OR WAIT null SECS
Today's highest science, most fierce competition-and make no mistake, biggest gains-are coming from the oncology arena. In fact, there are more than 380 cancer compounds in development, according to a recent report by IMS Health, with almost 100 of them in Phase III trials.
Today's highest science, most fierce competition—and make no mistake, biggest gains—are coming from the oncology arena. In fact, there are more than 380 cancer compounds in development, according to a recent report by IMS Health, with almost 100 of them in Phase III trials.
The exciting news is that the investment in targeted therapies is paying off: Patients are living longer. But while these biologics are offering the very real benefit of extending survival, their price tag has made the payers restless. As a result, these incredibly efficacious—and expensive—drugs are jeopardizing the very way pharmaceutical companies commercialize cancer therapies.
What's emerging is a new set of rules for how to play to win in oncology. To offer insight and analysis in this area, Pharm Exec teamed up with Campbell Alliance to recruit Genentech's Bruce Seeley, Bristol-Myers Squibb's Robert LaCaze, and Pfizer's Alison Ayers for an executive roundtable. Together, these execs, and the companies they're from, represent the cutting edge in cancer care today. These front-runners say succeeding in today's oncology marketplace means not playing a game of selling, but rather starting in development to create cancer drugs with profiles that patients will demand. An edited transcript of their conversation, moderated by Pharm Exec Editor-in-Chief Patrick Clinton, follows:
PATRICK CLINTON: Today we are talking about how the oncology field has changed so we can make some predictions about the future. Let's start by looking back a decade: What was the oncology space like then?
LACAZE: There were only a few companies in this space. Bristol had most of the cytotoxins. You saw AstraZeneca with hormonal agents. And, obviously, Aventis had cytotoxins, Glaxo had Zofran [a drug that prevented chemotherapy-induced nausea], and some of the supportive therapies were just coming into play.
Bruce Seeley, senior director of Herceptin marketing, Genentech
AYERS: At that time, cancer treatment was really one size fits all—with the exception of breast cancer, where you had the hormone-responsive versus nonresponsive. It was very unsophisticated—no customization of treatment according to biomarkers or any prognostic factors. It was throwing cytotoxic drugs at the patient to the point of maximum tolerability and then backing off a little bit so that you killed the tumor before you killed the patient.
SEELEY: Back then, it was this smorgasbord of different types of cytotoxics, and there was a lot of experimentation. But, really, patients were being treated without a lot of guidance from clinical trials that showed bona fide, strong, conventional end points.
In today's regulatory environment, the type of clinical data that was available 10 years ago would have a very difficult time getting approved. For example, insurers were in many cases forced to pay for bone marrow transplants and other therapies without a whole lot of data to support those decisions.
NAEYMI-RAD: The average drug took around 500 days to get FDA approved, but oncology drugs only took 200—or less.
Many drugs were approved on Phase II data, and in some cases, single-arm studies. So companies did a few small trials, their drugs were approved quickly, and they went on the market without a lot of marketing investment—small number of sales reps, most of the focus was in medical affairs. You conducted a lot of post-marketing studies to examine where else your product could be used.
Ten years ago, oncology was kind of like the Wild West. Nowadays, it's quite the reverse. It's like that kid who wasn't popular in high school but now is at the reunion and everybody loves him, because he has matured and become more successful. Oncology is no longer the old dusty corner where you have to justify your existence. It's very much the place to be for a modern-day pharmaceutical—and especially biotech—company.
CLINTON: When did it begin to change?
AYERS: I think it is going to be changing rapidly in the future. In most tumors, the traditional cytotoxic regimen is still the gold standard—we are increasinly seeing targeted therapies added on.
NAEYMI-RAD: Historians may one day call this period the Early Renaissance in oncology. Never before has the development pipeline been so full of oncology products. These will inevitably impact the market five, 10 years down the road and have a profound impact on care. This is probably just the first chapter in what will be a drawn-out epic.
We're seeing a large number of $10-million-plus deals for products that are still in discovery. In oncology, between 2004 and 2005, there was somewhere in the region of 40 to 50 deals. In contrast, the next highest was in CNS at 20 or 25. Cardiovascular was at 10. So none of these therapeutic areas had as many deals so early in development.
Robert LaCaze, vice president, US oncology marketing, Bristol-Myers Squibb
CLINTON: That speaks to the competition for compounds in the pipeline. But what about the competition between products on the market?
SEELEY: When Taxotere came into a marketplace dominated by Taxol, it changed the equation of competition in oncology.
NAEYMI-RAD: The door policy for oncology has now become a lot tighter. It's become much more expensive and difficult to get into and, I would argue, much more difficult to sustain. A lot of companies have struggled to maintain their franchise's momentum in light of some of their key assets going off patent.
