Product development is unique in biopharma in the degree of separation between product developers (R&D scientists) and end users (patients and practitioners). While R&D focuses on questions like “Is it possible to treat this disease?” and “How can we drug this target?”, commercial organizations focus on questions like “Why does a physician prescribe these drugs?” and “What kind of drug do patients and providers want?”
In large organizations, it’s possible to have a very productive R&D career without ever running into someone from the commercial side. (In fact, many scientists will even say this is a good thing to protect creativity, though this is a topic for endless debate.) But working together with commercial leaders can give drug hunters a helpful perspective on what the key issues are that determine just how useful future drugs will be to society.
Here’s a few minutes with featured reviewer Anthony Vaganos, a commercial leader at GlaxoSmithKline with perspective from several product launches.
Anthony is currently an oncology global marketing director at GSK focused on pivotal trial investment decisions, launch planning, and marketing of oncology therapies. He previously worked at Genentech in commercial functions on multiple franchises including hematology oncology, HER2 breast cancer, neuroscience, and rare disease, and started his career at the US Agency for International Development (USAID).
While getting his start in the nonprofit world working to provide humanitarian assistance to developing countries, Anthony feels that so-called “Big Pharma” – particularly the commercial side – has gotten a bad rap. “Prior to COVID-19, the Pharma industry got the worst rating from people – worse than the federal government!” he laughs ruefully, noting that even those within the industry often view the commercial piece as the “dark side.” He adds, “I wish there was a greater understanding of the value we bring. Generating the resources to invest in technology and innovation is what it’s all about. The pace of innovation in a nonprofit is so much slower; if we were just a government-funded entity, there wouldn’t be that pressure there to bring innovative solutions to patients.”
Inspired by the Game-Changers
Innovation in drug discovery often means taking risks, which can lead to game-changing discoveries. For Anthony, one of the most captivating stories of successful risk-taking is the smallpox vaccine:
“Back in the 1700s, when people were dying of smallpox, a physician noticed that people who were taking care of cows and got something called ‘cow pox’ never actually developed smallpox. And that transitioned into the whole idea of using a weaker virus as a way to inoculate someone. Of course, now, with mRNA, that concept is fading with new technology. But to me, just the idea that you would infect someone with a weaker virus in order to prevent a more severe disease takes a lot of bravery and courage from both the patient and the practitioner. Today, smallpox really doesn’t exist in the world, so taking that risk, in fact, led to a tremendous breakthrough.”
Another breakthrough, in Anthony’s view, is what he calls the “OG of precision medicine”: Herceptin, one of the first companion diagnostics. “Herceptin really changed the game,” he says. “Before Herceptin, HER2+ breast cancer was just about a death sentence. But nowadays, it’s thought of as one of the easier types of breast cancer to treat or at least one that has a better prognosis.
What He Thinks About Day-to-Day
The successful launch of a new drug depends on a number of factors, and even a successful launch doesn’t guarantee that a drug will prove to be commercially viable.
“The main challenge is understanding who a drug will work for best and then being able to articulate why it’s worth putting someone on that therapy,” Anthony explains. “That means making sure people are aware that the drug is available, what it can do, and how to make the risk/benefit trade-offs.”
He adds, “Of course, once someone starts on the therapy, helping them stay on the therapy is important. For that you’ll need the right tools and support programs for patients, physicians, and nurses. For patients, this might include adherence support like a phone app that reminds them to take their pills or stay hydrated. It might also include a hotline for nurses, who are on the front lines in dealing with side effects, to make sure they have a certain comfort level in managing a range of adverse events.”
Another challenge is readying the launch juggernaut amid the inevitable fog of uncertainty surrounding whether or not a drug will be successful. Similar to what often happens on the R&D side, a lot of effort could be for nothing if a drug doesn’t end up working. Anthony describes the process:
“In marketing, you have to be ready in advance, but how do you know if your drug’s going to get approved or not? Late-stage product development will assign a probability of launch, assessing the regulatory and technical risk, as well as the likelihood of approval. In theory, the minimal TPP (target product profile) is what you need to hit to be commercially viable. You’ll know once a trial is unblinded whether it hit the TPP or not. Once we know the data are good enough to file, and once the approval happens, then the sales aids, websites, guideline submissions, etc., all have to be ready to go.”
Hurdles remain even after a drug is approved. The big question: Will physicians use it?
