FDA's Patient-Focused Drug Development Program

Background on PDUFA and Patient-Focused Drug Development Program

The FDA's Prescription Drug User Fee Act (PDUFA) authorizes the FDA to collect fees from companies that produce certain human drug and biological products. These fees are used to expedite the drug approval process. The law was first enacted in 1992 and renewed most recently in 2012 (PDUFA V). The FDA information page on PDUFA can be found here.

A key provision of PDUFA-V is to improve drug development and review by taking a more systematic approach to looking at benefit-risk assessment for new drugs that considers disease severity and unmet medical needs. The Patient-Focused Drug Development Initiative allows the FDA to choose 20 different disease areas for concentration. Over the next 5 years, the FDA will conduct quarterly public meetings for each of the chosen diseases. Topics discussed will include:

• the impact of the disease on patients
• the spectrum of severity for those who have the disease
• the measures of benefit that matter most to patients, and
• the adequacy of the existing treatment options for patients

These meetings will include participation of FDA review divisions, the relevant patient advocacy community, and other interested stakeholders. In determining the disease areas that will be addressed in these meetings, FDA has published a preliminary list of nominated diseases and is inviting public comments on the list. The list currently does not include inherited cancer syndromes. A slide-show on Patient-Focused Drug Development can be viewed here.

FORCE in partnership with advocacy groups representing other hereditary cancer syndromes supplied oral and written testimony to the FDA for the inclusion of hereditary cancer syndromes to be included under the list of disease states which would receive special consideration. Please read our comments and contact the FDA in support of this designation for all inherited cancer syndromes.

FORCE's recommendations

The following is a summary of our recommendations to the FDA. You can read our full comments with justification for each suggestion here.

We urged the FDA to add hereditary cancer syndromes to the list of disease priorities in the patient-focused drug development initiative. The hereditary cancer community bears a heavy cancer burden. It’s time to remedy this disparity while optimizing the promise of personalized medicine. Below is a discussion of reasons why we believe that hereditary cancer syndromes should be included as a disease focus by the FDA:

Hereditary cancer treatment and pharmacoprevention offer unique opportunities for exploiting the
known gene defects and associated genes to develop population-specific treatments and preventions.
However, they also offer distinct challenges including the fact that hereditary cancers are rarer and
consist of a smaller subset of the larger cancer cohort. As such:

• There are fewer financial incentives for pharmaceutical companies to target these cancers vs. the larger disease population.
• Patients with hereditary cancer are motivated to participate in clinical trials and registries.
• However, they often enroll in studies that focus on sporadic cancers because of the number and
  availability of these larger, less targeted studies. This leads to a vicious cycle where fewer
  pharmaceutical companies are willing to develop drugs due to recruitment challenges.
• Tests to identify and define members of hereditary cancer populations create their own challenges to
  therapeutic development because they are often expensive, lack FDA approval or simply aren’t utilized.

Nevertheless, it is important to develop new preventive and therapeutic agents for those with inherited cancer because of their unique challenges:

• The lifetime risk for familial cancer is significantly higher, and cancers often strike younger and
  are more aggressive than sporadic cancers. This may lead to a different risk-benefit ratio for
  prevention and treatment than for sporadic cancers.
• The genes and pathways associated with these cancers are frequently known, lending the opportunity to target vulnerabilities that may not exist for sporadic cancer.
• Currently, risk-management for hereditary cancer syndromes focuses on cancer screening and surgical interventions. Many inherited cancers, including ovarian and pancreatic cancer, have no good early detection and a high mortality rate. Development of drugs explicitly to prevent cancers in individuals with hereditary cancer syndromes is achievable and could save thousands of lives and dollars per year.
• Hereditary gene mutations are sometimes associated with different risks and benefits for therapeutic agents compared with published standard-of-care for sporadic cancers. Much more needs to be learned about “standard therapy” in these specific populations and how to develop protocols that don’t expose patients to increased harm. For example:
  • BRCA mutation carriers may be more sensitive to the heart damaging effects of Adriamycin, a standard breast cancer chemotherapy agent;
  • 5-FU, a mainstay of standard chemotherapy for colon cancer, works only for some patients with Lynch Syndrome;
  • People with Li Fraumeni may be more sensitive to radiation therapy; and
  • Individuals with Ataxia-Telangiectasia cannot receive standard radiation or chemotherapy because they are extremely sensitive to the cytotoxic effects associated with these therapies.

 

Page updated 11/02/12

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