# ACE-031 info



## TwisT (Jun 3, 2011)

*Acceleron Presents Preliminary ACE-031 Results from a Phase 1 Multiple Ascending Dose Study in Healthy Volunteers*

*Cambridge, Mass.*  – October 13, 2010 – Acceleron Pharma, Inc., a biopharmaceutical  company developing novel therapeutics that modulate the growth of cells  and tissues including muscle, bone, fat, red blood cells and the  vasculature, today announced preliminary results from a Phase 1b study  to assess the safety,
tolerability and pharmacodynamic (PD) activity of *ACE-031* following multiple ascending doses in healthy postmenopausal volunteers. ACE-031 is an investigational Protein  therapeutic designed to build muscle and increase strength by blocking  proteins that inhibit muscle growth. In the trial, ACE-031 was generally  welltolerated with rapid and sustained effects on muscle, bone and fat.  Preliminary results from this randomized, placebo-controlled study were  presented at the 15th International Congress of the World Muscle  Society in Kumamoto, Japan.

The ACE-031 Phase 1b study (A031-02) randomized 60 healthy postmenopausal women 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 subcutaneous 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. Lean mass (measured by DXA scans) and  muscle volume of the thigh (assessed by MRI scans) were obtained at  baseline and weeks 5, 8 and 16. Other PD endpoints included biomarkers  of bone formation, bone resorption and fat metabolism, and measures of  muscle strength and function. Although this safety study was not powered  to assess statistically significant changes in these PD endpoints,  multiple exploratory statistical analyses were performed on the data  presented at the meeting. For a more detailed description of the study  design, visit clinicaltrials.gov and query study identifier NCT00952887.

“The preliminary results of this multiple dose study in healthy  volunteers confirm and expand upon the encouraging results observed  previously in the single dose study of ACE-031,” said Matthew Sherman,  MD, Chief Medical Officer of Acceleron. “These data are encouraging as  we continue the development of ACE-031 in the ongoing Phase 2 study in  patients with Duchenne Muscular Dystrophy.”

*Summary of Preliminary ACE-031 Phase 1b Study Results:*


*Safety, Tolerability and Pharmacokinetics:* ACE-031 was generally well tolerated at all dose levels. The most common adverse events (AEs) included injection  site reactions, headaches and nosebleeds. The majority of AEs were mild  and transient. ACE-031 had a half-life of approximately 12 days,  supportive of dosing every 2-4 weeks.
*Lean Mass:*  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.
*Muscle Volume:*  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.
*Bone Density:*  ACE-031 therapy led to a rapid and significant increase in a biomarker  of bone formation (BSAP) and decrease in a biomarker of bone resorption  (CTX) versus placebo. Consistent with these effects, lumbar spine bone  mineral density by DXA increased up to 3.4% in the 2 mg/kg every 4 week  group from baseline to day 113, compared with a decrease of 1.5% in the  placebo group (p=0.001).
*Fat:* ACE-031 treatment led  to significantly altered biomarkers of fat metabolism (increased  adiponectin and decreased leptin) by day 8. Total body fat mass measured  by DXA decreased up to 8.2% from baseline at day 113 in the 3 mg/kg  every 4 week group compared with an increase of 0.5% in the placebo  group (p=0.024).

*About ACE-031*

*ACE-031* is an investigational Protein  therapeutic designed to build muscle and increase strength by  inhibiting signaling through a cell surface receptor called activin  receptor type IIB (ActRIIB). ACE-031 is a recombinant fusion Protein  that is produced by joining a portion of the human ActRIIB receptor to a  portion of a human antibody. This creates a freely circulating, decoy  version of ActRIIB which interferes with proteins, such as GDF-8  (myostatin), that normally limit the growth and regeneration of muscle  by binding to and activating endogenous ActRIIB. Recent preclinical and  clinical studies with ACE-031 suggest that blocking signaling through  ActRIIB may be a way to increase muscle mass and improve muscle strength  and function. In a range of animal models of muscle disease, including  models of muscular dystrophy, muscle loss related to corticosteroid  treatment, androgen deprivation or advanced age, ACE-031 increased  muscle mass, strength and physical function. Unlike the mutation  specific RNA-based therapeutics in clinical development for Duchenne  Muscular Dystrophy (DMD), ACE-031 could potentially benefit patients  with DMD, irrespective of the underlying genetic mutation. ACE-031 is  being developed in collaboration with Shire.

*BUY ACE-031*


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## s2h (Jun 3, 2011)

this very well could be the next big thing.nice article.very interesting compound.


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## Thresh (Jun 5, 2011)

Is that 3mg per kg of body weight? (3mg/kg)


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## OutWhey (Jun 5, 2011)

pepman said:


> this very well could be the next big thing.nice article.very interesting compound.


 It is pepman. Not many people are carrying the ACE031 besides extreme peps. I hear the stuff incredible.


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## Thresh (Jun 13, 2011)

Thresh said:


> Is that 3mg per kg of body weight? (3mg/kg)



Bumping this question


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## ifxne (Aug 1, 2011)

2 months later....[crickets chirping]
there must be 100-200 people that have run this at low doses. we need to hear peoples' results.


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## CG (Aug 1, 2011)

Thresh said:


> Bumping this question


Yes it is


Sent from my SPH-M900 using Tapatalk


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## GMO (Aug 2, 2011)

Yes, and that is a hefty dose.  Sold in 1 mg, it would be quite costly to mirror those research dosages.  Definitely interested to see what a lower dose will do.


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## CG (Aug 2, 2011)

GMO said:


> Yes, and that is a hefty dose.  Sold in 1 mg, it would be quite costly to mirror those research dosages.  Definitely interested to see what a lower dose will do.



yeah seriously, even if we shot for the low range of the study, youre looking at .1mg/kg (say you weigh 220 lbs or 100kg.) thats .1mgx100kg, or 10MG - over a grand. OUCH - 

and thats just ONE dose


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## CG (Aug 2, 2011)

FML.
i have been thinking for quite some time that rat vs human studies are absolutely insane.

so i decided to do some research

my method of saying mg/kg for rats needs to be equal to that in humans is grossly wrong.. the good thing? shit just got alot cheaper (prospectively speaking, for future purchases) human equivalent is roughly 12.5 times *less* than rodent dose


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## ifxne (Aug 3, 2011)

And so we should be hearing about impressive gains. Is ACE 031 site specific at all?


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