Richard's Blog

Post date: September 1, 2011

My First ODAC (Oncologic Drug Advisory Committee)

While being a patient representative for the FDA is very rewarding, it can also be somewhat maddening. The runway to any real participation is long, and the waiting can be a tad frustrating; not because there is any expectation that you should be participating quickly, but because you want to. So, when I finally did receive my first call to participate, I immediately said, “Yes, I’ll be there,” without even looking at a calendar. (I am fortunate to run my own business, so checking with the boss is an easy thing to do.)

White Oak Campus

White Oak Campus

The affirmative answer puts a few wheels into motion, which include the signing of financial disclosure forms, as to rule out any conflicts of financial interests with the presenting pharma company and a review of the rules of non-disclosure. Later, I received a package with discs containing confidential data about the drug the committee will be meeting to review, (in this case, BLA 125399, with the proposed trade name ADCETRIS (brentuximab vedotin)) as well as the findings of the FDA and a lengthy technical profile of the drug from the pharmaceutical manufacturer, (for Adcetris, Seattle Genetics). Prior to the meeting most of the information is fairly restricted, but by the time its over, it is public news, as you will see.

There is a fairly lengthy process of reservations being made, flights, transportation and hotels, and another primer on what the government will and will not pay for. (No drinks, no meals outside of the meeting day, and pretty much anything else you might think of.) There is a schedule of events for the day of the big show and plenty of contact information just in case you have any questions, which you shouldn’t, but I did. Then, more waiting.

I honestly didn’t have a great idea of what to expect. When I did my orientation, there were a few veterans who told us how things worked and a bit about what to expect, but I honestly couldn’t picture it. Apparently, in the case of the ‘bigger picture’ drugs, like Avastin, these proceedings can be quite profound and have the atmosphere of a big courtroom trial. Our drug had none of the controversy, so I just had no idea.

FFDA Buildig One

FDA Buildig One

We were examining Adcetris for use in two fairly small patient populations; in my meeting, we were evaluating its use in treatment of patients with relapsed or refractory systemic Anaplastic Large Cell Lymphoma, (ALCL) and in the morning session they were evaluating its use for Non-Hodgkin’s Lymphoma (NHL). Our population was quite small, as was the NHL population, primarily due to the small number of trials. ALCL is fairly rare in the overall population, and getting even a small percentage of patients who can travel to the trial center is difficult to say the least.

I traveled to Silver Springs, Maryland the day before our meeting and stayed in a hotel that smelled of mold and age. Usually when I travel to a new place, I try to get a feel for the city by walking around a bit, but I honestly just wanted to get to bed, get up and get to the meeting. I wasn’t anxious in any way, but I had a huge amount of curiosity. I also had no misconceptions about the potentially very small role I would play, but I was determined to speak up when I felt I should and not be intimidated.

The next morning, we were instructed to meet in the lobby at 7am where a transport bus would take us to the FDA White Oak Campus. We boarded the bus and made our perfunctory introductions to each other, at which time I became identified as ‘the patient rep.’ The others on the bus were all doctors/scientists and the talk was all about the Avastin meeting in weeks prior. Apparently there was quite a circus; protestors, massive amounts of press, women with advanced breast cancer, and caregivers in tears. To a person, none of them ever wanted to be in a meeting charged with as much emotion and controversy ever again.

We arrived at the campus, went through security, and were led into a fairly massive room with many rows of chairs for spectators, press, and patients who wanted to give their stories in support of the drug. The front of the room was in 3 sections: to the left were two rows of seats for the Seattle Genetics team presenting the drug to sit, (approximately 22 people, in all). To the right was a section of equal size for FDA staff. The largest section was the middle where a very large ‘U’ shaped table was constructed with the committee members for the meeting seated all along the outside. These members were physicians, scientists, FDA members, and me, the patient rep. There was a huge video screen behind the table for the presentation materials to be shown, although we all also had the printed materials in front of us.  The back of the room was sparsely populated with video camera set-ups for recording and webcasting.

Committee Room

Committee Room

All of the people on the committee were veterans of this process except me, so there was a lot of chatter between them as they made their greetings, but the proceedings were not discussed, and specific instructions not to discuss the proceedings were made clear.

I was greeted by several FDA people I had either met or was acquainted with through email and made to feel comfortable. My session was the second half of the day, so I got the benefit of watching the first proceedings, Adcetris for NHL, and getting educated on ‘how things work’ in these meetings. The room was 80% empty, so it felt very large and very quiet. Just as a note, this was a very well thought out presentation room with all the high tech gadgets, connections, cameras and speakers so any presentation materials could be seen and heard with ease and clarity even if the room were at capacity.

Going into this meeting, I confess I had definitely developed a strong opinion about what I thought about the drug we were evaluating. Based on the clinical evidence in the presentation, it seemed pretty clear what the verdict would be, but I quickly learned that there are two ways to look at the materials and statistics, and the scientists’ and FDA’s missions were to debunk whatever they could in the materials from Seattle Genetics. That is not to say they were completely adversarial, but they looked at the statistics in a different way and turned them on their heads so they didn’t seem to be as strong.

