FDA committee votes no to Tivozanib

Many of you in the kidney cancer community have probably followed the development of Tivozanib, a new kidney cancer drug that the company AVEO is trying to bring to market. The FDA held a hearing comprised of medical specialists – mostly oncologists but, strangely, not kidney cancer specialists – to hear the case for Tivo.

The hearing did not go well. Dena and I were in attendance, as we were guest speakers, and both of us felt that most of the members of the FDA advisory committee had made up their minds before ever entering the room. The questions posed to the AVEO representatives were largely skeptical and even hostile. The 13-1 vote pretty much speaks for itself. It went something like this:

Doc 1: No

Doc 2: No

Doc 3: No

Doc 4: No

Doc 5: No

Doc 6: No

Doc 7: No

Doc 8: No

Patient Representative: Um, yes please?

Doc 9: No

Doc 10: No

Doc 11: No

Doc 12: No

Dena is working on a piece about how we think the logic that prevailed at the meeting was flawed, so I won’t step on her toes with any more commentary here. However, for those of you who have an interest in this drug, below is the testimony Dena and I gave at the hearing. I tried to approach it from the perspective of a patient while Dena gathered stories from friends in the kidney cancer community we’ve met over the years:

CHRIS’S TESTIMONY:

My name is Chris Battle. I come here today not as a representative with any official organization. I come today as a husband and father of two little girls that I would like to see grow older. I come today as a patient of kidney cancer urging you to approve the kidney cancer drug Tivozanib

In 2009 I was diagnosed with Clear Cell Renal Cell Carcinoma. The disease is metastatic, primarily in my lungs. Since my diagnosis I have undergone kidney and lung surgery. I have also undergone a broad variety of systemic treatments that includes:

• IL-2
• MDX-1106
• Sutent
• IL-15
• Inlyta
• Afinitor
• Votrient

All of these drugs are good drugs. They have done wonders for untold numbers of patients. Unfortunately, they did not work for me personally. And that is why I’m here today. To urge you to keep an open mind to the development of new drugs that could help people like me.

One key area of kidney cancer research for TKI drugs is sequencing. Oncologists don’t really know why one drug works for one particular patient but not with another. Some patients, for example, have gone on Sutent as their first therapy and it has proven a lifesaver. Others have gone on the drug and it failed to make a dent; they found themselves almost immediately looking for another therapy. They try another similar drug, say Inlyta or Votrient, and they do get a response. Why is that? We have no credible answers.

I was one of those people for whom Sutent did not work. In fact I went through that long list of drugs I just mentioned because none of them had any kind of sustained response for me.

There is also the matter of side effects. Some patients go on a drug and it appears to be working, but the side effects are so bad that they can’t continue. They try another drug and, for some reason, it’s more tolerable. Why is that? Again, there are no credible answers.

For me, it took the 8th drug – Cabozantinib — before I found one that worked. While I’m grateful for this drug, the process of finding it was fairly arbitrary.

In other words, many of these drugs seem very similar. This prompts a reasonable question of whether more are needed. But for the patient these drugs are not similar. That is, the FDA may look at the chemistry and clinical data of the drugs and see similar things; the patient, meanwhile, looks at the efficacy of the drug personally — and sees simply that one works but another doesn’t. All the data in the world doesn’t change that crucial fact.

None of these drugs works forever. I have studied clinical trials, waiting hopefully that another drug will come to market in case Cabo stops working for me. I’m running out of options. I’ve watched Tivo throughout its development in clinical trials. My hope that it will be there for me should Cabo fail.

Someday, perhaps, medical researchers will discover the key to sequencing these drugs, or develop biomarkers that indicate which drug will work for which patient. But for now, that discovery lies in the future. Patients like me can only hope that we have multiple options on the table. That is why I think you should approve Tivo. Thank you for your time today.

DENA’S TESTIMONY:

My name is Dena Battle.  For the past four years, my husband has been battling stage-four kidney cancer and I have been his primary caregiver.  Shortly after Chris’s diagnosis, we became actively involved with an on-line patient community called Kidney-Onc.  We also write our own blog called the kidney cancer chronicles.  Between the two groups, we’re in regular contact with close to 2,000 fellow patients.  Many of us have been following tivozanib throughout the clinical trial process and are excited about the possibility of having access to the drug.

What stands out about tivozanib for many of us is easier side effect profile – which improves both quality of life, but also allows for patients to stay on the drug for longer periods of time and at higher doses.

• One fellow patient who is currently on the drug Votrient, struggled so much with the drug, that he invested thousands of dollars in a high tech Japanese toilet.  I only have four minutes, so I won’t bore you with the details, but I think you understand the nature of his discomfort.  When he attempted to dose reduce, his tumors grew.  A drug like TIVO could give Mike significantly improved quality of life with prolonged tumor stabilization.
• Another fellow patient has had his extensive disease burden controlled for 6 years by Sutent.  But now the side effects are so significant that Shaun rarely plans activities outside the home during his treatment cycle.

For many patients, having a drug like tivozanib is a new lifeline because they can’t tolerate other drugs due to co-morbidities.  For example:

• A recently diagnosed patient reached out to us through our blog.  In addition to having stage 4 RCC, he suffers from Crohn’s disease.  His oncologist is reluctant to put him on other drugs due to severe stomach side effects, so he’s extremely limited in his options.  However, Tivozanib could very well be a drug that he could tolerate.  For a patient like Tom, this drug could be the one possibility he has at access to VEGF treatment.
• Another fellow patient suffers from an auto-immune disease, which also means that his treatment options are limited and he’s ineligible for clinical trials.  He responded well to Sutent, but now is having severe difficulty with Inlyta.  So much so that he hasn’t been able to titrate up to an optimal dose.  Given Tivozanib’s superior profile, it’s a drug that he should have access to in his arsenal.
• Another patient, a 5 ½ year survivor, suffered cardiotoxicity on Sutent with his heart function dropping to half of normal.  Within a few weeks on Votrient he developed Grade ¾ liver toxicity.  He is still active and healthy-but he’d welcome a less toxic choice when his next drug is needed.

Many of us hope that the lower frequency of serious side effects will mean that TIVO is combinable with other agents.  For patients with rare and aggressive subtypes like sarcomatoid – a VEGF inhibitor that is favorable for combination with chemo-therapeutic drugs could give these patients access to lifesaving treatments that aren’t possible right now.

Over the past ten years, we’ve seen explosive growth in kidney cancer treatment options – going from one FDA approved treatment to seven.  But, the reality remains that this cancer is an orphan disease that doesn’t receive the same level of funding, treatment or attention as other cancers.  It’s also a notoriously unpredictable cancer – with late recurrences, aggressive tumor changes, and erratic patterns of growth.  What works for one patient, often won’t work for another – and that’s why I’m here today to urge you to approve this drug.

As patients and caregivers, we need more tools in our toolbox – tivozanib is a tool we can use.

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