Now the pace at which products are coming out has gone up exponentially. Colorectal cancer is one of my favorite examples: More has happened over the last seven years, with the advent of Camptosar, Eloxatin, Erbitux, Avastin, and the other products that followed, than in the 20 years before.
AYERS: We have an overabundance of riches in the research pipeline right now. There are three angiogenesis inhibitors on the market, but there are 40 in clinical development. And at least nine of those are in Phase III trials for breast cancer and nearly as many for non-small-cell lung cancer.
We're getting to the point of oversaturation. Where previously almost every drug that made it onto the market had some niche, now we're going to have to differentiate oncology drugs like we do cholesterol-lowering agents. Choosing between them is going to be really difficult.
LACAZE: Efficacy is always going to be the key driver, but efficacy is going to be the entry. And safety and tolerability will also continue to be paramount. But drugs will increasingly compete on quality-of-life issues, especially as you move into maintenance therapies. We see that right now in several disease states.
CLINTON: Competition is bringing about many new challenges for marketers of cancer therapies. But it seems they are fighting over the smallest piece of the pie by targeting late-stage patients.
SEELEY: Investigators and companies are sometimes hesitant to move rapidly into the early-stage setting, not the least of significance because of long-term safety issues that may not have been identified.
The way Taxotere was approved on very early data, and in a fairly broad indication, is very different from the way drugs are getting approved today in very small niche indications—third-line, fourth-line, for example.
AYERS: Investigators insist that every patient has to have the current standard of care. And IRBs [Institutional Review Boards] insist on that too. So you have to add your drugs onto the current standard of care. And if we do that, we end up with these incredibly complex and expensive regimens.
Because regulatory authorities insist that we do development that way, and the investigators, quite rightly, don't want to be sued for not giving their patient the standard of care, it's almost like we've gotten stuck with having to do studies that arenreally advancing the science or showing the best way that these drugs should be used. It's very hard to see what we have to do to earn the right to start changing the standard of care instead of just adding onto it.
CLINTON: Drug development is oriented toward late-stage cancers, but the business opportunity is with early-stage cancers. Any ideas about how we get from where we are now to where we would like to be?
LACAZE: I'm not certain if anyone has the answer to that because, if we did, everybody would be doing it right now. But FDA is trying to work with companies, with the Critical Path Initiative, to help companies get through this. Otherwise, you just have to launch your product as a third-line therapy and gradually develop data and pursue approvals for earlier lines of therapy.
Alison Ayers, group leader, commercial head oncology worldwide marketing, Pfizer
AYERS: The first step is diagnostics. Obviously, with breast cancer we're doing a great job because we have widespread use of mammography, at least in the United States. But until we have the diagnostics that can identify through a genetic profile if somebody is predisposed to developing cancer, or until we have better imaging or blood tests perhaps, it's going to be really hard to pick up those early cancers.
Personally, I think that we're only a few years away from drugs that have the right profile to be used in early-stage patients, but the point is finding [the patients]. And, of course, it's important for governments to commit to screening because companies are not going to develop a diagnostic if the governments are not going to pay for screening.
CLINTON: Where are the opportunities today to use targeted therapies to treat cancer patients earlier?
SEELEY: Today, treating patients is much more prescriptive. Many oncologists treat their patients based on ASCO, NCCN, insurance-company guidelines, and their own internal guidelines.
NAEYMI-RAD: There are some populations, like the very elderly with co-morbid conditions, who simply cannot tolerate—even with the best supportive care—a cytotoxic regimen. Those patients are not always your average, first-line metastatic patients.
Now that there are a growing number of kinder, gentler biologics available, it is an area open to experimentation. Whereas physicians would not use an all-biologic therapy for first-line for most of their patients, for patients that just can't take chemotherapy, they may try it.
AYERS: Right now, the system is set up in such a way that you have to earn the right to move earlier. So you do your study in a salvage population to earn the right for it to be used in a first-line metastatic population.
Once you've established that, depending on your data, you may earn the confidence of investigators and patients to move into an adjuvant setting. And when we follow that paradigm, because we had to get five years' survival, we get our adjuvant indication just about the time when our patent is expiring.
CLINTON: It sounds like a good way for treatment to evolve—but not a good way to grow a business.
AYERS: Tamoxifen is a good example of that because it was trailblazing in terms of getting approvals—first in adjuvant treatment and then in DCIS [ductal carcinoma in situ], which is precancerous, and even to be used in place of mastectomy in women who are at high risk of developing breast cancer. Those approvals came about the same time the patent expired, so they never got any commercial value out of them. And that's the real problem that we have to change.
Nader Naeymi-Rad, senior vice president, brand management practice, Campbell Alliance
CLINTON: There's another big shift happening within the oncology arena: oral therapies. How have they changed the marketplace?
