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A recent roundtable of pharmaceutical CEOs, and moderated by Dr. Scott Gottlieb, discussed pressing concerns around the pandemic, including clinical trials, product launches, keeping employees safe and the future of the pharmaceutical industry.
Michael J. Hennessey Jr., President and CEO of MJH Life Sciences, the parent company of Pharmaceutical Executive, convened a closed roundtable of pharmaceutical CEOs in mid-May to discuss the industry’s pandemic response and preparations for an as-now uncertain future. The virtual roundtable was moderated by Scott Gottlieb, MD, former FDA commissioner and, more recently, the go-to, non-partisan expert on COVID-19 developments and CNBC Contributor on the topic. Gottlieb received kudos from all the participating leaders as the voice of science and reason, providing the public balanced insights as the pandemic unfolds. Overall, the gathered leaders, representing various therapeutic areas, revenue-sized companies and states of commercialization, are optimistic and predict the industry will rise to the myriad pandemic challenges, ultimately transforming public perception and elevating science.
Gottlieb provided a snapshot of where the United States was in relation to COVID-19 in mid-May before observing the specific nuances faced by these leaders and asking for their experiences, which included working with the FDA around COVID therapeutics, as well as other therapeutic areas; clinical trial issues such as protocol amendments, trial suspensions, or dwindling recruitment; product launches; patient access to therapies for disease management and outcomes; and longer-term business operations.
Regeneron has been on the front-lines of COVID-19 therapeutics development using its VelociSuite technologies to develop a novel cocktail of fully human antibodies that are specifically targeted at the SARS-CoV-2 virus. It jumped into gear to address COVID-19, said CEO Leonard S. Schleifer, MD, PhD, in the early part of January, identifying the most potent and effective virus-neutralizing antibodies and scaling them up using Regeneron technologies, with the expectation of entering clinical trials in June.
At the other end of the spectrum, is Michael Castagna, CEO of MannKind, whose COVID-19 “a-ha” moment was around manufacturing and the company’s dry powder capabilities. He asked: “Is there an opportunity for us to take someone else’s therapy and replicate that into our inhaled platform and scale-up that up?”
Clearly, none of the potential treatments can advance without regulatory authority approval. Michael G. Kauffman, MD, PhD, CEO of Karyopharm Therapeutics, described how he and co-founder Sharon Shacham decided to look hard at COVID-19 and test low doses of its anti-myeloma drug, which has both anti-inflammatory and antiviral components. Most striking to Kauffman was the speed with which the company was able to secure a clinical trial protocol “in a disease that we and most other people knew nothing about.” Within two weeks, the protocol was turned around by 10 different global regulatory bodies and it opened up for patients in three weeks. It really tells you what is possible when most obstacles are eliminated,” said Kauffman. “And this is tenfold faster than we’ve ever done in the past.”
Incyte has been working on potentially treating COVID-19 associated cytokine storm. President and CEO Hervé Hoppenot said of Incyte’s efforts, “Although virology is not our area of focus, we quickly realized that inflammation may play a key role in severe COVID-19 patients and mobilized our teams to initiate trials to hopefully answer some key questions.”
Like Kauffman, Hoppenot also witnessed efficiency – RUXCOVID study protocol was written with its large pharma partner, Novartis, over a weekend to submit to the FDA on a Monday morning. “The level of urgency was very clear,” he said. “We quickly decided to move forward with the RUXCOVID study where we are trying to determine whether treatment with ruxolitinib can prevent the inflammatory cascade that results in serious complications in many patients infected with the virus.”
This level of cooperation, collaboration and speed has not gone unnoticed outside of COVID-19 trials. For example, in oncology, Hoppenot noted Incyte had three reviews ongoing with the FDA’s Oncology Division during the early stages of the pandemic, of which two are now approved. Said Hoppenot, “There were all kind of issues including the inability to perform site inspections; it was interesting to see the adaptability of the FDA and the commitment to keep things moving.”
Kauffman concurred. “[The oncology division] has moved with our sNDA. They haven’t slowed down, which is important for cancer patients.” So too with Clay B. Siegall, PhD, president and CEO of Seattle Genetics Inc., who gained two approvals during the early pandemic in breast cancer and bladder cancer. Siegall said, “The FDA has been incredibly collaborative. Rick Pazdur has been innovative and forward-thinking; driving a number of initiatives to rapidly bring important medicines to patients in need.”
Liz Barrett, president and CEO of UroGen Pharma, said the pandemic began during the review of its first NDA, and found the FDA was very engaged, and received approval prior to the PDUFA date for its therapy, the first non-surgical treatment for upper tract urothelial cancer. She said, “I think the agency really understood the high unmet need and wanted to get this product to patients as quickly as possible.”
FDA has also responded outside of oncology. Steven Lo, president and CEO of Zosano Pharma, whose NDA of its microneedle patch technology with a migraine drug was submitted in December, said: “One of the big questions for us was what’s going to happen with the FDA? But our NDA was accepted in March, right on time. We have had productive interactions, and it certainly appears the FDA is humming along quite fine.”
Of course, amid FDA’s approval output during this period, the subsequent product launches will require attention in the pandemic environment.