The meeting agenda was as follows:

Call to Order
Introduction of Committee

Wyndham Wilson, M.D., Ph.D.
Chairperson, ODAC

Conflict of Interest Statement

Caleb Briggs, Pharm.D.
Designated Federal Officer, ODAC

Industry Presentation
Brentuximab Vedotin
Systemic Anaplastic Large Cell
Lymphoma
Introduction

Seattle Genetics, Inc.
Elaine Waller, Pharm.D.

Senior Vice President, Regulatory Affairs
Seattle Genetics, Inc.

CD30 Directed Therapy

Barbara Pro, M.D.
Associate Professor
Fox Chase Cancer Center
Philadelphia, Pennsylvania

Treatment of Patients with
Systemic Anaplastic Large
Cell Lymphoma

Dana Kennedy, Pharm.D., BCOP
Medical Director
Seattle Genetics, Inc.

Safety Profile

Tom Reynolds, M.D., Ph.D.
Chief Medical Officer
Seattle Genetics, Inc.

Systemic Anaplastic Large Cell
Lymphoma Benefit:Risk Profile

Barbara Pro, M.D.

FDA Presentation

Karen McGinn, M.S.N., CRNP
Clinical Reviewer, Division of Hematology
Products, OODP, OND, CDER

All of the presentations by the Seattle Genetics and the FDA were extremely detailed and informative. I didn’t really find them lacking in information, but there was clearly a problem with the very small sample of patients that Seattle Genetics had for their trials.

After the full presentation, there is a time for clarifying questions from the committee; this is where things got a little bit contentious. Some of the panel members were clearly interested in showing their brains and some were intent on pointing out flaws and ‘schooling’ the presenters on things they did wrong. There were a lot of very detailed questions asked about the study, and comments were made about where the panel thought their methodology fell short of the mark. Statistics were disputed, although not outright challenged, and while there was a distinctly combative atmosphere, it began to emerge that the panel liked the possibility of this drug, but not some of the information-gathering techniques.

This was also where the subject of clinical trial size came up and was identified as a major problem when reviewing a drug for a rare disease, as ALCL is. In a nutshell, it is difficult to get the patient sample size you need to give statistics that are robust enough to give confidence that the drug has been tested enough to ensure safety and efficacy. Since this drug targets CD-30 expressing cells, this arose as the potential path for the future to get larger populations and also address other cancers that express CD-30.

After panel members completed their first round of exhaustive and comprehensive questioning, the public got its turn; Seattle Genetics had flown in two patients whose lives had been irrevocably changed by the use of the drug, and they both told heartrending tales of facing death and being given a new opportunity to live normal lives. The stories were very personal and very hard to ignore in the process of evaluation. A lot of tears were shed, as I am sure many have been shed in that room for many different committee meetings over the years.

Once this is all wrapped up, there is a last call for questions, then we got down to the purpose for the meeting with two questions:

  1. VOTE: The FDA has identified limitations of trial SG035-0004.   Should the FDA grant accelerated, regular, or non-approval for brentuximab vedotin in the treatment of patients with relapsed or refractory systemic ALCL?

Our choices for the answer to this question were:

  1. Accelerated Approval
  2. Regular Approval
  3. Non-Approval
  4. Abstain

If the answer was to grant accelerated approval, the second question was:

  1. DISCUSS: If the Agency were to grant accelerated approval for brentuximab vedotin, please discuss potential confirmatory trials.  Please discuss endpoints and comparators.

If accelerated approval were chosen, the presenter would be tasked with doing more confirmatory trials to get a stronger risk vs. benefit profile, which obviously costs millions of dollars, but they get to take the drug to market. They obviously would prefer the regular approval so they could fire up their marketing machine and get to market without further costs, but their trial size was just not big enough in the end.

In the end, the drug received accelerated approval for both NHL and ALCL, and the path forward will be approval for disease with CD-30 expression, which opens potential for treatment of other patients. The drug was seen as extremely promising, but Seattle Genetics now has a window of time in which they MUST complete a predetermined number of trials for further study and full approval at a later date.

Overall, I found this entire process to be very effective in coming to a solid, informed decision, but it is also very controversial by nature. There are always going to be people who are not happy, and sometimes that will result in millions and billions of dollars wasted and, in some cases, the shuttering of entire companies. The number of drugs that come before the FDA is staggering, and science is speeding up, not slowing down. As more and more therapies and devices are created, the task of thorough and effective review for each compound or device will become increasingly daunting to say the least.

The FDA is becoming much more transparent, and there is little information that the public cannot obtain by exploring the FDA’s excellent website to learn more about the agency, its internal processes, and its massive archive of drug information and internal processes.

I think there is an increasing need to fund the FDA more robustly, as this vital public agency’s needs continue to grow exponentially in order to keep pace with scientific developments. I hope that these critical needs can and will be met so that the future battleground in the fight against chronic and lethal disease as well as the strategies to ensure public safety are as effective as possible.

Be well,

Richard MacIntyre