FDA Innovation Brings New Therapies to Lung Cancer Patients

By: Richard Pazdur, M.D. and Gideon Blumenthal, M.D.

Last week, we approved a new drug for patients with a certain type of late stage, non-small cell lung cancer (NSCLC).

Richard Pazdur, M.D.

Richard Pazdur, M.D.

It’s one of four targeted therapies for lung cancer that have been approved since 2011—therapies that are the result of a new and forward-thinking approach to understanding the disease and its causes.

Within the last decade, the high quality of the data in the applications submitted to the agency and our collective understanding of the genetic and molecular underpinnings of lung cancer have enabled us to move from classifying the disease by what can be seen under a microscope, to looking at the patient’s molecular profile and classifying and treating the cancer by specific subtype. Scientists can now identify “driver oncogenes,” which cause a normal cell to become cancerous and promote the growth of a patient’s tumor. They can develop targeted therapies aimed at shutting down these aberrant genes and pathways, an example of an approach called personalized medicine.

Last week’s approval of Zykadia (certinib) provides a new treatment option for patients who comprise a relatively small subset of lung cancer and previously had few treatment options. While about 85 percent of lung cancers are NSCLC, making it the most common type, only about 5 percent of patients’ tumors are anaplastic lymphoma kinase (ALK) positive. Zykadia blocks this ALK protein that promotes the development of cancerous cells. In a clinical trial of 163 patients with metastatic ALK-positive NSCLC who had progressed on or were intolerant to a similar drug, results showed that tumors shrank in about half of the participants, and this effect lasted an average of seven months.

Gideon Blumenthal, M.D.

Gideon Blumenthal, M.D.

Moreover, the approval process exemplifies the important role of FDA and the strength of the collaborative process between FDA, industry, health advocacy organizations and other stakeholders. And it illustrates the dedication and enthusiasm of FDA reviewers who carefully, but expeditiously, analyzed complex study results to allow for earlier approval to support patient access to this new drug.

FDA granted breakthrough designation to this drug, thereby streamlining the development and review process with an “all hands on deck” approach. In fact, due to the enhanced understanding of ALK in lung cancer and the frequent interactions between the FDA and the commercial sponsor, it took less than four years—versus the roughly ten years it used to take—from the initial study of a drug to FDA approval.

We hope to further extend the collaborative effort in the future by participating in the use of the master protocol process. In a master protocol, multiple drugs and biomarkers can be tested in in a single, ongoing clinical trial. Under this approach, based on individual patient profiles, researchers can randomly assign patients either to one of several targeted treatments or to a control regimen of standard chemotherapy. We believe this will enhance the efficiency of clinical trials and help deliver safe and effective therapies to a patient population where few such therapies exist. Stay tuned: we hope to say more about this process in a future FDA Voice blog.

Of course, the progress we are making can’t come fast enough. There are far too many cancer mutations with few or no therapies developed thus far to treat them. But we and our colleagues throughout the medical research world are continuing to look for new and creative approaches to treat the disease. We’re well on our way.

Richard Pazdur, M.D. is Director of the Office of Hematology and Oncology Products at FDA.

Gideon Blumenthal, M.D. is the Team Leader of Thoracic Oncology in the Center for Drug Evaluation and Research at FDA. 

Counterfeit Drugs: Prosecuting the Profiteers, Protecting the Public Health

By: John Roth

On July 12, I was in Missoula, Montana when Paul Bottomley, 48, was sentenced as a result of his participation in the wholesale marketing of unapproved and misbranded cancer medications. Many Americans may not know Bottomley or his criminal activities. But his sentencing was another victory in FDA’s ongoing fight to safeguard Americans from misbranded, adulterated and counterfeit pharmaceuticals. This case is part of an agency-wide effort to ensure that consumers have access to high quality drugs – and that these medicines are traveling safely through increasingly complex supply chains.

