New long acting iron chelator ..40SD02, (starch-conjugating deferoxamine (S-DFO)

Hi everyone,

I found this interesting update on the ongoing research regarding Thalassemia.

The information about the up coming chelators is pretty impressive such as Starch-DFO which is a Desferioxamine(Desferal) molecule attached to starch. This makes it have a longer half life in blood that increases it's efficiency.

You can also check out more interesting research updates on the left side menu of the page

http://www.nyas.org/ebriefreps/main.asp?intSubsectionID=2704

Take care, Peace!

From:- http://www.cooleysanemia.com/bodies/body356.php

Starch Desferal Update

An article recently published in the British Journal of Haematology provides an update on the iron chelator 40SD02, (starch-conjugating deferoxamine (S-DFO), often referred to as “Starch Desferal”).

The article, entitled “Phase 1b clinical trial of starch-conjugating deferoxamine (40SD02): a novel long-acting iron chelator,” details the results of a single-dose trial conducted in 2002 and 2003 at Children’s Hospital Oakland and Weill Medical College of Cornell University/New York-Presbyterian Hospital.

Unlike regular deferoxamine, which is typically administered subcutaneously for an 8-12 hour period, 5-7 nights per week, Starch Desferal is designed to be administered intravenously for a shorter period of time and at significantly greater intervals, thereby providing a chelation option that maximizes potential for compliance. For this study, the drug was administered only one time, for one hour. Study subjects did not receive another dose or any other chelating agents for the one week they were involved in the trial.

16 individuals with beta-thalassemia were enrolled in and completed the trial. Four different dose levels – 150 mg/kg, 300 mg/kg, 600 mg/kg and 900 mg/kg – were tested, with four patients assigned to each level. (900 mg/kg is equivalent to 237 mg/kg of regular deferoxamine.)

Starch Desferal, which is created by attaching deferoxamine to a modified starch polymer, was found to be safe and well-tolerated within the parameters of this study. Four of the patients experienced a skin disruption(hives),which was judged as either mild or moderate.

The authors of the study concluded that “a single 60-minute infusion of S-DFO stimulated prolonged urinary iron excretion extending over several days. Mean 7-day urinary iron excretion (in mg elemental iron excreted per kg body weight) in the highest dose group (900 mg/kg) was 1.31 (range 0.79-1.93) mg/kg.” Although there was considerable variability in excretion between patients (as is often the case with other chelating agents), there did appear to be a linear dose-response relationship between the amount of drug given and the amount of iron excreted.

The authors suggest that some complications related to thalassemia may be closely related to non-transferrin bound iron (NTBI) in the blood and therefore that “…the presence of continuous chelating capacity in the circulation may be beneficial. S-DFO appears to provide such protection in a dose-dependent fashion with excess free iron-binding capacity in the circulation for more than 6 days, on average, in the high-dose group.”

Further studies are necessary to determine whether this period of excess chelating capacity in the plasma can be extended with repeat dosing and whether other measures support these initial results. The authors also suggested that “if continuous chelating capacity in the circulation can be maintained, S-DFO may be useful in ‘combined therapy’ intended to promote additive or synergistic excretion.”

The effect of S-DFO on stool iron excretion was not examined in this trial.

This study was sponsored by Biomedical Frontiers, Inc., a private biopharmaceutical company which is developing 40SD02.

Hope for the research to bring up the least painful Iron Chelators

BMF's drug is a long-acting iron-binding (chelating) compound that is targeted toward treatment of patients with b-thalassemia (Cooley's Anemia) and sickle cell anemia. Essentially all b-thalassemia and many sickle cell patients receive red blood cell transfusions to manage the disease, which inevitably leads to a massive build-up of iron in the body. In order to avoid the toxic and potentially life-threatening effects of this iron overload, these patients must undergo treatment to remove the excess iron. Current treatment requires slow infusions of an iron-binding drug over a period of 8 hours per day, at least 5 days per week. BMF's iron chelating drug is much longer acting, and is expected to provide a week's worth of treatment with a single short term infusion.

