Anita's Excellent Adventure: I Speak Before the FDA ODAC

During a clinical trial clinic visit in January, my trial coordinator at Roswell Park Cancer Institute asked me if I would be interested in speaking before the FDA’s Oncologic Drug Advisory Committee about my experience as a patient taking the experimental drug rociletinib. Clovis Oncology, the company that makes and is testing the drug, was hoping to receive accelerated approval to start being able to sell this drug on the market, and a hearing scheduled for Tuesday, April 12 before this important advisory committee was key. The company was looking for patients to speak about their experience with the drug. 

I immediately said yes. Such opportunities are rare, and it’s exciting to have an opportunity to be part of the important process of drug approval beyond taking a drug as an experimental subject. As a bonus, the hearing would be held in Silver Spring, MD, near where our daughter lives, and I would get to see her and her husband.

In February, I talked with an executive from Clovis, and he confirmed that the company would like me to speak, and would pay my travel costs. The following week I found out that my cancer had started to progress after two dose reductions of the trial drug, and I was no longer in the clinical trial. I immediately emailed my contact at Clovis, told him I’d been booted from the trial, and suggested that I might no longer be a good candidate to speak before the ODAC. I received a most gracious response back saying that they still wanted me to speak. To quote from the email, “If you are still up for it, it would be an honor and a privilege to have you speak to the Committee.” I was up for it.

A woman from an independent consulting firm contacted me to make arrangements. She arranged my flights and sent me a general outline of how these presentations are usually structured. This way Clovis did not know what I was going to say; my talk was not going to be reviewed or approved, and I was to speak candidly.

I didn’t fly first class, but this was a very comfortable trip. Clovis sponsored a dinner at the hotel where the other patients were staying with their families on Monday night, and we enjoyed meeting each other and sharing a delicious meal. Besides me, there were family members of a man who had died but who had five good months on the drug, an 84 year old man who had a nearly complete response, an army officer in his 40’s who had been diagnosed with stage 4 lung cancer while serving in Afghanistan, and Celia, a fellow blogger who I’ve been reading for many months. You can read her post about this experience at https://celpeggy.wordpress.com/2016/05/01/my-co-1686-speech-speech/. When I first found out about this opportunity for patients to speak about their experience, I thought to myself that Clovis really needed to have Celia speak to the ODAC, because she has been stable on rociletinib for more than 2 years, a remarkable run. And there she was!

Here’s a picture of me with Celia, my daughter Ana, and her husband Michael:

 

All of the patients and families, and a representative from Clovis on the far right. We came to speak from California, Oregon, Florida, New York, and Maryland.

The next morning there was a car at Ana and Michael’s apartment at 7:00 AM sharp to take us to the FDA headquarters at Silver Spring. The hearing wouldn’t start until 8:30, but our group needed all that time to get checked through security, which is as tight as at an airport, to sign in, and to find our seating section. Ana and Michael sat behind me. We would be speaking during the public comment period, and I drew number 4.

The hearing was very formal, with a uniformed designated federal officer and chairperson at the head table, members of the ODAC at two tables set up perpendicular to the head table, and a group of chairs for the drug company’s delegation to the left. A stand and microphone were set up near the designated row for open public hearing speakers. It was a big room with quite a few seats for the public and press to attend, and it was full, because there was a lot of interest in this particular hearing.

After opening statements, Clovis Oncology had 45 minutes to make its case. Using a powerpoint presentation, it presented data collected and analyzed from two phase 2 clinical trials, one of which was my trial. Clovis’ representatives discussed the pressing need for additional treatments for non-small cell lung cancer and rociletinib’s efficacy and safety. Dr. Ross Camidge, a leading clinical oncologist an researcher, discussed how the drug could make a positive difference in a clinical setting. The numbers all looked good to me as a lay person without the tools needed to analyze statistics on the fly.

Then the hearing was turned over to the FDA, who had 45 minutes to discuss their analysis of Clovis’ findings. They had a lot of concerns, especially about the drug’s safety and about the company’s proposal to increase the drug’s recommended dose by 25%. They were also concerned about the design of the phase 3 trial that is already in progress, saying that they doubted that the trial would prove one of the two objectives that the company wants to prove: what is the best dose of rociletinib.

