Shopping Cart
Your Cart is Empty
Quantity:
Subtotal
Taxes
Shipping
Total
There was an error with PayPalClick here to try again
CelebrateThank you for your business!You should be receiving an order confirmation from Paypal shortly.Exit Shopping Cart

The Venture 17 Division Of Education



THE CONSERVATORY OF MEDICAL ARTS AND SCIENCES

XVII

THE SEARCHLIGHT MESSENGER

Blog

Von Willebrand Disease Phase 3 Trial Reports 100% Bleed Control

Posted on August 12, 2015 at 11:02 AM
Von Willebrand disease (VWD) is an inherited, genetically and clinically heterogeneous hemorrhagic disorder caused by a deficiency or dysfunction of the protein called Von Willebrand factor (VWF). This protein is a necessary step in the coagulation cascade, but also involved in the initiation of platelet aggregation for proper blood clotting.

Consequently, defective VWF interaction between platelets and the vessel wall impairs primary hemostasis. Von Willibrand factor circulates in blood plasma at concentrations of approximately 10 mg/mL. In response to numerous stimuli, VWF is released from storage granules in platelets and vascular bed endothelial cells.

VWF performs two major roles in hemostasis, wether intrinsic or extrinsic. First, it mediates the adhesion of platelets to sites of vascular injury. Second, it binds and stabilizes the procoagulant protein factor VIII (FVIII).

The disease is divided into three major categories: Partial Quantitative Deficiency (type I), Qualitative Deficiency (type II), and Total Deficiency (type III). VWD type II is further divided into four variant conditions (IIA, IIB, IIN, IIM), based on characteristics of dysfunctional VWF.

According to data pre-published online August 3rd, 2015, in Blood, successful management of bleeding episodes were observed in 100% of subjects treated with BAX 111 for von Willebrand disease (VWD) during a recently completed Phase 3 clinical trial.

Bleeding-episode-management success was the primary endpoint of the clinical trial.
BAX 111 is a highly purified recombinant von Willebrand factor (VWF) analog manufactured by Baxalta, Inc.
VWD is a rare, inherited, incurable, gene-based bleeding disorder in which a missing or defective clotting protein (VWF) fails to bind with platelets in blood vessel walls.

Normally, a blood-vessel tear initiates bleeding and  VWF assists in the repair. When VWF is absent or under-represented, the formation of platelet plugs are inhibited during the clotting process, resulting in excessive bleeding and easy bruising.

In more severe forms of VWD, the bleeding can be life-threatening and require emergency treatment.

Efficacy and Safety of BAX 111

Gill et al derived their findings from a Phase 3, multicenter, international, open-label study which evaluated the safety, efficacy and pharmacokinetics of BAX 111 in 37 patients with severe VWD.
Study participants evidenced a mean efficacy rating of < 2.5 on a 4-point scale wherein lower numbers correlated with a higher degree of bleed control (see sidebar below). Bleed control for all treated bleeding events (N=192 bleeds in 22 subjects) was rated as good or excellent (96.9% excellent; 119/122 minor, 59/61 moderate, and 6/7 major bleeds). In 81.8% of bleeds, 1 infusion was sufficient to attain control. For major bleeds, the infusion median was

Sidebar: Hemostatic Efficiency Rating Scale

1 (Excellent)
 
• Minor and Moderate Bleeding Events
o Actual number of infusion less than or equal to estimated number of infusion required to treat that bleeding episode. No additional VWF-containing/coagulation factor containing product required.
• Major Bleeding Events
o Actual number of infusion less than or equal to estimated number of infusion required to treat that bleeding episode. No additional VWF-containing/coagulation factor containing product required.

2 (Good)

• Minor and Moderate Bleeding Events
o 1 to 2 infusions greater than estimated required to control that bleeding episode. No additional VWF-containing/coagulation factor containing product required.
• Major Bleeding Events
o Less than 1.5x greater than estimated required to control that bleeding episode. No additional VWF-containing/coagulation factor containing product required.

3 (Moderate)

• Minor and Moderate Bleeding Events
o 3 or more infusions greater than estimated used to control that bleeding event. No additional VWF-containing/coagulation factor containing product required.
• Major Bleeding Events
o Greater than or equal to 1.5x greater than estimated used to control that bleeding event. No additional VWF-containing/coagulation factor containing product required.

4 (None)

• Minor and Moderate Bleeding Events
o Severe uncontrolled bleeding or intensity of bleeding not changed. Additional VWF-containing/coagulation factor containing product required.
• Major Bleeding Events
o Severe uncontrolled bleeding or intensity of bleeding not changed. Additional VWF-containing/coagulation factor containing product required.References:
 
Safety and tolerability outcomes - evaluated via clinical assessments of adverse events, hematology panels, coagulation panels, serum chemistry, urinalysis, viral serology and immunological assessments - were also encouraging. With the exception of 1 patient, adverse events were minor or unrelated to treatment. No thrombotic events or severe allergic reactions occurred, and none of the participants developed anti-VWF binding or neutralizing antibodies to VWF.

