WebMD's Chief Medical Officer, John Whyte, MD, speaks with Alexander Hardy, Chief Executive Officer, Genentech, about the impact COVID-19 has had on pharmaceutical partnerships, clinical trials, disparities, and misinformation, all of which he sees as silver linings of the pandemic.
John Whyte: Partnerships, regulatory flexibility, virtual care, speed of innovation, diversity, and inclusion. These were not concepts or even buzzwords that typically were associated with the pharmaceutical industry just a couple years ago, but the COVID pandemic has changed the way we develop drugs, and many like my guest today believe the process has changed permanently and it's all for the better.
I had the opportunity to sit down with Alexander Hardy, the chief executive officer of Genentech. We had a wide-ranging conversation about the impact of COVID, the renewed focus on accountability to ensure diversity in clinical trials, the urgent need to combat misinformation. One thing you'll notice is that he kept coming back to what he sees as the silver linings of the COVID pandemic.
Alexander, thanks for joining me.
Alexander Hardy: It's a pleasure, John. Thanks very much for the conversation.
John Whyte: I want to start off with the impact of the COVID-19 pandemic on drug development, and you have consistently talked about the need for partnerships, and that's one of the things that you've learned and you've partnered with Regeneron on monoclonal antibodies, you've partnered with Gilead Sciences on treatments for COVID pneumonia in hospitalized patients. That's not the normal thinking for the pharmaceutical industry, this idea of partnerships. How did you come to that sense of need for partnerships?
Alexander Hardy: Well, I think it's one of the silver linings coming out of the pandemic, is the growing understanding of, of the impact that we can ... greater impact we can have as a result of partnerships and, you know, the, the examples you're, you're talking are private partnerships, but there's also public/private partnerships.
And, you know, our partnerships with the FDA and with BARDA, for example, have been very, very important as well. But I think, you know, we, we were all really challenged by the, the threat of the pandemic to, to our world.
And that's what galvanized us into, into action.
John Whyte: But isn't the pharmaceutical industry inherently competitive, right? So, here you're trying to compete against others, and you're saying, "No, we've got to work together to address this."
Alexander Hardy: Absolutely. I mean, you know, the, the ... We're all aligned around the enormity of the threat, and I think that was the ... The call to action was what changed mindsets. And the, the need for speed. So, you know, we're constantly partnering. We, we do a lot of particularly early-stage partnerships.
And those will continue to be very important, but those will often take months and sometimes years to, to make those partnerships happen.
And these partnerships happened literally in, in weeks.
And, and, you know, I think that's, those are the sorts of things that we want to carry on out of the pandemic, and, and, and the partnerships were, as you said, with, with companies that we are actually fierce competitors with and will continue to be fierce competitors.
Because that's a, that's very, very positive in terms of motivating progress and, and, and, and pushing the frontiers. Um, that's great, but I think partnerships are here to stay, and I, I think that's really exciting.
John Whyte: Yeah. Well, let's talk more about these public/private partnerships. You mentioned the FDA, a regulatory agency. What do you say to folks who will suggest that there should be this inherent tension between regulators and industry? What's your thoughts around that, that there, you know, can't truly be partnerships, because they have to decide at the end of the day with no vested interest whether or not they're gonna allow a drug to market? Is that change in thinking that's gonna persist?
Alexander Hardy: You know, I, I think this is a really a really interesting topic. So I see no change and I believe in no change in terms of high regulatory standards. They should maintain those, and they are maintaining those in the highest rigor. But I think the, the opportunity for dialogue, uh, the opportunity for fast and frequent conversations and consideration of doing things differently, because the science is moving so fast outside the pandemic.
And then inside the pandemic, you know, obviously there were frequent times where we needed a fast decision because things were changing.
John Whyte: Has COVID changed clinical trials permanently?
Alexander Hardy: I think COVID has certainly changed clinical trials permanently. We've already talked about the, the speed.
And how clinical trials are done. I think the other aspect which I, I think is another silver lining is we've seen, you know, the, the tremendous negative impact of, of COVID on underserved populations.
You know, we've, we've... It was always there, but now we've seen it in, in starkness.
John Whyte: I'm gonna turn to that.
Alexander Hardy: Yeah.