LACAZE: At Bristol, we've done some of the research around the dynamics in the infusion centers. Some patients say going to the infusion centers reminds them that they have cancer. They don't like it. When you talk with other patients, though, they actually find that very therapeutic from the standpoint that they can talk to other people experiencing the same issues.
So when we ask patients, oral versus intravenous, they overwhelmingly say the oral agents. But in the near future, probably in the midterm over the next decade or two, both IV and orals are going to play an incredibly important role in treating patients.
AYERS: The real issue is who pays for them—and right now, for many US patients, the oral anticancer drugs are on Tier III with a very high co-pay. Medicare patients taking oral drugs go into the doughnut hole and have to pick up a significant amount of costs, whereas if they get an IV drug, they don't have that issue.
It's really anomalous because oral treatments could cost less overall without the office visits for the IV administration. Then when we go outside of the United States, we have the same type of issues about moving from a hospital budget to a pharmacy or some other sort of primary care–type budget. And those budgets don't want to pay for oral drugs.
LACAZE: Three years ago, oral therapies weren't covered at all. So while this category isn't perfect, Medicare Part D at least makes it available to many patients who couldn't even attain it three years ago.
SEELEY: We will have to see whether the reimbursement system evolves to where the pharmacy budget and the IV budget merge and the trade-offs can be made between the full selection of therapy options—or whether they'll remain like they are now, in relatively separate budgets.
CLINTON: But for now, cancer patients on Medicare that use oral drugs hit the doughnut hole in March.
AYERS: That's an issue. I hope, going forward, Medicare would amend that so that for catastrophic care, patients weren't forced into that situation. That's too much of the burden that cancer patients should have to cope with.
CLINTON: Has Medicare changed the way physicians prescribe therapies?
SEELEY: It significantly reduced the buffer between [therapy choice and] reimbursement. It has made some physicians more anxious about the therapies they choose for particular patients—there is a risk that they might not get reimbursed for that particular therapy. And I think that has some impact on the way patients are treated today versus prior to MMA.
LACAZE: Especially as it relates to off-label or non-compendium areas.
SEELEY: We need to do whatever we can to promote enrollment in clinical trials, because that's the way we are going to get answers about off-label use. That's really going to be worth a lot more to payers and patients than anything else that we do.
CLINTON: Many companies have been drawn into the oncology field by the specter of very high prices—with payers willing to reimburse them. But that's not always the case today. How is the environment surrounding pricing changing?
SEELEY: More oral therapies coming down the pipeline has driven the need for industry to emphasize alternative payment methodologies like access, co-pay assistance, underinsured programs, and various other supports to tackle the financial need for oral therapies.
AYERS: In the case of the Pfizer drug Sutent, we haven't actually had payers who were refusing to pay for it. Instead, in the United Kingdom, the NICE Commission has been slow to complete its evaluation. They're postponing the review of the data. And until they come out with the health–economic analysis, no budgets are apportioned to it.
And the patients are beginning to protest. We've also seen NICE rejecting Tarceva, Avastin, and Altima because they consider anything that costs over £30,000 [sterling] per quality-adjusted life-year as not good use of National Health Service expenditures. They've put a cap on what they're willing to pay, and anything that's more than that, they don't consider cost effective.
The worrying thing is that there are now more European countries that are considering adopting that kind of health–economic cost-effectiveness approach. We just have to see how far that goes.
There's also much less willingness to pay for off-label use now. Going back to 10 years ago, it would have been very rare for anybody to challenge what an oncologist wanted to give to his patient if he believed the data was there. Now, there are a lot of countries that only will pay for a drug to be used within its strict-labeled indication, even if there is really good data about its activity.
CLINTON: How does the United States compare to Europe?
SEELEY: In the United States, we are not seeing the same sweeping NICE type of judgments regarding oncology reimbursement. But there is no doubt that the pricing of oncology drugs and the overall expense is a very big concern of payers. Now, they're paying much more attention to it, and they are hiring specialists who deal with oncology within their organizations.
NAEYMI-RAD: Europe is just so much more difficult. If we were to look at the United States, there is more choice in terms of payer coverage.
US payers are going to be very selective about where they focus in oncology, and they're going to look for worthwhile wins—which will be in the large-tumor types. They're probably going to look in areas where there is a lot of competition and choice, because that's how they can encourage cost savings.
CLINTON: What are the most important pricing issues for companies to keep their eye on?
SEELEY: Once your product is approved and on the market, drug development doesn't end there. In fact, it's really just beginning. Drugs are in a continual state of development in oncology, and yet we price at a single point in time.
Sometimes there are different doses, different schedules, that are developed—sometimes both—that can change the financial ramifications of a particular therapy. That makes it a challenge to set the initial price for a particular drug at a particular dose at a particular schedule. And you may not know it, but two years from that date of approval, you could have different schedules and different doses that could change the price of a therapy.
