By: Janet Woodcock, M.D.
Everyone knows that different people don’t respond the same way to medications, and that “one size does not fit all.” FDA has been pushing for targeted drug therapies, sometimes called “personalized medicines” or “precision medicines,” for a long time.
Targeted therapies make use of blood tests, images of the body, or other technologies to measure individual factors called “biomarkers.” These biomarkers can then be used to determine who is most likely to benefit from a treatment, who is at higher risk of a side effect, or who needs a different dose. Targeting therapy can improve drug safety, and make sure that only people likely to have a good response get put on a drug.
Targeted therapies have gained public attention since President Obama announced a Precision Medicine Initiative in his most recent State of the Union address. This initiative will reinforce our work at FDA, where development of targeted drug therapies has been a priority since the 1990s. In 1998, FDA approved the targeted therapy, Herceptin (trastuzumab), offering new hope for many patients with breast cancer. High levels of a biomarker, known as “HER-2,” identified breast tumors that were more likely to be susceptible to this drug.
Since the approval of Herceptin, the development of targeted therapies has grown rapidly. FDA’s Center for Drug Evaluation and Research (CDER) approved 30 targeted therapies since 2012, including Kalydeco (ivacaftor), a targeted drug for cystic fibrosis. In 2014 alone, eight of the 41 novel drugs approved were targeted, including:
- Lynparza (olaparib) for the treatment of advanced ovarian cancer.
- Blincyto (blinatumomab) for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL).
- Harvoni (ledipasvir and sofosbuvir) to treat patients with chronic hepatitis C infection.
- Viekira Pak (ombitasvir, paritaprevir, dasabuvir and ritonavir) for the treatment of chronic hepatitis C infection.
- Cardelga (eliglustat) for the long-term treatment of Gaucher disease type 1.
- Beleodaq (belinostat) for the treatment of peripheral T-cell lymphoma.
- Zykadia (ceritinib) to treat patients with non-small cell lung cancer (NSCLC).
- Vimizim (elosulfase alpha) for the treatment of Mucopolysaccharidosis Type IV (Morquio Syndrome).
Since the 1990s, FDA has also been working on personalized drug dosing. People differ in how they eliminate a drug—some eliminate it much more slowly than most other people and are susceptible to overdosing, and others eliminate it much faster, and may not get any effect. There are biomarkers to identify people who have these unusual results, and CDER has been actively working for more than 15 years to put these findings into drug labels, so that each patient gets the correct dose, particularly for highly toxic or critically important drugs.
Personalized drug safety has also gotten attention. Often, one person experiences a serious side effect that does not affect thousands of others. Science is beginning to unlock the reasons for these rare toxicities, and the labels of some medicines advise screening people to make sure they are not at high risk for a severe side effect. This can make drugs much safer.
CDER has been recognized with awards from the Personalized Medicine Coalition and the Personalized Medicine World Conference for its longstanding work in this area.
CDER uses a lot of flexibility when reviewing applications for targeted drugs. Targeting people with a good chance of response means fewer people are eligible for a drug. CDER has adapted to the resulting small development programs. For example, among the targeted therapies approved in recent years, almost 60 percent were approved on the basis of one main clinical trial along with supporting evidence. In addition, 90 percent used one or more of FDA’s expedited programs such as Breakthrough, Fast Track, Priority Review and Accelerated Approval.
It is still hard to develop targeted therapies for many diseases, because there isn’t enough scientific understanding of why the disease occurs and what biomarkers would be useful. For many common illnesses, much more research is needed to reveal the individual differences that would enable development of targeted therapies.
We still have much work to do. However, we are pleased to see substantial progress and look forward to continuing our efforts to advance biomarkers, which will help bring additional important new therapies to patients in need.
Janet Woodcock, M.D., is Director of FDA’s Center for Drug Evaluation and Research