The accelerated approval pathway: Helping patients with serious or life-threatening diseases

Today, the House Energy & Commerce Committee’s Subcommittee on Health will meet to discuss policy proposals to “encourage innovation and improve oversight” regarding medical innovation. This hearing comes at the same time members of Congress are considering the reauthorization of the user fee programs, the Prescription Drug User Fee Act (PDUFA VII) and the Biosimilar User Fee Act (BsUFA III). The U.S. Department of Health and Human Services’ transmittal of the proposed PDUFA VII and BsUFA III packages to Congress in January marked the beginning of the legislative phase and an important milestone in the reauthorization process of these two user fee programs.

Among the policy proposals being considered at today’s hearing is legislation that could have a negative impact on the highly successful accelerated approval pathway. Established in the early 1990’s to address the HIV/AIDS crisis, the accelerated approval pathway has helped speed the availability of treatments for patients with serious or life-threatening diseases with significant unmet medical need while maintaining the U.S. Food and Drug Administration (FDA)’s high standards for safety and effectiveness.

Here is what you need to know about the accelerated approval pathway:

What is the accelerated approval pathway?
The accelerated approval pathway, formally established by FDA regulations in 1992 and later codified in statute in 1997, enables expedited access to medicines based on the medicine’s effect on a surrogate endpoint – a marker such as a laboratory measurement, radiographic image, physical sign or other measure. It is through a surrogate endpoint that FDA determines a medicine is reasonably likely to predict long-term clinical benefit, and FDA as a matter of course requires that sponsors of accelerated approval products conduct post approval studies to verify clinical benefit. Medicines approved under accelerated approval address unmet medical needs for serious and life-threatening diseases and conditions and meet FDA’s high standards for safety and effectiveness. This pathway has provided timely access to hundreds of treatments for HIV/AIDS, cancers and rare diseases, leading to better health outcomes for millions of patients.

How does the accelerated approval pathway help patients?
Simply put the accelerated approval pathway provides access to therapies faster than the traditional approval pathway. This ability for the FDA to approve products under accelerated approval has improved and even extended patients’ lives. One assessment of oncology treatments concluded that therapies receiving accelerated approval were made available a median of 3.4 years earlier than those approved through traditional approval with significant benefits for patients. In multiple myeloma, as an example, the FDA has noted that 10 of the medicines available on the market were approved under accelerated approval. As a result, according to FDA, “the average life expectancy for a common hematological malignancy is now anywhere between 8-10 years, when prior it was about two years” – “greatly due to drugs that were approved under accelerated approval.”

Since its inception, over 250 new drugs and biologics to treat serious or life-threatening illnesses have been approved through the accelerated approval pathway. From 1992 through about 2010, accelerated approval was primarily used for drugs indicated for the treatment of HIV (39.7% of approvals), cancers (35.6% of approvals) and other rare disease treatments and specialty drugs (24.7% of approvals).

Is the accelerated approval pathway any less rigorous than traditional FDA approvals?
No. A medicine approved under the accelerated pathway must meet the same standard of safety and efficacy for approval as medicines subject to traditional approval. However, as opposed to utilizing a direct measure of clinical benefit, clinical trials to support accelerated approval can be based upon measure of a surrogate endpoint—a marker such as a laboratory measurement, radiographic image, physical sign or other measure—or an intermediate clinical endpoint such as a symptom relief that is reasonably likely to predict clinical benefit.

For example, in clinical trials for cancer, where most accelerated approvals are currently granted, researchers can measure a medicine’s effect on tumor growth before observing an effect on survival or morbidity, which generally requires long, large clinical trials because of the duration of the typical disease course. When deciding whether a medicine is eligible for accelerated approval, the FDA requires substantial evidence of efficacy and bases its decision on whether to accept the proposed surrogate endpoint on the scientific support for that endpoint.

Could the FDA withdraw medicines approved under accelerated approval if post approval studies fail to verify clinical benefit?
Before approving any new medicine, the FDA determines whether it is safe and effective, and this applies to traditional and accelerated approvals alike. In addition, the FDA requires sponsors of accelerated approval products to conduct post-approval studies to verify the anticipated clinical benefit. The agency can use expedited procedures to withdraw a product or indication approved under the accelerated approval pathway based on a number of reasons, including if the post-approval studies fail to verify the predicted benefit. Of the 165 therapies that received accelerated approval over the last ten years, only six indications have been withdrawn, and an additional nine sponsors voluntarily withdrew their applications for accelerated approval indications.

Does PDUFA VII make changes to the accelerated approval pathway?
The upcoming PDUFA VII efforts are aimed at modernizing the U.S. regulatory and drug development paradigm and improving efficiencies in drug review. For example, FDA will update their review processes to provide timelier discussions between sponsors and the FDA to help ensure earlier agreement on postmarketing requirements, including for drugs and biologics approved under the accelerated approval pathway.

As Congress continues its consideration of PDUFA VII, we look forward to working with policymakers to ensure the successful accelerated approval pathway continues to support patients’ timely access to lifesaving medicines.

To learn more about the importance of the accelerated approval pathway, click here.