Getting such predatory opportunists off the streets may be only a small part of what we do at the FDA’s Office of Criminal Investigations, but it is critical to protecting the public health. Our investigation found that Bottomley imported misbranded and unapproved cancer drugs from foreign countries – in violation of the Federal Food, Drug, and Cosmetic Act (FDCA) – and sold those drugs to American physicians.

Bottomley is one of those people you hope never to meet. He sold unapproved and misbranded cancer drugs through Montana Health Care Solutions (MHCS), which began operating in 2008.  In 2010, Bottomley sold MHCS to Rockley Ventures, a subsidiary of Canada Drugs, Ltd.,, but remained associated with the company as a consultant.  After its sale to Rockley, MHCS began selling Avastin, a prescription drug that at the time cost nearly $2,300 a vial, approximately $600 more than what MHCS charged.  In 2011, the Food and Drug Administration learned from the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) about a potential counterfeit oncology drug being marketed as Avastin. Our investigation led us ultimately to Bottomley, MHCS, and others.  Numerous physicians and the officials who operated their practices confirmed that the drugs they received came from MHCS.

Cancer patients in the United States count on certain drugs to treat their disease and often to keep them alive. Sadly, some of the Avastin sold by MHCS was counterfeit. In fact, when tested, the counterfeits did not contain any of the active drug ingredient bevacizumab that is found in legitimate versions of the drug. Tragically, not only did these patients pay a high price for a worthless drug, but they didn’t get the treatment they needed or expected.

But that is not all. In fact, one of the foreign sources of supply was Richard J. Taylor of Warwickshire, England. On July 11, 2012, Taylor was sentenced to 18 months in prison and a fine of $800,000 for distributing adulterated prescription drugs used for cancer treatment from the United Kingdom to multiple physicians in the United States. Like Bottomley, Taylor didn’t care about the law or the patients he was short-changing. He certainly knew what was happening to them. On May 10, 2011, Taylor was notified that two patients “who had been on Avastin for a while started to shake in the middle of being transfused and had to be disconnected from treatment.” A nurse advised that she had been administering such cancer drugs for years and had never seena patient react like this before.

Taylor and Bottomley both acted out of greed. In April, the U.S. Attorney for the District of Montana, Michael W. Cotter, made just that point, saying that Bottomley was motivated by nothing more: “Bottomley . . . sold potentially dangerous unapproved and misbranded pharmaceuticals at discounted prices to American physicians all for a healthy profit.”

All of us who work in enforcement at the FDA have seen this pattern too often – criminal offenders seeking to profit from distributing substandard or ineffective drugs that are ultimately administered to unsuspecting and vulnerable patients. So when people like Bottomley and Taylor are sentenced, we know this is a victory for all of us, especially those who are victimized by opportunists. OCI’s determined work continues to produce results. These prosecutions help deter others from such reprehensible conduct and from breaking the laws intended to protect us all.

FDA takes all reports of suspect counterfeits seriously and, in order to combat counterfeit medicines, is working with other agencies and the private sector to help protect the nation’s drug supply from the threat of counterfeits. Together, we are fighting a global battle, working with our regulatory counterparts throughout the world, utilizing new tools to safeguard the public health, and prosecuting those who seek to profit at the public’s expense.

John Roth is Director of FDA’s Office of Criminal Investigations

Setting the Bar High for FDA

By: Margaret A. Hamburg, M.D.

Rick Pazdur receiving ASCO Public Service Award

Rick Pazdur, accompanied by Margaret Hamburg, receiving ASCO Public Service Award

To say that Rick Pazdur faces enormous challenges in his job is an understatement. To say that he faces each day with energy, insight and resolve still falls short of the mark.

It’s my privilege to tell you that the American Society of Clinical Oncology (ASCO) has awarded Dr. Pazdur with its prestigious Public Service Award for his dedication to improving the lives of people living with cancer.

As director of the Office of Hematology and Oncology Products (OHOP) at FDA, Dr. Pazdur leads a staff of more than 130 oncologists, toxicologists and other specialists.