John Whyte: (Laughs) I have some, some tough questions. As you know, minority populations have represented the very small percentage of clinical trial participants, in the single digits, that, as you point out, COVID has shined a light on these disparities that honestly have persisted for decades. And, and now a broader population is recognizing that. Genentech has done several surveys in 2020, in 2021, including health care practitioners, in terms of trying to understand the impact of disparities and what we need to be doing. Can you talk a little bit about what your studies found?
Alexander Hardy: Well, the, the studies are very concerning. They show that, that people who are medically disadvantaged don't trust the health care system. Fifty percent of them don't trust the health care system.
John Whyte: Half.
Alexander Hardy: Yep.
John Whyte: Half. Yep.
Alexander Hardy: And that actually results in them, you know, what is the outcome of that? That results in them not doing the checkups and the preventative medicine. Taking their medicine, getting vaccinated. So it has real, it has real outcomes. And, again, we've seen those real outcomes in the pandemic. Really quite, really quite alarming, and very, very stark. We also see the issue of, of misinformation. You know, 80% of providers believe that misinformation is impacting specifically, disproportionately, the medically disadvantaged population. So, we already know that misinformation around science and, and medicine is an issue. It's a disproportionate impact on those medically disenfranchised.
So, it's another call to action for us to solve. So, the, the survey data, unfortunately, is not getting better. It's getting worse.And it's, it's a further call to action, and, and, and there is responsibility of, of companies like Genentech to, to lean in here and be part of, of, of changing this. Uh, I mean …
John Whyte: So what is your commitment? And I'm gonna push on you if I may a little.
Alexander Hardy: Please do.
John Whyte: You have a great line on your site from your medical affairs group, that it says investigators need to be intentional about recruiting diverse populations. But if you think about it, people are incentivized to be first, right? You want to be first to market, so you enroll who comes in the door, and minority populations are not typically coming into the door, even though these trials are being conducted in very ethnically and geographically diverse centers. So how is Genentech going to address that? You want to be intentional in recruitment, and you've done that in the setting of COVID, in terms of trials, but how do we do that in a post-COVID world?
Alexander Hardy: Well, you know, you know, this is, this is an area where I don't just want to talk about it. It's about action. And, and we were actually already taking action prior to COVID. This was already an area of focus for us. But, but actually we did things in COVID that have further proven, you know, what can be done here.
And, and, you know, let's unpack this, because, you know, it, it is often said, OK, speed is important.
And clearly speed is, is important, but, you know, if we, if we are trying to, to make sure that the studies are represents of the U.S. population, is that gonna be at the expense of speed? I don't believe it is, and I think we've shown that during COVID. Actually, the fastest study that we've ever set up, recruited, and moved to data analytics to, to final study report was in COVID and focused on, on underrepresented population, which was the IMPACTOR study.
85% of the population we recruited – it was a phase III study – were in underserved communities. The largest recruitment site was right on the, the edge of the Navajo nation.
John Whyte: But you do that from the very beginning, that point about being intentional. Some of your colleagues will say we do this post-market, right? We do it almost in a, in a phase IV. That's where we can look at it, because we need to get the drug available to people. Are, but are we gonna flip that around to some degree, as you're pointing out? We're gonna focus on getting them involved early on?
Alexander Hardy: Absolutely. We have a commitment that every single molecule team has to do a look at their, their clinical trial program with an inclusive lens. They're held accountable for doing that. And then, you know, to turn it into, to specific action to help them we have a, for example, we set up an inclusive research site alliance of, of sites that we're helping get up to speed where they have access to these populations.
And then we can, we can just put the studies into those sites. This is in oncology, so these, these sites are around the country in, in areas with, with underserved populations. We have an ongoing relationship with those sites, and we have a huge oncology portfolio. And we can then, those molecule teams can just go to those sites all the way through from phase I through to phase III, and they're ready to go.
John Whyte: But how do we hold, then, people accountable, as you say? Because when we look at the field of oncology, typically African-Americans represent 3% of clinical trial participants, and, as you know, many cancer trials are conducted outside …
Alexander Hardy: Absolutely.
John Whyte: ... of the world. So it's a different prism and what we're seeing of what defines diversity. But how are we gonna hold people accountable? There's been multiple examples, including breast cancer, where we're talking single digit numbers of African American women, not just percentage, but numbers of participants. And we don't know what the right number is in some ways.
