After a decade of near-absence from the US market, the AstraZeneca drug Iressa (gefitinib) is back.
The drug, which stayed on the market between 2003 and 2005, when it was pulled because clinical trials in a general population of patients failed to demonstrate a survival advantage, has returned. Now it is accompanied by a diagnostic tests that selects patients.
The Cancer Letter asked Andrew Coop, vice president, US medical affairs, oncology, at AstraZeneca to discuss the company’s plans for the future of Iressa in the US, and lessons that have been learned.
Coop spoke with Paul Goldberg, editor and publisher of The Cancer Letter.
Iressa was approved for patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.
The drug is approved concurrently with the therascreen EGFR RGQ PCR Kit as a companion diagnostic, which is sponsored by QIAGEN N.V.
Paul Goldberg: First of all, congratulations on bringing back Iressa.
Andrew Coop: Thank you. We’re thrilled.
PG: I was there, at the original ODAC, in 2002, when a large number of patients showed up to demand that the drug be approved. How has the state of oncology changed since that initial approval?
AC: I think things have evolved, and have continued to evolve a lot in those last years.
Again, you know the history of Iressa—but within that time, as we think about the initial approval of Iressa, at that time it was in an unselected patient population. We’ve really spent a lot of time in the past years trying to understand the science, the molecular biology, the targets and the response.
And so that’s something that AstraZeneca has certainly been very committed to—for over 20 years, for example, in this case. But broadly referring to your question as well as what’s changed in oncology, is I think you’ll see an absolute plethora; more and more of the desire to really understand the science of what’s going on behind the tumors, which patients respond, and why. There have been more and more drugs—and you’ll see this in AstraZeneca’s portfolio—being developed with a diagnostic in mind.
So this idea of targeting the right drugs to the right patient and trying to understand what’s going on in the tumor—and going back to what you said, there at the original ODAC—and where it’s come from, I just think there’s been a huge depth of understanding, certainly within AstraZeneca, but also in the work we do with the external research community.
Everyone is coming together to really understand these devastating diseases; these areas of high unmet medical need, and to have a thoughtful approach of how to target cancer. That, to me, is what I think has been my observation of the last few years.
PG: Let me share an anecdote with you: an ODAC member at that time said to me, “first I was going to vote no, then I was going to vote yes; then no…” Ultimately he voted yes, but he said that had it gone on another 30 minutes, he would have voted no. It was a fascinating time—it feels like the Dark Ages in some ways.
AC: I think what we’re seeing is the acceleration of science.
What can science do for patients, how can we put our best minds forward, both inside and outside, with industry and academia, working with patients, with advocates. How do we work to understand the disease, and then finding out what are the smart solutions.
PG: How has the science changed since the time when the drug was placed in restricted access?
AC: When the drug first came out—again, at that time it was in an unselected patient population, before it was known that EGFR mutation was the target for Iressa, and where to actually find that benefit and which group of patients had the best response.
As it went through that time when we stopped commercializing—for those patients who were still benefiting, we provided access to those patients. In R&D, the research continued.
We continued to follow the science, see what we could further understand, and really, based on that, is where we’ve landed today.
What’s happened in those last years is—obviously we had the IFUM study, which was the follow-up measure which was exploring the efficacy and safety in first-line, again in a specific population with patients with non-small cell with EGFR exon 19 deletions or the exon 21 substitutions, and that was a targeted trial as a follow-up measure.
We also did the exploratory analysis in the IPASS pan-Asian study as well. Really furthering studies and working to confirm that benefit in those patients harboring the EGFR mutation and also exploring other data sets. There has been a real commitment to follow this science and understanding over the last years.
PG: Are there still patients living who have been receiving Iressa since it went into restricted access?
AC: There are patients that are continuing. We do have a program for those patients. That program is now closed for enrollment.
But there have been patients treated, as part of our commitment to make sure those patients that are still benefiting from treatment, to make sure that they have access.
PG: Do we know whether Iressa responders are basically the same people as the Tarceva responders? Are these different cohorts, are these drugs interchangeable?
AC: We don’t have those head-to-head trials. Such a comparison isn’t something that we speculate on. But we are continuing to understand this.
