In 2015, the Office of Hematology and Oncology Products (OHOP) approved 16 new molecular entities. The most notable were drug approvals in disease areas such as non–small cell lung cancer, colorectal cancer, breast cancer, melanoma, renal cancer, and diseases that are particularly difficult to treat such as pancreatic cancer.
This past year, we have made great strides in the treatment of multiple myeloma, approving daratumumab (Darzalex), elotuzumab (Empliciti), ixazomib (Ninlaro), and panobinostat (Farydak) to treat this disease. Other noteworthy achievements include the approval of the first biosimilar product in the United States, filgrastim-sndz (Zarxio), a bone marrow stimulant that helps the body make white blood cells after receiving cancer medications, and dinutuximab (Unituxin), which is part of a first-line therapy for pediatric patients with high-risk neuroblastoma.
November 2015 was a particularly busy month, with the approval of six new oncology drugs, the majority of which were approved using expedited review programs.
Expedited Programs and Review
The U.S. Food and Drug Administration (FDA) reviews new drug applications according to time frames established by the Prescription Drug User Fee Act. There are also programs in place to expedite the drug development and review timeline, and many of the innovative therapies that were approved by the OHOP this past year received an expedited designation. Generally, these designations are given to therapies that we consider to be better than what is currently on the market or that fulfill an unmet medical need. The accelerated approval, priority review, and breakthrough therapy programs are frequently used with new oncology drugs, and often a single drug receives multiple designations.
The OHOP frequently uses the accelerated approval pathway, which allows us to approve a drug based upon a surrogate endpoint or marker that is reasonably likely to predict a clinical benefit, such as an improvement in overall survival. Following an accelerated approval, companies conduct additional confirmatory clinical trials with the drug to further examine its clinical benefit. The use of surrogate endpoints and confirmatory trials shifts the lengthy analysis of survival to the postmarket setting and provides patients with earlier access to promising new drugs.
Another program used by the OHOP to expedite the approval of a drug is the priority review designation. This program is focused on drugs that treat serious and life-threatening diseases and, if approved, would provide a significant improvement in safety or effectiveness over available therapy. Applications receiving a priority review have a shorter time frame for review of the marketing application.
The newest program aimed at expediting the development of drugs for serious and life-threatening diseases is the breakthrough therapy designation. This program is designed for drugs where preliminary evidence indicates that the drug may demonstrate a substantial improvement on a clinically significant endpoint over available therapy. When a drug is granted breakthrough therapy designation, review offices such as the OHOP help expedite the development and review of the drug, often by having a more dynamic interaction with pharmaceutical companies with the intent to resolve any problematic issues as early as possible.
Why Oncology Drugs Receive Expedited Reviews
Expedited reviews or early actions are not a new phenomenon in oncology. One of the earliest expedited reviews for an oncologic drug was the approval of imatinib in May 2001 for chronic myeloid leukemia. The review and approval of imatinib occurred in approximately 2.5 months. In the past 5 years, approximately 60% of the OHOP’s new molecular entities approvals were ahead of the Prescription Drug User Fee Act time frame.
Over the years, oncology drugs have become “targeted agents” aimed at specific molecular pathways or targets involved in cancer growth. These drugs have been developed because of a greater basic scientific understanding of how cancers grow. Examples of targeted agents approved in 2015 include alectinib (Alecensa) and osimertinib (Tagrisso) for the treatment of specific types of lung cancer as well as the approval of cobimetinib (Cotellic) for the treatment of metastatic melanoma. Drugs aimed at a specific molecular target generally have greater effectiveness in a specific population and may generally have a more favorable benefit-risk profile.
Through the use of the expedited review programs and the commitment of [a variety of professionals], our aim is to provide the American public facing serious and life-threatening diseases with the latest advancements in the field while ensuring the safety and effectiveness of these drugs.— Richard Pazdur, MD
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Many other factors enable the OHOP to expedite the approval of an oncology drug, especially if the drug has an improved benefit and reduced risks. Newer drugs are demonstrating high response rates that are substantially better than those with presently available agents. This is particularly evident in drugs that have received breakthrough therapy designations.
Safety and Effectiveness With Expedited Approvals
I must emphasize that an expedited review or an early approval does not mean that the drug is any less safe or effective than one that is approved closer to or on its Prescription Drug User Fee Act date. Many of the OHOP’S oncologists are practicing physicians who assume the care of patients with cancer and understand the need to facilitate the approval of important drugs while maintaining the high standards of safety and effectiveness.
Early approvals are not at the expense of the quality of the review. Extra resources are allocated to the review of these applications by assigning multiple reviewers to an application, enhancing communication within the review teams and field inspectors, as well as providing greater communication with sponsors to quickly resolve issues that may arise during the review. This resource allocation planning often begins prior to the actual application being submitted to the FDA.
Working With the Cancer Community
Our goal is to keep making safe, innovative, and effective cancer treatments available for patients. The OHOP currently has several ongoing projects with advocacy groups and professional organizations to facilitate regulatory science aimed at getting safe and effective cancer therapies to patients faster.
We have held workshops with these groups to examine dosing of oncology drugs to optimize the effectiveness and reduce the toxicity of cancer drugs, ways of improving and facilitating access to unapproved drugs, as well as efforts to increase enrollment in clinical trials by expanding the eligibility criteria for these trials.
We work closely with other centers and offices throughout the agency as well as the National Cancer Institute. The OHOP also participates in a monthly teleconference with drug regulators from other countries to share ideas and concerns regarding various oncology drug applications.
The OHOP also plans to expand on the agency’s “patient voice” initiative. Over the next year, the OHOP will begin a project on patient-reported toxicity as a way to incorporate the patient’s perspective in the description of toxicity and the safety of cancer treatments.
Ensuring Safe and Effective Oncology Drug Products
In 2016, the OHOP will continue to conduct thorough reviews of oncology drug product applications and approve drugs that meet the agency’s rigorous standards. We have over 70 medical oncologists as well as pediatric oncologists, radiation oncologists, oncology nurses, physician assistants, and oncology pharmacists who participate in the clinical evaluation of safety and effectiveness of oncology drugs.
In addition, there are statisticians and basic scientists examining the clinical pharmacology and toxicology of these drugs as well as chemists involved in the review of manufacturing. Through the use of the expedited review programs and the commitment of these individuals, our aim is to provide the American public facing serious and life-threatening diseases with the latest advancements in the field while ensuring the safety and effectiveness of these drugs. ■
Disclosure: Dr. Pazdur reported no potential conflicts of interest.
