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Review for Pharmacovigilance Planning -Atryn




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Memorandum

Subject: BLA STN 125284/0
 Antithrombin alpha (Atryn)
 OBE/DE Mid-cycle Review for Pharmacovigilance Planning 

To: Pratibha Rana, Regulatory Project Manager, OBRR 

From: Faith Barash, MD, MPH
 Therapeutics and Blood Safety Branch (TBSB)
 Division of Epidemiology (DE),
 Office of Biostatistics and Epidemiology (OBE) 

Through: Craig Zinderman, MD , MPH Acting Chief, TBSB, DE, OBE 

Background

OBE/DE has completed an initial review of BLA STN 125284/0 for Antithrombin 
alpha (Atryn) from GTC Biotherapeutics, Inc. Atryn is a nanofiltered, sterile, 
terminally heat treated lyophilized dosage form of recombinant antithrombin III. 
Atryn is produced by recombinant DNA technology, using genetically engineered 
goats into which the gene for human antithrombin has been introduced along with 
a mammary gland specific promoter which directs expression of the protein in 
milk.

The proposed proprietary and nonproprietary names are Atryn and Antithrombin 
alpha, respectively. Since Atryn is recombinant antithrombin III, it.actually 
contains both a and b forms of antithrombin.

Atryn contains 1750 international units of antithrombin per vial and is intended 
for intravenous infusion following reconstitution with 10 ml of sterile water 
and subsequent dilution into .9% sodium chloride. Atryn is not produced from 
human blood, nor is it formulated with human serum or plasma proteins. The 
genetically engineered goats used to express Atryn are USDA certified 
scrapie-free and pathogen-free.

Aytryn is indicated for use in hereditary antithrombin deficient patients for 
the prevention of peri-partum and peri-operative thromboembolic events. The 
dosage is individualized for each patient, with a goal of restoring and 
maintaining functional antithrombin activity levels between 80-120% (0.8-1.2 
IU/mL) of normal, to reduce the risk of thromboembolic events, as well as for 
treatment of such events.

Safety Surveillance Data

There is no post-marketing safety surveillance data available. Section 2.7.4, 
Summary of Clinical Safety, details the adverse events that were observed in 
clinical trials for this product. No evidence for overdosage was reported in 
clinical studies.

Pharamcovigiliance Recommendations

For most products, routine pharmacovigilance (i.e., compliance with applicable 
post-market reporting requirements under FDA regulations) is sufficient for 
post-marketing risk assessment. The ICH E2E Pharmacovigilance Planning guidance 
indicates that for products with important identified risks, important potential 
risks, or important missing information, additional actions designed to address 
these concerns should be considered as part of a pharmacovigilance plan 
(http://www.fda.gov/cber/gdlns/ichpvp.htm). The pharmacovigilance plan is 
developed by a product’s sponsor and is specifically focused on detecting new 
safety risks and/or evaluating already identified safety risks. As outlined in 
Guidance for Industry: Good Pharmacovigilance Practices and 
Pharmacoepidemiologic Assessment (http://fda.gov/CDER/guidance/63590CC.htm), FDA 
believes pharmacovigilance plans may be appropriate when: 1) Serious safety 
risks have been identified pre- or post-approval, or 2) at risk populations have 
not been adequately studied.

Adverse Event (AE) information collected in the clinical studies conducted for 
ATryn involves a limited number of exposed patients. In addition, there is a 
lack of post-market experience on which to base safety assessment beyond the 
safety database gathered in clinical studies, and the protein is derived from a 
novel source (genetically engineered animal) for a marketed therapeutic product. 
When a new product is marketed, the exposed population usually differs 
quantitatively and qualitatively from the population studied in pre-approval 
trials. The number of patients exposed is much larger, usage generally expands 
to unlabeled indications, and exposed patients have a broader array of 
demographic features, co-morbid conditions, and concomitant medical product use. 
AEs may occur that were not detected in the smaller, more homogeneous study 
populations.
  We recommend that the sponsor address potential safety issues in a 
  pharmacovigilance plan per ICH E2E Pharmacovigilance Planning guidance to be 
  submitted during the BLA review process so the plan can be ready for 
  implementation if the product is licensed.
  Please provide any adverse events reported as a result of recent post-market 
  experience in Europe.
  The sponsor has indicated that they (or their partners) have initiated a 
  controlled Phase II clinical trial to examine the safety and efficacy of Atryn 
  in patients with disseminated Intravascular Coagulation associated with severe 
  sepsis. Please provide any adverse events reported as part of this sepsis 
  study.
 

 


Key Resources

  Approval History, Letters, Reviews and Related Documents - ATryn	[ARCHIVED] 
      
 


More inFractionated Plasma Products
   


Resources for You

  Approval History, Letters, Reviews and Related Documents - ATryn	[ARCHIVED] 
  ATryn 
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