Their mission is making safe and effective drugs for cancer and hematologic (blood-related) conditions available to the patients who need them. The office is committed to facilitating rapid development, review and action on promising new treatments for these diseases.

Dr. Pazdur sets the bar high. His demand for excellence in his staff as well as in the treatments they review is unparalleled. Ultimately, Dr .Pazdur and his staff must decide whether or not an investigational drug can be tested in a clinical trial and, after testing, be approved for more widespread use. Sometimes, after careful investigation, they conclude that a drug has not been proven effective enough to outweigh the potential risks. These are the types of challenges and the tough decisions that Dr. Pazdur faces on a daily basis. A man of personal integrity with great compassion for those who are ill, he nonetheless is  often the recipient of criticism from patients, advocacy groups, drug companies and others. I have heard him say ruefully, but with characteristic humor, that you can’t win in this job—that if he approves a drug, he’s accused of lowering standards.  And if he doesn’t, he is insensitive to the plight of patients with cancer. Nothing could be farther from the truth.

Since his arrival at FDA in 1999, Dr. Pazdur has worked tirelessly to speed the development and availability of drugs that treat serious diseases, especially when the drugs are the first available treatment or have advantages over existing therapies. He has made a special effort to reach out to patient and advocacy groups, professional associations and foreign regulatory agencies. In 2012, nearly 40 percent of the new molecular entities approved in the Center for Drug Evaluation and Research were to treat cancer, often when few therapeutic options previously existed.

Members of Dr. Pazdur’s staff speak with warmth and enthusiasm of his dedication to cancer patients and his unflagging efforts to streamline the drug approval process. They call him not just a manager, but “a visionary,” and “one of the most unique people I know.” I quite agree.

To one of the most dedicated and accomplished people I know: It’s a pleasure to work at your side, Dr. Pazdur. Congratulations for this well-deserved honor.

Margaret A. Hamburg, M.D. is Commissioner of the Food and Drug Administration

We’re Working to Offset Ameridose Impact

By Margaret A. Hamburg, M.D.

Drug shortages are two words that no one wants to hear—not patients, not health care professionals, and not me.

Margaret Hamburg, M.D.FDA has been working hard to prevent and mitigate drug shortages. In 2011, the number of medications in short supply hit 251. Addressing drug shortages must be a top priority for us at FDA because these are medications that people need to stay healthy, to treat their illnesses, and even, in some cases, to stay alive.

This year, we’ve taken significant steps to expand our efforts and to engage in new ways with industry. Between Jan. 1 and Sept. 30, 2012, FDA worked with drug manufacturers to help avert the shortage of 145 drugs. Many critical medicines used to treat cancer and conditions such as attention deficit hyperactivity disorder (ADHD) are no longer in short supply.

However, drug shortages are still a serious problem, one that may be temporarily impacted by Ameridose LLC’s voluntary recall of all of its unexpired products. Ameridose, located in Westborough, Mass., is managed by some of the same people as the New England Compounding Center—which produced the drug that is implicated in the deadly, multi-state outbreak of fungal meningitis. An inspection of Ameridose was initiated as part of FDA’s ongoing investigation of the outbreak.

FDA recommended that Ameridose recall its sterile drugs because we could not be assured of the sterility of those products. However, this recall may affect supplies of certain life-saving drugs for some health care systems. FDA has identified a number of Ameridose products—including drugs used during surgery and to treat medical conditions that include congestive heart failure—that were on the current drug shortages list before the recall.

We also know that the supply of other drugs may be affected by the Ameridose recall. That’s why FDA is taking proactive steps to minimize the impact this recall may have on current drug shortages, and to prevent other shortages from occurring.

For recalled medications on the current drug shortages list, FDA is taking the same actions it has used successfully to mitigate other shortages.