Tim Whitten is president and CEO of Taiho Oncology, which has a PDUFA date in August, and is preparing to launch its product. “Our sales representative are getting trained virtually. It goes beyond just disease training and product training. We want to understand how our customers want to interact with us. In addition to ensuring our field personnel’s adherence to new state rules and requirements in terms of PPE and similar requirements, we’re training our employees and our sales reps and MSLs on how to conduct better virtual interactions – everything from logistics to lighting, giving them better cameras – so that when they do have access they’re able to have an effective interaction.”
“As they say, ‘Necessity is the mother of all invention,’” noted Barrett. “As an industry, we have talked about digital for a very long time and we all have digital as part of our plan, both from a commercialization and a development perspective. This is forcing us to accelerate the adoption of digital tools.” UroGen was launching its aforementioned approved Jelmyto on the day of the roundtable at the American Urological Association’s annual meeting, with its physicians presenting virtually. Barrett shared, “Over the last couple of weeks, we had face-to-face Zoom meetings with physicians. We have shifted our events and meetings to virtual, and we’ve had willing audiences of physicians and patient groups who all want to engage.”
Looking forward, Lo asked the participants what launching products might mean post-pandemic. Zosano, should it receive approval on its PDUFA date in October, is re-thinking how to allocate resources. “We have to acknowledge the fact that not every physician is going to be happy to see a sales rep or a medical science liaison walk into their office, and we have to reshuffle some of the targets in terms of the number of people that you would need for a launch in our particular space.”
Gottlieb wondered if oncology clinical trials were a special case, as most studies that have been suspended are non-cancer related.
Siegall seemed to think so. “Our trials are still ongoing and enrolling. I think oncology is a special case. Outpatient oncology facilities have largely stayed open,” he said. “It gets complicated if you need PET scans or if you need to go to a hospital for a test; that can make a trial more cumbersome. But I think cancer is unusual in that the clinical trials are still going strong. In different, non-cancer applications, it’s bumpier.”
John F. Crowley, chairman of the board and CEO of Amicus Therapeutics, spoke to the rare and life-threatening disease aspect, citing its Phase III program in Pompe disease. Crowley shared that Amicus’s therapy was being made in China with WuXi Biologics, in a program that required, logistically, getting product patient-by-patient, site-by-site, with about 60 different sites on six continents. “The rare disease community-the patient groups, the individual investigators, the hospitals, the IRBs- stepped up beautifully,” he said. “In one of our studies, we had to move patients to home infusions. We thought that could take up to six months. We did it in less than three weeks for all those patients.”
“Oncology-focused biotech Exelixis was executing on nine pivotal trials globally, with plans underway to initiate three additional studies, when the health crisis ensued.” Michael M. Morrissey, PhD, the company’s president and CEO, said that despite its scalable technology platform and seasoned and sizable staff, “it’s been a workout.” He described going to a “SWAT team level where we’re literally tracking every trial, every patient, every scan, every delivery of drug literally every day.”
Exelixis also unblinded a large global pivotal trial with Bristol Myers Squibb, which Morrissey said went well even though it was a huge undertaking to achieve remotely with two different companies on two different coasts. “It reinforces the idea that if everybody’s aligned, and there’s the right level of leadership and commitment, you can get a lot done under less than optimal circumstances,” he noted.
For Whitten, though accrual has slowed, Taiho Oncology didn’t consider closing clinical trials. “We have several trials for which we finished enrollment, but still have patients in those trials. We’ve put much greater scrutiny on ensuring patients and investigators get reminders to come in for scans and bloodwork. And so far, we haven’t had one patient who has missed a scan or their bloodwork. It’s a balancing act. You don’t want to put an undue burden on your investigators by overcommunicating, but we felt it was really important that we maintain quality.”
Barret, peering at the future of clinical trials, noted the likelihood of more virtual activities such as wearables and monitoring patients. She also noted on a recent call about UroGen’s ongoing studies-they’ve shifted from purely traditional studies to real-world evidence (RWE) studies, which she believes will be a continued shift in drug development.
Gottlieb too referenced RWE, and said, “Trends that have been underway for a while in terms of different kinds of evidence generation, different kinds of clinical trial designs, are going to be accelerated in this environment as both companies and regulators realize that we’re going to need to do things differently for an extended period of time and maybe in perpetuity as a result of COVID.”
ImmunoGenesis was the only startup represented at the roundtable. CEO and President James Barlow, Jr., believes its lead asset provides a superior foundation of PD-1 pathway blockade. The company is trying to raise Series A funding; the pandemic has made it easier to reach investors, Barlow said, and there is clearly still funding available but he’s noticed some hesitancyas certain VCs are focused on shoring up existing portfolio companies rather than speculating on new ones.
However, since ImmunoGenesis is trying to get into the clinic rapidly in a very competitive immuno-oncology environment, the choice of vendors for pre-IND activities is important. While working with MD Anderson Cancer Center initially, it was impacted by shutdowns. Barlow said, “Moving forward, I think we need to look at non-academic choices, the Charles Rivers of the world, to make sure that we can keep things moving and keep hitting our timelines.”