The safety discussion was personally interesting to me, because the FDA is very concerned about the high incidence of QT interval prolongation observed during the trial. This is the side effect that ended up getting me booted from the trial  because I could not tolerate an effective dose of the drug (although the reason listed for me is probably disease progression). I was getting EKGs every three weeks, but once this drug is approved for clinical use, patients are unlikely to be so closely monitored. QT interval prolongation is silent, you do not feel it, and it can cause sudden death. I also learned why I had both hyperglycemia and QT prolongation. As rociletinib breaks down in the body, it produces two metabolites that are associated with these side effects. These metabolites are broken down by NAT2 acetylation. 40-60% of white and black people are slow NAT2 acetylators. The metabolites build up in the system for these people, resulting in side effects. I’ll bet you a dollar that I am a slow NAT2 acetylator.

After the FDA presentation, the hearing became a question and answer period, with members of the committee asking Clovis representatives for further explanations of their data. There were a lot of questions, and this section of the meeting ran over time. I’m afraid that the poor Clovis team must have been in a pool of sweat during and after this ordeal, as many of the questions were quite specific about aspects of the studies such as sample sizes.

My daughter the biostatistician was eating up this discussion. Later on she explained that many of the questions were probably based on statistical computations that committee members would be capable of making from the data presented. Her own back-of-the-envelope computation led her to think that the sample sizes in the phase 3 trial that is underway would be plenty big enough to prove efficacy compared to the standard of care treatments that rociletinib is being compared to, but not big enough to settle the question of best effective dose.

After the questions were done, we had a short break, then our group gave our statements, along with a doctor who spoke in favor of the drug and a representative from a public interest group who spoke against it. My nervousness transformed into nearly calm focus, and I spoke clearly. My statement was honest about my side effects, informative about how my medical team found a successful way to control hyperglycemia. and positive about my good quality of life and belief that patients and doctors need options due to the individuality of cancer.

After we spoke, the hearing switched gears, At this point, the FDA asked the committee members to make statements about their opinion as to benefit versus risk with this particular drug. The comments were cautious and concerned, and many of the speakers said that they were moved by our statements. Then the FDA asked the committee to vote on whether the FDA should wait until the phase 3 study was completed before approving rociletinib. The committee voted 12-1 in favor of the question. This was a very disappointing end to the hearing for Clovis Oncology. Drug approval may still happen, but not for more than two years in the future, as the phase 3 trial is not expected to conclude until 2018.

As we waited for our car, there was Dr. Ross Camidge on the sidewalk waiting with us. I went over and shook his hand, and thanked him for everything he is doing to advance the treatment of lung cancer. It was like meeting a rock star.

Our work was done, so I went home with Ana and Michael. After lunch, we went to the zoo. It was a pleasant sunny day, not too hot, and we were rewarded by seeing many animals out and about.

Moving otters are hard to photograph!

The lady lions were enjoying the vocalizations of a young male next door.

The next day, a car picked me up and took me to the airport, and my excellent adventure was nearly at an end. An hour later, I was in Syracuse, getting kisses from both my husband Robert and Samwise the labradoodle.

Thank you, Clovis Oncology, for giving me this opportunity to speak on the record about my experience with taking your experimental drug. Thank you for investing in the clinical trail that gave me eight months of good quality life. Your representatives were kind and supportive, and I wish you a path to success.

New adventures start up again, beginning tomorrow!

POSTSCRIPT:

Shortly after I wrote this blog post, Clovis Pharmaceuticals announced that they were ceasing development of rociletinib and closing all clinical trials. It is highly unlikely that this drug will ever be available for patients. I am still grateful for the opportunity to participate in this clinical trial, and believe that this drug extended my life. My experience with QT interval prolongation from rociletinib was, in the end, part of the very concerns that led to the recommendation for no FDA approval until successful completion of a phase III trial. For more information, see the following links:

http://www.fiercebiotech.com/biotech/fda-advisers-pile-clovis-rociletinib-turn-thumbs-down-fast-ok

http://www.onclive.com/web-exclusives/clovis-ends-development-of-rociletinib-in-lung-cancer