they did not see any improvement in menopausal women either although data did show increase in muscle mass... nor did they expect to see improvement after such short duration. However, the nose bleeds at such a low dose are very concerning...also the fact that they decreased the level from 2 mg to 1.5 mg.

http://www.acceleronpharma.com/content/products/ace-031.jsp

 


Multiple Ascending Dose Phase 1 Study - A study in healthy postmenopausal women (A031-02), evaluating multiple doses of ACE-031, is currently ongoing. For more information on the study design, click here. Acceleron has presented preliminary results from this study. Click here for the poster presentation of these results andclick here for the accompanying press release. As this study is not complete, final results are not yet available.


A031-02 randomized 60 subjects in 6 cohorts of 10 subjects each to receive ACE-031 or placebo (8:2) at dose levels ranging from 0.1 to 3 mg/kg given by SC injection every two or four weeks for a total of three or two doses, respectively, over a four week period. Subjects were followed for 12 weeks after their last dose. Although this safety study was not powered to assess statistically significant changes in endpoints, multiple exploratory statistical analyses were performed on the data. 


Consistent with the findings of the single dose study (A031-01), multiple doses of ACE-031 given to healthy postmenopausal women were generally well tolerated and resulted in rapid and sustained effects on muscle, bone and fat. The most common adverse events were injection site reactions, headache and nosebleeds. The majority of adverse events were mild and transient. ACE-031 had a half-life of approximately 12 days, supportive of dosing every 2-4 weeks.

Mean total body lean mass measured by DXA at day 36 increased by 5.2% from baseline in the group receiving ACE-031 at 1 mg/kg every 2 weeks. This was statistically significant compared to the 0.4% increase in the placebo group (p=0.008) and was sustained through day 57. Significant increases were also seen at doses of 2 and 3 mg/kg every 4 weeks.

Mean thigh muscle volume measured by MRI at day 36 increased by 4.1% from baseline in the group receiving ACE-031 at 1 mg/kg every 2 weeks compared to 1.1% in the placebo group (p=0.012). Significant increases were also seen at 2 mg/kg given every 4 weeks. No statistically significant changes were observed in grip strength or functional tests in this healthy volunteer safety study.





Jason Gautier said:

We are not privy to any of the results except our own, so I have no idea how other boys responded.   I just know that we didn't really see any functional improvement.   His strength and function testing seemed to remain consistent. 

He was only on it for the initial three months so who knows if we will better results longer term. 

 

I am afraid that ACE 031 can increase muscles but non functional.

Can anybody tell me why they didn't do strength assessment in healthy volunteers or even Exon Skipping?

I see that they are talking about the amount of dystrophin in Exon Skipping but they didn't mention if this dystophin functional or not!

ACE 031 recruits stem cells from blood.Maybe this is the reason of nosebleed

It's interesting you bring that up - I have another concern about dystrophin as well.  We know about the potential for immune response (http://www.nature.com/gt/journal/v7/n17/full/3301259a.html) - and yet I don't hear very much talk about it.   Are we setting ourselves up for a huge disappointment - plowing blindly forward when we don't even know if our boys' bodies will accept dystrophin?  I am curious why all of the companies that are doing exon skipping trials also aren't vigorously researching how to suppress the potential immune response.

Moein said:

I am afraid that ACE 031 can increase muscles but non functional.

Can anybody tell me why they didn't do strength assessment in healthy volunteers or even Exon Skipping?

I see that they are talking about the amount of dystrophin in Exon Skipping but they didn't mention if this dystophin functional or not!

Both AVI and Prosensa/GSK tested for immune response and did not see any to date. They are asked about it almost every presentation and they always respond that their tests did not detect any immune respone while dystrophin was expressed in all boys. We'll know more during the dosing trial planned in Columbus, as we know Dr. Mendell is very aware about the possibility. 

Steve Dreher said:
It's interesting you bring that up - I have another concern about dystrophin as well.  We know about the potential for immune response (http://www.nature.com/gt/journal/v7/n17/full/3301259a.html) - and yet I don't hear very much talk about it.   Are we setting ourselves up for a huge disappointment - plowing blindly forward when we don't even know if our boys' bodies will accept dystrophin?  I am curious why all of the companies that are doing exon skipping trials also aren't vigorously researching how to suppress the potential immune response.

Moein said:

I am afraid that ACE 031 can increase muscles but non functional.

Can anybody tell me why they didn't do strength assessment in healthy volunteers or even Exon Skipping?

I see that they are talking about the amount of dystrophin in Exon Skipping but they didn't mention if this dystophin functional or not!

Strength assessment was performed in exon skipping trials. AVI reported results, NO improvement in their UK dosing trial, the duration and/or the dose level might not be long enough. PRosensa/GSK also measured differnt things, they only reported increase in 6MWT in their Phase I/II trials.

 

I think that it is hoped that ACE-031 will produce some improvement in function after long term treatment, reduction in fibrosis while increasing lean muscle mass should have an effect on function people hope. I do think that 12 weeks is not nearly long enough for that. I am more concerned about side effects at this point thought and about the fact that the trial does not progress. They are analyzing that data for a while now...

Moein said:

I am afraid that ACE 031 can increase muscles but non functional.

Can anybody tell me why they didn't do strength assessment in healthy volunteers or even Exon Skipping?

I see that they are talking about the amount of dystrophin in Exon Skipping but they didn't mention if this dystophin functional or not!

Me too worried about the side effect of ACE and i am sure it will be helpful in long term.

 

Ofelia,

Any news about mini or micro dystrophin project of dr Mendell? Its been ages they are working on it. Are they going forward with it or not?

Thanks,

Amrit

They published a paper this year showing that they found immune response interfering with the newly produced dystrophin. The next step is to study how to handle the immune response. Their paper hinted that some boys are "predispose" to immune response but other researchers do not agree with this...not very clear at this point. IT's going to take many years to study this, definitely not soon enough for our boys.

Amrit said:

Me too worried about the side effect of ACE and i am sure it will be helpful in long term.

 

Ofelia,

Any news about mini or micro dystrophin project of dr Mendell? Its been ages they are working on it. Are they going forward with it or not?

Thanks,

Amrit

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