Especially in diseases where it, you know, is small percentages. But you just look at that and you say, hmm, that, that can't be right. Not that there needs to be proportionality, but there needs to be representation.
Alexander Hardy: It isn't right. And, and it hasn't been right. And you should, you should hold us accountable. And we're prepared to be held accountable. For now and in the future, you know, are our studies representative of not only the American society, but specifically, let, let's go down to a particular tumor type. Let's say triple-negative breast cancer …
John Whyte: Exactly, yes.
Alexander Hardy: … which is obviously one which is disproportionately impactful to underserved populations in the United States. You know, are our studies mirroring that, that disease incidence and prevalence?
John Whyte: Historically, no.
Alexander Hardy: And historically, no. But you know, as I am explaining to you, we, we, we now have that lens. We're now very transparent, and we have a mechanism. And there's lots of, there's lots of other things.
And, you know, we're, we're, we're very keen to talk about these things, because we, we only – we don't want to just change Genentech. We actually want to change the industry and the whole medical environment in this space. So, you know, our ambitions are beyond just Genentech here. This, this needs to change at large.
John Whyte: Should we pay participants in clinical trials, particularly phase II and phase III? There's been a lot of discussion about that, particularly in the last 18 months. Not just from an issue of inclusion, but an issue of equity. These participants are giving us a great deal. Everyone else is benefiting from it. Academia, the clinical research organizations, you know, industry. Should they get paid to participate? That could increase the number of participants.
Alexander Hardy: I think we should consider this. And, and I'll tell you why, and, and it's, you know, it, you know, that's part of the reason why, you know, only 5% of the American population is involved in clinical studies in oncology is because, you know, it, it asks a lot of the patient to, to travel in frequently to a center, to, to go through all the treatment and the tests involved and the, the screening and so on and so forth. And we're missing out on 95% of the, of the populations with, with cancer data. And, and as, as the science becomes increasingly personalized, we're just, we're actually missing a big scientific opportunity to learn from that.
But there's also – and I think you raised a really good point – here's also an equity lens there.
That, you know, who are the people that can afford to take the time off to travel, to be part of a phase II, phase III studies. We're not reaching the underserved communities when we don't have these sorts of compensation.
John Whyte: Because historically – correct? – folks have not supported the idea. The fear of paternalism, undue influence, and inducements. But we know, particularly in cancer, if you fail standard therapy, if you don't enroll in a clinical trial, you have very limited options.
Alexander Hardy: You know, I think, you know, that some of the things we're gonna have to deal with are the topics you talked about. So there needs to be a discussion here around these things, because it's, it's, it's not simple. And there needs to be a, a discussion of what are the unintended consequences here or what could be the potential conflicts of interest involved. But there needs to be a discussion because the status quo is not satisfactory. And, again, you know, where the science is going, my, my concern is, you know, we've talked about some of the opportunistic parts of, of the, of where the science is going, and, and the COVID impact in terms of speed and partnership, but my concern is that the science could be heading in a way that actually perpetuates or even worsens disparity of access. So, for example, you know, as we're doing more and more science discovery and treatments that are focused on particular subpopulations with genetic characteristics of their cancer, you know, do we have that data? Do we really understand that data for our populations in the United States? Are we developing the drugs to produce the evidence which then will translate through to access for those populations? That answer is, no, we're not, and we need to do a better job. And there needs to be a whole bunch of different things that happen.
John Whyte: Sure.
Alexander Hardy: And you, you talk about the, the, I, I think the role of the investigator is critical. As a sponsor of clinical studies, you know, we have to ask for diversity. We have to build that into the contract.
John Whyte: You have to demand people.
Alexander Hardy: Exactly. Demand it. We have to work in partnership with the sites to recruit.
John Whyte: Back to partnerships (laughs), yes.
Alexander Hardy: Exactly.
John Whyte: Absolutely.
Alexander Hardy: To recruit the, the patients to make sure there's awareness, there's trust in those communities. This is what clinical studies are. Consent process, make sure that's really clear, transparent, and understandable. Building trust entirely all the way through. Investigators need to be representative.