when i was searching for this drug , i red somewhere that it will b last longer than the desferal... soo patients will get benefit of short time chelation therapy ...  i will sugest you to check complete article ... its an old one 13 /2/2001 and i will try to find an updated one as well ...

for complete details :

http://www.chiesigroup.com/2007/eng/chiesi_informa/news_detail.asp?id=18

2007 Aug;138(3):374-81

to the link :
http://www.ncbi.nlm.nih.gov/pubmed/17614825?dopt=Abstract

Phase Ib clinical trial of starch-conjugated deferoxamine (40SD02): a novel long-acting iron chelator.

Harmatz P, Grady RW, Dragsten P, Vichinsky E, Giardina P, Madden J, Jeng M, Miller B, Hanson G, Hedlund B.

Department of Gastroenterology, The Children's Hospital & Research Center Oakland, CA, USA. pharmatz@mail.cho.org

The most widely used drug for iron chelation is deferoxamine (DFO) mesylate. While effective in promoting iron excretion, it requires prolonged daily infusions, often resulting in poor compliance. A clinical trial was conducted using starch-conjugated DFO (S-DFO; 40SD02), a high-molecular-weight iron chelator possessing prolonged vascular retention. Single doses of S-DFO were infused intravenously into groups of four transfusion-dependent patients with beta-thalassaemia at doses of 150, 300, 600 and 900 mg/kg. Urinary iron excretion and various pharmacologic parameters were evaluated for 1 week and safety for 3 weeks. No drug-related effects were observed on clinical chemistries, haematological and coagulation parameters, urinalyses, vital signs or electrocardiograms. Drug-related adverse events were limited to four urticarial reactions, none requiring termination of the infusion. The drug stimulated clinically significant urinary iron excretion, with the highest dose (900 mg/kg) inducing excretion of 1.31 mg of iron/kg (range 0.79-1.90 mg/kg) over 1 week, with residual iron-binding capacity present in the plasma for over 6 d. In summary, treatment with S-DFO, administered weekly, has the potential to achieve iron balance in the poorly compliant patient.

Publication Types:
Clinical Trial, Phase I

PMID: 17614825 [PubMed - indexed for MEDLINE]

900mg/kg!!!! That's huge to take in one day!

even though you're not taking it the rest of the week.

Even though the dose sounds high, S-DFO has a high molecular weight so it may be a lesser quantity than it seems. Also, the drug is taken IV and administration takes only one hour, once per week.

http://www.chori.org/Clinical_Studies/Thalassemia/TCRN_past_studies.html

Starch Desferal (S-DFO) is given IV over one hour and works chelating iron for one week because it is attached to a starch and is slowly released over time. In this study patients were given different doses to help find out what was the most effective dose of starch Desferal. Patients were asked to do various tests during the week after the infusion of S-DFO. Some patients did report hives during the infusion but none required stopping of the infusion. It was found that S-DFO given weekly has the potential to be an effective chelator.

Hi everyone....
Christine asked me to ask because she stll cannot log on to this site.....Lauryn is now 2 yrs old she turned 2 last week ...to date she has had 14 tx...last month her ferritin was in the 600's and now this month is a little over 1000...her dr wants to start chelating...Christine would like any information possible and should she start desferral or exjade?

thanks Kathleen

Hi Kathleen :
i hope you n both of your childrens will fine and happy there ...
i like to BELATED HAPPY BIRTHDAY TO LAURYN ...
secondly i wana come to your question : i think her doctor will not sugest exjade to her... bcoze she is too young for this medicine...( it's my gues ) ....but... wait for the response from Andy ..... he can guide you in right way.... or send PM to Andy for a quick response ...

Best Regard
Take Care
Umair

Exjade is approved for ages 2 and up in the US. My advice is to start out with a very low dose and slowly raise it in order to minimize side effects (this advice is extremely important for anyone starting on Exjade).

Hi andy :
thanx for correctiing my mistake andy ... u're too good