“There is the theoretical vs. the practical specific. In oncology, a common minimum yardstick is the three-month improvement in overall survival. But there are other factors to consider. Taselisib is a great example – it had a positive study but it has not been filed or approved
On What Makes a Useful Oncology Drug
The last three decades have seen a revolution in cancer treatment. Efficacy remains a top priority, but it is no longer the sole consideration. Because of the growth in treatment options, safety and quality of life now play a greater role in the risk-benefit calculation by patients and physicians.
“The big picture is that in the last 30 years, drug hunters have discovered therapies for almost every cancer!” Anthony exclaims. “When the first targeted therapy came out, everyone eligible went on it. The key is that today there are choices—it becomes more than about efficacy alone.”
It’s Best to Be First to Market…
“A classic tenet of business is that first to market gets the most market share,” says Anthony. “What that means for oncology drugs is that the most product experience does the best. Physicians don’t like surprises – they use something a lot, their own real-world experience is that it works and they know how to manage the drug, and they don’t want to switch to something else. Good experience with a product, then, results in habit even when other products come out.”
But if You Can’t Be First, Be Best
Efficacy, manageable side effects, and dosing are the keys to what makes a best-in-class cancer drug. Naturally, efficacy is critical, but side effects can’t be severe enough to cause a doctor to reconsider whether a patient should remain on a particular treatment. And with the array of choices available today, another factor comes into play: dosing.
As Anthony points out, “The big change in oncology is how long do you have to be on therapy? Is it a two-week course of treatment, or being on therapy until you progress, which could be months or years? The differentiator for being best-in-class used to be efficacy/safety; now it is efficacy/safety/dosing. A great example is venclexta for CLL, which is a fixed duration of treatment vs. treatment to progression. You’re on venclexta for a fixed amount of time, and then you’re done. Patients want to be reminded that they’re normal people again.”
Naturally, safety is right next to efficacy when it comes to creating a best-in-class treatment.
Anthony: “For safety, are you looking at something that is manageable or reversible? Both are big. It’s a question of reducing the dose and seeing the side effect go away vs. permanent injury, which really ups the stakes for physicians and patients. In hematology oncology, physicians are very familiar with adverse events like thrombocytopenia and/or neutropenia and these are things that won’t necessarily impact a patient’s quality of life. On the other hand, a symptomatic side effect like GI issues can be very concerning because it can be severe enough for a patient to quit therapy.”
On the Growing Role of Safety for Oncology Drugs
In fact, safety is becoming more important as more options become available, particularly with regard to combination therapy.
“Combinability has a big impact on safety – we’re finding that you can combine many therapies with chemotherapy in oncology,” Anthony explains. “But chemotherapy is very toxic. If the other drug is very toxic, does the combination become too toxic? Rituximab, for example, is administered in a five drug combination. Toxicity can be problematic with combinations. The sum may be way better than each individual drug, but does the combination itself just become unbearable?”
What He Wishes R&D Organizations Knew
“What do I wish R&D organizations knew? I wish you all had crystal balls!” Anthony laughs. “I would say, to the degree you can, think not about today but about what you’re going to do with a drug in five or ten years and how you’re going to compete. Are you going to be first? What’s the market going to look like in that time? Don’t be reactionary – be forward-thinking. Talk to commercial people earlier. Consult early on with the people who are going to try to differentiate. Is what you’re working on going to be a mono or combination drug? If it’s a combo, for instance, maybe you want to optimize more for safety.”
What Excites Him About the Future
Anthony is bullish on the future of drug discovery.
“There are a couple of areas that I find pretty exciting,” he says. “One is CT [circulating tumor] DNA and the potential there to really identify disease at a molecular level before it’s actually manifested in the body or even to prevent disease. There’s just a ‘wow’ factor with the idea that you could treat patients in the very early stages when you would anticipate that prognosis and outcomes could be that much better.
“Another interesting area is the world of AI/ML [artificial intelligence and machine learning]. If the last decade was all about big data, this decade is about using AI/ML to parse through those large data sets, which will really increase our R&D productivity.
“That’s a crucial point. Because the more productive we can be with our R&D investments, the more resources we will have to invest in R&D to generate the power to find even more new drugs.”
Thank you Anthony for sharing your perspective on drug discovery with us!
If you want to read more from industry leaders, check out our other interviews:
- “Don’t Work on Things That Don’t Work” – Kim Huard
- “It Takes a Village” – Joachim Rudolph
- “It Always Seems Impossible Until It’s Done” – Romyr Dominique
- “Shaken by An Unexpected Patient Connection” – Julien Lefranc
Feel the same way, or have something else to share? Please get in touch!