Researchers concluded that the data offer evidence that BAX 111 is “safe and hemostatically effective in severe VWD patients in a variety of clinical bleeding presentations.”

Addressing a Pressing Therapeutic Need

“Von Willebrand disease is the most common hereditary bleeding disorder, yet few treatment options exist,” noted John Orloff, MD, Head of Research & Development and Chief Scientific Officer, Baxalta. BAX 111, Dr. Orloff asserted, “has the potential to transform the standard of care for patients with severe von Willebrand disease by offering an effective, individualized treatment option.”

Both the FDA and the European Medicines Agency granted orphan drug designation to BAX 111 back in November 2010.2 Currently, BAX 111 remains under FDA review, a pending Biologics License Application having been filed in December 2014.5 While no official Prescription Drug User Fee Act (PDUFA) date has been set, December 22, 2015, has been cited by industry insiders as a speculative estimation.

The PDUFA date is an FDA approval deadline for new drugs. If approved, BAX 111 would become the first recombinant replacement treatment indicated for the management of VWD-related bleeding episodes.

References
  1. Gill JC, Castaman G, Windyga J, et al. Hemostatic efficacy, safety and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease. Blood 2015. DOI 10.1182/blood-2015-02-629873. http://www.bloodjournal.org/content/bloodjournal/early/2015/08/03/blood-2015-02-629873.full.pdf?sso-checked=true Advance copy pre-published online August 3, 2015. Accessed online August 4, 2015.
  2. Blood Publishes Phase III Data on Baxalta’s Investigational Treatment for Von Willebrand Disease, the Most Common Type of Inherited Bleeding Disorder [press release]. Deerfield, Illinois. Baxalta Incorporated August 3, 2015. http://www.businesswire.com/news/home/20150803005068/en/Blood-Publishes-Phase-III-Data-Baxalta%E2%80%99s-Investigational#.VcCXYfmUf4Z
  3. National Hemophilia Foundation website. von Willebrand Disease. https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Von-Willebrand-Disease Accessed August 4, 2015.
  4. National Heart, Lung and Blood Institute. What is von Willebrand Disease? http://www.nhlbi.nih.gov/health/health-topics/topics/vwd Updated June 1, 2011. Accessed August 4, 2015.
  5. Burden A. Large cap PDUFA dates have been added to BioPharmCatalyst. http://www.biopharmcatalyst.com/2015/01/large-cap-pdufa-dates-have-been-now-added-to-biopharmcatalyst-20-in-total-today/  BioPharmCatalyst. Published January 26, 2015. Accessed August 4, 2015.



Categories: Clinical Update

Post a Comment

Oops!

Oops, you forgot something.

Oops!

The words you entered did not match the given text. Please try again.