John Whyte: And I want to point out, because you have a great section on your site that's actually called advanced knowledge of clinical outcomes across race, ethnicity, and gender, and it's exactly to your point. To phrase it another way, it's this variability of drug response. That people might respond differently to drugs based on certain characteristics. But if we don't study it, we're not gonna learn that. How did we come to this thinking over the past 18 months? Or am I being too tough? It was evolving to that point anyway, in terms of this representation in clinical trials?
Alexander Hardy: I, I, I think this was evolving, but like everything else in our world, it's been accelerated and the pandemic's had a role in accelerating it. There's also been, of course, the, the broader increase in, increase in awareness around social justice and inequity in our society and an awareness of the inequities. So I think these things are all working together.
And, you know, I see tremendous movement and, and, and commitment. I hear it constantly from the, the medical societies, from providers, from payers. I mean, we're, we're all, you know, lined up around this issue and, and making a difference. I mean, you know, as a company we have, we feel, you know, it's not just our role to advance science. The science is, is fantastic, but unless it gets ultimately to the patients that need it, and if we're talking about improving outcomes in a particular disease, which is our, is our passion, to, to, to push advances in, in, in, in outcomes and, and, increase survival in, say, lung cancer, you have to do that, not just improving outcomes in terms of this molecule, but equity is also how you're gonna do that.
We, we have a, we have a, a vision in, in the pharma division to, to increase the medical impact, the patient benefit, by three to five times in the next 10 years at half the cost to society. You know, part of that is increasing the output from our, from our labs with better molecules.
But it's also topics like personalizing care, making sure that the drug goes to the specific person that's gonna benefit from it. It's about topics like health equity, making sure that everybody has access, which is a complicated, long-term issue.
But that's how we're gonna get to three to five times patient benefit compared to what we're delivering right now at half the cost to society.
John Whyte: Absolutely. And, and let's talk about the future and as well as leadership during the pandemic. And, and as you know, we're interviewing several CEOs such as yourself to talk about how the pandemic has impacted leadership. And I want to start off with asking you, how has your leadership style changed, if at all, during the pandemic?
Alexander Hardy: You know, my, my leadership style was, was very much about empowerment and enabling. Making sure that decisions are pushed down the organization. Deeply, deeply listening to the experts.
We have so many technical experts at a company like, a company like Genentech in all their different fields. What the, the pandemic has done is sort of heightened the need for that, for us to, to move at the speed of the, the pandemic. It's actually accentuated the, the need for those things.
John Whyte: This is a beautiful campus that we're at. You can't go around (laughs) as much talking to people.
Alexander Hardy: Exactly, exactly.
John Whyte: You can't just, you know, meet with folks as easily, can you?
Alexander Hardy: Yeah.
John Whyte: Has, has it had to change the way that you engage with folks, or have you, like many others, have you just pivoted and marched forward?
Alexander Hardy: No, it, it's fundamentally changed, you're right. I do miss the, the ability to, to bump into people as I walk around the campus and hear what they're, they're working on and what do they need from us. Again, that's that's my style of leadership. What, what do you need? What's standing in your way?
One of the things, for example, that we've done, and, again, I think this is, this is, this is a silver lining, we're gonna continue to do this after the pandemic is, you know, every couple of weeks during the height of the pandemic we, we had an all company virtual – we called it the Genentech executive committee office hours where we would, for, for 90 minutes, it would be the executive team with all the employees dialing in, and we would have live questions.
John Whyte: OK.
Alexander Hardy: In a, in a large organization, I mean, this shortened the distance between the leadership team and the organization. We could see and hear exactly what was on the minds of, of people.
John Whyte: Well, let's talk about what's on the horizon for a few minutes. Alzheimer's disease is an area you're working on. That has undergone some controversy with some other areas of drug development. Recently there's been talk of a trial relating to vaccines for Alzheimer's. Lots of research going on. What's your prediction on where we'll be in the treatment of Alzheimer's disease in a few years?
Alexander Hardy: I'm very excited about Alzheimer's. I, I think, you know, this is, this is an area where, you know, the industry has once again, I, I don't think it's fully understood, but where the innovation in the United States of this industry has been really extraordinary.
The, the science is enormously hard, but everybody understands the unmet need, and we've been continuing as an industry in Genentech, despite setbacks, we've continued to, to push forward and, and, and, bring forward different approaches. And I think, you know, I think that's enormously exciting. We've, we've got lots of failures in our rear-view mirror, but I'm actually optimistic right now that, that we're gonna see some significant progress, and we, we have a number of different …
John Whyte: In Alzheimer's disease?