UroGen’s Barrett noted pandemic effects on its current Phase IIb study, which has seen a delay in patients coming in for follow-up, due to safety concerns. She predicts a shift of trials from large academic centers into large community practices because patients will be less inclined to enter institutions also treating COVID patients. “Much of the recent literature shows that up to 40% of cancer patients are not going in to see their doctor,” said Barrett. “As an industry, we owe it to the patients to help them understand that it is safe and that they need to make these visits because we don’t want them to delay treatment.”
Access to safe treatment environments for patients is closely coupled with their ability to pay for treatments. For example, patients who can’t afford or have inadequate insurance can use Taiho Oncology’s patient access program to get their drug for free from the company. Said Whitten, “Once the pandemic hit, for every three patients that are getting our drug and we’re getting reimbursed, we have one that’s getting that drug free. That’s increasing and I think it'll continue to go up because our drug is for metastatic gastric cancer and metastatic colorectal cancer, which tends to affect seniors. And if you’re on Medicare, relying on Social Security, it doesn’t matter if you have a co-pay of $300 or $3,000, you can’t afford that drug. We’re very fortunate we can help meet the increasing need and ensure those patients have access to their drug.”
Similarly, for Zosano Pharma, Lo explained: “Most of us have set aside resources for copay assistance. We always want to take care of patients. I think it’s fair to say, in this environment, we have to make sure we don’t underestimate the amount of patients who could become or are uninsured, or who would need more copay assistance or help. That is true in the migraine space, and it’s caused us to rethink our financial models around patient resources.”
Incyte’s Hoppenot believes the pandemic has put a “magnifier on the dysfunction of the healthcare system” in the United States as it pertains to patient access to doctors, tests and treatments. “It was very clear, very early on that access to doctors and access to tests were prevented by the co-pay organization used by insurers. They are penalizing people for seeing their physicians. They are penalizing people for getting prescription drugs, for getting a test. [The pandemic] started at the beginning of the year when many people are still in the deductible phase of their plan. I think this had an impact on the speed at which this disease was treated and diagnosed compared to other countries. This issue of access needs to be addressed.”
For many of the leaders, ensuring employee safety and maintaining communication during and after the pandemic is key. Crowley created a taskforce of 100 (of its 600) employees to “Help me to reimagine what Amicus looks like on the other side of this. We call it our R3 project - rediscover, reimagine, and reinvent Amicus.” It includes questions about how, when, and where do the employees work? It could be that some jobs will be five days a week in the office, others entirely at home, or a hybrid. “I think when we’re together, let’s not be running from meeting to meeting,” said Crowley.
Siegall thinks coming out of COVID-19 that his company’s commercial staff will be more remote, and thus the amount of real estate needed will be less. Conversely, Seattle Genetics owns and operates one manufacturing center in the United States, and is going to build a second. “We are going to bring in more manufacturing that we can control,” said Siegall.
Castagna noted that the pandemic has been an opportunity to lead employees through tough times. “We haven’t furloughed or laid off anybody and actually hired 13 people over the last two months,” Castagna said of MannKind.
Taiho Oncology has also onboarded about 20 people during the COVID-19 pandemic; Whitten is happy to see people that are willing to join the company amid the difficulties of determining culture fit in a virtual environment. “Our motto is PACT. P for people, and that includes employees and patients, A for accountability, C for collaboration, T for trust,” explained Whitten. “How we make decisions will not change from those operating principles. What will change is how we implement and operationalize some of those decisions.”
While lessons applied internally will have great impact, the external learnings and achievements may herald a new beginning for the biopharmaceutical industry.
With Hoppenot, the focus is on his experience with Novartis in the decision to move forward with the RUXCOVID trial. “It was a new way of thinking; one that focused on quickly finding solutions to problems in a highly collaborative manner,” he said.
Kauffman’s similar lightning-speed experience getting into trials led him to observe that, hopefully, “we’ll be able to at least not go back to six-to-nine months to start-up and begin enrolling on a protocol, especially for patients with severe illnesses like cancers.”
Gottlieb shared, “This once-in-a-generation pathogen has put a spotlight on the life sciences industry like nothing really has in modern times. And everyone’s really looking to the industry for hope and for a way out here, and it’s ultimately going to be something definitive with our technology that quells this epidemic and gives us a definitive end to it.”
Barrett added, “I hope we will take this opportunity to ensure we don’t revert back to the negative public sentiment of our industry prior to this pandemic. We need to take advantage of educating the typical consumer about our industry and the benefit we bring to human health.”
Crowley said, “Just like physicians and nurses have taken an oath to heal the sick, we as innovators in this business have taken an oath to make the best medicines and to ensure access as broadly as possible. And I think by the actions that we’ve shown and hopefully will continue to show, this will be our finest hour.”
Schleifer concluded, “This is an existential moment for the industry. I think we will rise to the occasion. I am excited about the number of different companies trying incredibly novel approaches for vaccines, the number of companies who are trying different therapeutics. We have to do it scientifically, and we have to do it in an affordable, successful way. If we do, we’ll change industry and, frankly, we’ll change society for a long time.”