NAEYMI-RAD: What is difficult for payers is obviously advocacy pressure. I mean, people with cancer want the best choice available to them.
We are also interested in how payers could enact therapeutic caps. While this is still very much in a hypothetical form, you could see the day where a payer would say, for a first-line colorectal cancer patient, "For X dollars, you can get very good choice and very good care. Anything above that, you're going to need to get some kind of prior authorization to say why you need multiple branded products instead of generics and bio-similars."
CLINTON: All the new competition, the focus on reimbursement, the increasing specialization of therapies. How do you see sales reps fitting in with this new paradigm of cancer commercialization?
LACAZE: We have all these different drugs, all the different clinical trials, all the new data coming out; it becomes extremely difficult for physicians to keep up with the latest information. From a selling standpoint, the representatives provide a very valuable service—albeit sometimes the information they can disseminate is a lag to the label.
We have to get smarter and better at delivering information. We need to start acting more like others do in primary care– type selling where there's lots of different segmentations of the audience—both the physicians and the patients.
SEELEY: The job of the sales representative becomes much more difficult, because not only do they need to understand their product but all the other products that are being used in that particular patient. The level of knowledge that a sales representative has to have in order to bring value to the customer is very significant. Plus, I would argue that in a more competitive environment, sales reps also need to have much stronger fundamental consultative skills.
AYERS: Compared to 10 years ago, it's incredibly hard to disseminate new clinical data if it's not strictly within your label in every aspect of the patient populations studied. And that's a tremendous shame because we have sales representatives who are extremely well trained and capable of having discussions that can inform physicians about good data and peer-reviewed articles.
CLINTON: What other aspects of the commercial organization are also undergoing change?
NAEYMI-RAD: Medical affairs is where most of the service is provided to the customer in terms of addressing their questions and doing studies that provide useful answers to real-world problems. Although medical affairs is not commercial anymore, it needs to go to an entirely different level in terms of how they're going to serve the customer in a more restrictive environment because the marketers and the salespeople just can't go there.
SEELEY: There is no doubt that the legal and compliance environment has changed the way that pharma marketers and sales reps do their jobs. But we have seen these legal and compliance changes generate interest in areas that were underutilized in the past: e-marketing and the Internet, large investments in developing managed-care materials, access programs—making sure that your copay-assistance programs, your uninsured-patient programs, things like that, are the best that they can be.
CLINTON: People talk about, and hope that, the future of cancer care means treating patients like they have a chronic disease. Where are the early signs this is happening?
SEELEY: With the advent of new oral therapies, we're going to have to take some lessons from the primary-care arena. And largely, we already have. We're looking at pill burden, overall quality of life—even toxicities that previously wouldn't have been considered a big factor, such as diarrhea—things like drug–drug interactions, compliance in the elderly population. Marketers really need to evolve their thinking.
But when you're talking about chronic treatment of cancer, long-term tolerability is a key component. And I'm not sure we're necessarily there in terms of finding tolerable regimens that patients can take for years at a time. One early sign we see is Herceptin—FDA recently approved it in the adjuvant setting for early-stage HER2-poitive breast cancer patients.
CLINTON: Where are the areas of the biggest opportunity at the moment in cancer?
LACAZE: Pharmacogenomics. If you look at some of the pediatric cancers, it's not just about predicting efficacy, it's also about predicting toxicity as well. To get there is very difficult to do, but that is where the science is leading the industry.
AYERS: I personally hope that the opportunity is to make cancer look a lot like HIV—and that we are going to learn how to keep people alive. Some of them may be cured; others may need to take drugs for extended periods of time. But I hope that we can get smart enough to have a large armamentarium of different therapeutic options and to know how to combine and sequence them so that patients can really have extended survival.
NAEYMI-RAD: The biggest opportunity—and challenge—is for companies to be able to better predict the drugs their products will compete against tomorrow. Just the number of possible permutations on a set of regimens in any of the more crowded tumor types is mind-boggling. I mean, what [drugs] are you going to compare yourself with, knowing that that standard will almost certainly change by the time your drug gets to launch?
LACAZE: As a country, we're not where we need to be in the war on cancer. But if you look back to when the US declared a war on cancer in the mid-1970s, taking all cancers together, there was maybe a 50 percent survival rate. And if you look at the latest data, from 1996 to 2002, it's about 66 percent—a 30 percent increase in overall survival rates. That's because of better diagnosis, prevention, drug therapies, radiation, and surgeries.
We have a lot of new tools from a pharmaceutical perspective coming down, and what we're dealing with is how to incorporate all of this together and grow that number from 66 percent to 75, 80 percent—or as close as you can get to cure rates or chronic disease.