Alexander Hardy: In Alzheimer's.
John Whyte: OK.
Alexander Hardy: You know, we have a number of different approaches in research and in development. We're, we're waiting right now for the phase III readout on two phase III studies reading out on one of our late-stage molecules. We'll have to wait for the results. I mean, you know, it's all about, you know, does this change cognition? We've already seen it, it has some effect in terms of biomarkers, but for us, you know, we have to see that profound impact on, on cognition. You know, I, I think this is, is an area where we'll see, you know, tremendous progress.
John Whyte: Right.
Alexander Hardy: I think precision medicine is, is a large part of where we're gonna continue to make progress, which is enormously exciting. If we can make sure the drug is, is being used in that population that expresses a particular form, a subtype of that particular cancer tumor type, you know, I think we can, we can really profoundly improve outcomes, reduce the burden in terms of side effects and reduce the cost to society. So it, it fits the sort of thing that we want to make, we want to see the progress made.
I think also cancer immunotherapy is enormously exciting. It continues to be enormously exciting.
John Whyte: Absolutely.
Alexander Hardy: And, and it offers so much. We're also seeing, you know, new modalities. I mean, we're, we're a company that, that has a history in terms of monoclonal antibodies. We're really excited about the progress we're making with antibody engineering, and some of our nearest, nearer-term investigational molecules are bispecific drugs. I mean, this is, this is enormously exciting. And, and, and then you're talking about the combination of these different approaches. And, and the prospect is, you know, continuing to make improvements on some of the really difficult to treat cancers.
So I think, you know, neuroscience and oncology, these are enormously exciting times.
John Whyte: Are we gonna see partnerships in there? Are we gonna see speed? Are we gonna see diversity? Are we gonna see all those things that we've been talking about?
Alexander Hardy: We're gonna see diversity. We're gonna see, certainly, speed. I mean, you know, it –speed, we're, we're optimizing for speed in a great, a great degree. We're increasingly going from signal-seeking phase I studies where we see a clear sign of efficacy, to then going straight to phase III. Um, this is tremendous risk involved in this, but we, you know, we're, we're doing a better job with the phase, the phase I studies, uh, taking on additional risks, and then this is the area where, of course, you know, regulatory partnerships are really critical where there's that dialogue.
You know, we've seen something that it really, that could, that could profoundly change the treatment paradigm in a particular tumor type. Having that discussion and then the support to go to phase III, uh, which is, which is enormously exciting.
John Whyte: What's the one word you would use to describe the last 20 months?
Alexander Hardy: I would say paradigm-changing. That's two words.
John Whyte: That's two (laughs). It's hyphenated.
Alexander Hardy: You can put a hyphen in there (laughs). But I think you know, it, it, the lasts 20 months has shaken up so many different things, so many traditional industry norms and paradigms. And expectations of the industry within the industry.
You know, I think this is, you know, whether it's health equity, whether it's speed, whether it's partnerships, all of these areas have, have been ... We will not go back. We will not go back to the way it was.
John Whyte: You keep talking about the silver linings, and you said it a couple times in our conversation. You've said it many times in the media. I just want to ask you, why are you so optimistic? You've been focusing on the positive. There's plenty of people that are, you know, very sanguine about, you know, what has gone on the last 18, 20 months. What's different about Alexander Hardy that he keeps saying "these are the silver linings"?
Alexander Hardy: You know, I think it's because, you know, that, that, that the demands on, on the industry and the expectations are so high, and, and we needed to change. Whether it's the topic of, of health equity or speed or transparency and trust. I mean, we've got to deliver on these things, but I think those expectations are really, really clear, and I think when there's really clear expectations and when there's accountability, I think that's when, when things really do change and really do happen. I think that's, that's a large part of why I'm, I'm optimistic about the future.
John Whyte: Well, Alexander, I want to thank you for taking the time today, for all that you're doing to advance the health and science for the American public. So, thank you.
Alexander Hardy: Thank you very much.
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Cite this: John Whyte, Alexander Hardy. Change Makers: Alexander Hardy on the Future of Health - Medscape - Feb 04, 2022.
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