Retrospective Analysis on the Impact of Generic Immunosuppressants on Acute Rejection and Long Term Graft Survivals (U01)

Post Date

April 18th 2014

Application Due Date

June 21st 2014

Funding Opportunity Number

RFA-FD-14-021

CFDA Number(s)

93.103

Funding Instrument Type(s)

Cooperative Agreement

Funding Activity Categories

Health
Science and Technology and other Research and Development

Number of Awards

1

Eligibility Categories

State Governments
County Governments
City or Township Governments
Special District Governments
Independent School Districts
Public and State Controlled Institutions of Higher Education
Federally Recognized Native American Tribal Governments
Public Housing Authorities or Indian Housing Authorities
Non-Federally Recognized Native American Tribal Organizations
Non-Profits With 501 (c) (3) Status With The IRS (Except Higher Education Institutions)
Non-Profits Without 501 (c) (3) Status With The IRS (Except Higher Education Institutions)
Private Institutions of Higher Education
For-Profit Organizations (Except Small Businesses)
Small Businesses
Other

Foreign Recipients

Funding

• Estimated Total Funding:

  $2000000

• Award Range:

  $750000 - $1000000

Grant Description

Background: Survival after solid organ transplantation has increased substantially due in part to the broad clinical use of immunosuppressants. Immunosuppressive regimens typically include a combination of a calcineurin inhibitor (tacrolimus or cyclosporine), an antiproliferative agent (mycophenolate mofetil, mycophenolate sodium, or azathioprine), and corticosteroids. Proliferation signal inhibitors, e.g., sirolimus, may also be used either in combination with a calcineurin inhibitor or antiproliferative agent, or as a replacement for one. Availability of generic versions for these immunosuppressants allows for reduced drug costs that translate to increased drug access and significant cost savings for both insurers and patients. Maintenance of the immunosuppressive balance is critical for allograft patency, minimization of adverse effects, and ultimately long-term survival of solid organ transplant recipients. The question whether the brand to generic switch or switch among multiple generic products may introduce clinically relevant changes in drug exposure and thus affect acute rejection, adverse events, and long term graft survival remains debated in transplant community. To address transplant communityуs concern, FDA funded research studies to compare the pharmacokinetics (PK) of approved generic tacrolimus capsules to Prograf (brand product) in stable liver and kidney adult transplant patients with moderate and high immunological risk. However, the impact of introduction of generic immunosuppressants on long term graft survival was never systematically evaluated. These clinical outcome studies are critically needed to confirm the therapeutic equivalence of generic immunosuppressants with the brand product, thereby increasing transplant community confidence on the use of generic immunosuppressants. Objectives: The objective of this study is to conduct a retrospective analysis about the impact of generic immunosuppressants on short term acute rejection and long term patient graft survival since the introduction of generic immunosuppressants. The outcome of this study will help respond to public concerns regarding the interchangeability of generic immunosuppressants and improve review practices of generic immunosuppressants if necessary. The retrospective analysis will also aid in the design of prospective studies to investigate generic substitution for immunosuppressants. Detailed Descriptions: The model drugs to be studied should include at least cyclosporine, tacrolimus, mycophenolate mofetil, and mycophenolate sodium. The project may include the following: 1. Conduct a multi-center retrospective analysis of kidney, heart, liver transplant recipients using any model drug listed above. Data including demographic, immunosuppressive medications (drug, brand/generic, single/multiple generic), dosage level and adjustment, transplant organ function, acute rejection, renal/liver biopsy results and others should be collected from clinical databases, electronic medical records or other relevant databases. 2. Evaluate patient adherence to their immunosuppressant therapy 3. Perform acute rejection and long-term survival analysis (e.g., 1, 3, 5 or 10-year survival) of patients taking brand immunosuppresants only, generic immunosuppressants only, or both brand and generic immunosuppressants. Further subgroup analysis in children, adults, and African Americans is recommended. 4. Analyze other factors such as donor-, transplant-, and patient-related risk factors which may potentially affect long-term survival of patients.

Contact Information

• Agency

  Department of Health and Human Services

• Office:

  Food and Drug Administration

• Agency Contact:

  Gladys Melendez-Bohler
  Grants Management Officer/Specialist
  Phone 240-402-7565

• Agency Mailing Address:

  FDA Office

• Agency Email Address:

  gladys.bohler@fda.hhs.gov

• More Information:

  Copy of published RFA