414 Comments

Reply we do your essay
8:22 PM on July 4, 2017 
Medical science is the science of dealing with the maintenance of health and the prevention and treatment of disease, bioscience, life science any of the branches of natural science dealing with the structure of living organism, however essay writing services enhance our understanding about it.
Reply myessayslab
7:48 AM on August 15, 2017 
Wow! Interesting article/ I found a lot of useful information for my research. Thanks for sharing.
Reply Essays Mama
6:31 AM on November 22, 2017 
This article is so helpful for the bio students. You give the complete information about the blood nature and flow of the blood. I read this article so carefully and I really like this whole information. As a student, this is so helpful.
Reply art news agency
8:37 AM on December 6, 2017 
Very detailed and helpful article. I don't have any personal experience with that (and I hope it will stay this way) but it is always good to know something new and useful. Thank you for posting!
Reply AllfinancialStuff
7:34 AM on September 11, 2018 
great Post
Reply HarrySRogers
12:47 PM on December 8, 2018 
Thank for sharing this awesome post love to read this. AndroVid live nettv CShare
Reply picbear
6:28 AM on April 9, 2019 
Great Information,it has lot for stuff which is informative.I will share the post with my friends.
Reply bestessays
6:28 PM on June 23, 2019 
Sounds dangerous. At least I am informed about this disease now. I appreciate it.
Reply Teknoloji Haberleri G&#252;ncel
9:07 AM on September 8, 2019 
Wow nice post nice blog thank you for sharing!
Reply investering
4:18 PM on October 21, 2019 
Awesome substance material and extraordinary design. Your site merits the greater part of the positive input it's been getting.
Reply Get Microsoft Certification Exams Dumps
11:46 AM on January 13, 2020 
Selecting Get Microsoft Certification Exams Dumps for my guidance proved worth every penny!
Reply hermes online
6:23 AM on August 23, 2021 
Thanks for every one of your effort on this web page. Kate delights in getting into research and it's easy to see why. A lot of people know all concerning the lively means you render important tactics on this web blog and as well foster contribution from others on the subject matter and our own girl has been learning a lot. Take pleasure in the rest of the year. You're performing a useful job.
hermes online http://www.hermesonlineshop.com
Reply yeezy 500
6:24 AM on August 23, 2021 
I intended to post you one bit of note just to say thanks a lot once again just for the splendid things you have discussed here. It's really strangely generous of you giving unhampered just what many individuals might have advertised for an e book to help with making some cash for their own end, specifically given that you could possibly have done it in case you considered necessary. These smart ideas likewise acted like a good way to know that someone else have the same dreams like my own to figure out a little more in respect of this matter. I think there are numerous more enjoyable opportunities ahead for people who scan your blog.
yeezy 500 http://www.yeezy-500.us.com
Reply lebron james shoes
6:25 AM on August 23, 2021 
I must express some appreciation to this writer just for bailing me out of this particular condition. After searching throughout the internet and meeting principles which were not powerful, I assumed my life was well over. Being alive without the answers to the issues you have fixed by means of your good short post is a crucial case, and ones that could have adversely affected my career if I hadn't discovered your web site. Your personal talents and kindness in maneuvering the whole lot was crucial. I am not sure what I would have done if I hadn't discovered such a subject like this. I can also at this time relish my future. Thanks a lot very much for your specialized and effective guide. I will not think twice to suggest your web site to any person who needs recommendations about this topic.
lebron james shoes http://www.lebron18.net
Reply yeezy boost 350
6:26 AM on August 23, 2021 
I and my friends came looking at the excellent solutions located on your site and then all of a sudden came up with an awful feeling I never expressed respect to the blog owner for those strategies. The women had been totally joyful to read through them and already have surely been loving those things. Appreciation for turning out to be well accommodating and then for going for such nice guides most people are really needing to know about. Our own sincere regret for not expressing appreciation to you earlier.
yeezy boost 350 http://www.yeezy-350.us.com
Reply birkin bag
6:26 AM on August 23, 2021 
I precisely had to appreciate you again. I am not sure the things I would've done in the absence of the entire advice provided by you on my concern. It had become a alarming circumstance for me, nevertheless spending time with a specialised mode you processed the issue took me to cry with contentment. I will be grateful for the assistance and in addition expect you know what an amazing job you are carrying out educating the others all through your webblog. I know that you have never met all of us.
birkin bag http://www.birkinbag.us.com
Reply supreme outlet
6:27 AM on August 23, 2021 
I as well as my buddies ended up viewing the great strategies from your web site and then developed a terrible feeling I had not thanked the blog owner for those tips. Most of the boys came as a result joyful to see all of them and already have in reality been having fun with those things. Thanks for really being simply thoughtful as well as for using this form of important resources most people are really needing to discover. Our honest apologies for not saying thanks to you sooner.
supreme outlet http://www.supremeoutlet.us.com
Reply supreme shirt
6:28 AM on August 23, 2021 
A lot of thanks for every one of your efforts on this website. My mother enjoys engaging in investigation and it is simple to grasp why. Most of us know all regarding the powerful manner you offer informative thoughts via the blog and even foster contribution from other ones about this matter then my simple princess is in fact becoming educated a great deal. Take pleasure in the remaining portion of the new year. You're the one carrying out a really good job.
supreme shirt http://www.supremeshirt.us.com
Reply yeezy
3:01 PM on August 23, 2021 
I needed to put you the tiny remark to help give many thanks as before considering the breathtaking principles you've contributed on this site. This has been simply remarkably open-handed with you to provide without restraint what exactly a lot of folks would've advertised as an ebook to make some profit on their own, most notably given that you might have done it in the event you considered necessary. These tricks also served as a great way to comprehend some people have similar dreams like my personal own to learn more on the topic of this issue. Certainly there are thousands of more pleasant moments up front for folks who looked at your blog post.
yeezy http://www.yeezy-700.com
Reply kevin durant shoes
3:01 PM on August 23, 2021 
I enjoy you because of all of your hard work on this web page. Kate enjoys going through investigations and it's really easy to see why. My partner and i learn all about the powerful form you present worthwhile items through your web blog and as well attract contribution from website visitors on the situation so our princess is understanding a lot. Take pleasure in the remaining portion of the new year. You are always conducting a first class job.
kevin durant shoes http://www.kd12.us.com