  • FDA is working with manufacturers of these drugs, requesting that they ramp up production if they are willing and able to do so.
  • For any manufacturers of these drugs that may be experiencing manufacturing or quality problems, FDA is offering assistance to enable them to produce shortage drug products that are safe and high quality.
  •  As with shortages of any critical products, FDA will expedite the reviews of any pending applications that could help with addressing the shortages.
  • FDA is identifying any additional manufacturers willing to initiate or increase production.
  • If manufacturers of critical drugs are not able to meet U.S. patient needs, FDA will explore overseas companies that are willing and able to import foreign drugs to address the shortage. In these instances, FDA evaluates the imported drug to ensure that it is of adequate quality and that the drug does not pose undue risks for U.S. patients.

Since the beginning of the year, the number of advance notifications to FDA of potential shortages has greatly increased. If we know that a problem is on the horizon, we’re able to proactively work with industry, organizations, patients and stakeholders to address it. We have doubled the number of staff members who work in drug shortage prevention and response.

We at FDA are committed to doing everything we can, using all available tools, to prevent or mitigate drug shortages and help keep critically needed products on the market.

Margaret A. Hamburg, M.D., is Commissioner of the U.S. Food and Drug Administration.

Treating Children with Cancer

September is National Childhood Cancer Awareness Month. Watch the below video in which two FDA experts discuss existing and new efforts to encourage the development of medicines for kids with cancer.

The conversation is between Robert “Skip” Nelson, M.D., Ph.D., deputy director and senior pediatric ethicist in FDA’s Office of Pediatric Therapeutics, and Gregory Reaman, M.D., associate director of the Office of Hematology and Oncology Products.

It begins with a discussion of FDA’s role in evaluating medications used to treat children with cancer and what measures are underway to encourage further development of these important drugs.

For More Information


New Pediatric Labeling Information Database

Cancer Liaison Program

Office of Hematology and Oncology Products

Friends of Cancer Research Honors Our Dr. Richard Pazdur

By: Margaret Hamburg, M.D.

One of the privileges of being the head of the Food and Drug Administration is being able to report on the accomplishments of the dedicated and highly skilled employees who are advancing the public health mission of our agency. Last night, I had the pleasure of participating in an event honoring one of our scientists for work that makes us particularly proud: his outstanding contribution to the fight against cancer.

Margaret Hamburg, M.D. and Richard Pazdur, M.D.Dr. Richard Pazdur, the director of our Office of Hematology and Oncology Products, joined Senator John McCain and Neera Tanden, president of the Center for American Progress, as a recipient of the Cancer Leadership Award from the Friends of Cancer Research, an important organization that helps advance medical progress.

Senator McCain and Ms. Tandem have been tireless advocates for public investment in cancer research, getting cancer drugs to market more quickly, and developing prevention strategies that are known to reduce the risk of cancer. Dr. Pazdur, who was honored for his leadership in cancer research, makes sure that the drugs used to treat cancer patients are not only available for patients who need them as fast as science will allow, but above all, that they are safe and effective.

Achieving these three goals requires highly sophisticated and frequently very difficult decisions. Thanks to Dr. Pazdur, who arrived at FDA more than a decade ago as a highly regarded physician and researcher, our agency is up to the task. He has helped make FDA a more transparent, innovative and compassionate organization grounded in solid science.

At FDA, we appreciate both his professional and personal qualities. As an FDA official and scientist, Dr. Pazdur explores hard data with industry, academia, and patient advocates in search of innovative approaches to expediting the approval of new drugs. When talking to cancer patients and their advocates, Rick Pazdur, the physician, responds with deeply-felt empathy. But even this great compassion does not weaken his resolve to perform his foremost duty, which is to ensure that the benefits of cancer drugs are not outweighed by their risks.

Dr. Pazdur’s leadership is a hallmark of FDA’s pursuit of science in the service of public health. I am proud to congratulate him on his richly deserved award on behalf of our entire agency.

Margaret Hamburg, M.D., is Commissioner of the U. S. Food and Drug Administration