In answer to your first half of the question, they have slightly different labels; different populations. They are different drugs. We don’t have the head-to-head data. But we are ready to explore that space.
PG: Is anyone actually doing a clinical trial, or is this a basic science question at this point?
AC: There are trials going on. If you go on clinicaltrials.gov, you’ll see the research. But I think in general there’s a lot of interest in these kind of questions around targeted treatments, per se, not just these agents, but also therapies in this space as well. I think it’s fair to say that there is general interest in people really trying to understand the biology of this disease.
PG: Who do you think should get Iressa now? I guess it’s a label question now.
AC: It is a label question, and I think it’s an important one.
Again, we have a label that gives specific guidance on the population who would be eligible to receive Iressa. And we spent a lot of time on that evidence generation and with the agencies around the world to provide that information and to help inform healthcare providers. It is also important to give information about mutational status, but also using the FDA approved companion diagnostic, which is also very important when people are thinking about prescribing this drug.
PG: Maybe I’m missing something hugely important, and I’m probably not alone, but I was actually fascinated to look at that page on the FDA website about approved companion diagnostics. It was interesting, because the Tarceva companion diagnostic is different from yours. Is that significant? It’s still EGFR.
AC: I can’t really talk to another drug or its companion diagnostic, but we’ve certainly worked with regulators and our companion diagnostic to make sure that people have a way of looking at this drug in combination with the diagnostic, so they can make informed treatment choices for their patients. Again, it goes back to what we said before about looking at the datasets, or where we’re comparing one data set to another.
PG: It’s just a fascinating question, because there’s EGFR testing going on that is called EGFR testing but each test is different.
AC: That’s why, within our label, we are talking about looking at positive testing on these deletions or substitute mutations as approved by an FDA-approved companion diagnostic test.
It speaks again to the robustness of the clinical data as we make these recommendations on our drugs. And it certainly is, as we look at our portfolio, something that we’re spending time looking at, and trying to bring them into our portfolio as we develop drugs with an understanding of the molecular biology.
PG: How much market exclusivity can you count on at this point?
AC: What I can say is what our commitment to is, we see a big unmet need in lung cancer here.
We’re happy to work with the FDA and bring it back, because we see an unmet medical need in this group of patients with lung cancer, and we’re also continuing our programs and research in coordination with other agencies as well.
From a medical side, looking at the needs and research, this is something that began for AstraZeneca in lung cancer—and we see a high unmet medical need and an opportunity to bring it forth, and in the future look at other combinations within our portfolio in that lung cancer space, where unfortunately the medical need remains very, very high.
PG: It’s likely that through combinations you could end up with more exclusivity?
AC: I think that—not talking about exclusivity or that component—what I’m saying specifically is that we’re committed to understanding the science. We have a responsibility to look at our portfolio with aims to improve patient outcomes.
PG: The drug is on the market now. One can actually receive it, purchase it?
AC: The drug is FDA-approved.
PG: Can you tell me anything about pricing? How does that work?
AC: What I can say is that we take that commitment very seriously and it’s comparative to other TKIs.
PG: So it’s in that same range. Is there anything we’ve missed? Anything you’d like to add?
AC: Yes, I think you touched on it, I think that this is a long heritage story for AstraZeneca. It started over 20 years ago, with this science with people looking at Iressa at that stage as a compound—and the consistent looking at the science, of working with regulators, of understanding the science, working externally to identify the groups of patients who can potentially benefit.
It speaks to what you mentioned earlier about looking at what’s the best way to look at these agents; to bring them forward. We have a deep, deep understanding of the science and now can bring it back into the United States, having been there at the beginning. We’re just very happy to be able to do this, given the high unmet medical need for these patients.
PG: When I think about it, I think of humility as a lesson here, because here’s this drug that was really the first EGFR drug, and it seemed that science understood what was going on, and yet it did not. It took so long for it catch up. Kind of an uplifting story, in some strange ways.
AC: At that time we didn’t know, but rather than shying away and not finding out—there had been signals of activity, it really was a case of going back and following that and understanding it more.
It’s this pursuit of understanding the science, of what we’ve seen and why. And I think that, to us, is the story; our commitment to those patients who were still benefitting, to continue to provide access to those patients in the United States, while we continued to figure out the science and a regulatory path forward.
PG: Congratulations again.