How Can Pharma Incorporate the Commercial Aspect Into Drug Development?

When pharma companies launch a successful product, the process leading up to that point contains many key decisions from various teams across a manufacturer, including commercial. And with science leading to more and more innovations and many drugs coming to market via an accelerated process, it’s critical now more than ever to understand when to bring in the commercial team and how it can help with the development of a drug and its ultimate success in the market.

During a recent webinar, which was part of the Fierce Leaders in Sciences Forum sponsored by Fierce Pharma, moderator Lisa Johnson Pratt, a board member for Assembly Biosciences, Inc., kicked off the discussion by asking what the biggest challenges are for companies that are trying to bring a strong commercial point of view and input into the product development process.

According to Katie Devine, president of the U.S. cardiovascular business for Janssen, a Johnson and Johnson company, as well as the lead for the company’s portfolio in Canada and Puerto Rico, it’s “ruthless prioritization. There’s so much incredible science in the world today, both inside of our own R&D organizations, as well as in the biopharmaceutical industry in general. There’s an incredible amount of technological advancement and scientific discovery going on that could be really, really exciting, and resources are limited. So I think the hardest thing that we do is that ruthless prioritization. Are we going to be first? Are we going to be best? How can we make sure that we don’t just have something that’s going to work in the lab but something that’s going to work in patients’ lives?” Companies, she maintained, need to “consider making sure that innovation has the potential to be successful all the way through the steps in that process.”

Chris Round, president of EMD Serono, Inc., Merck KGaA's health care business, agreed that “this question of differentiation is particularly challenging. If you go back even 20 years, you often had a period of exclusivity, a period that had a lot of direct competition when you launched a new drug or a new clinical entity or a new biologic. These days it seems with transparency and with the focus and intensity we bring to drug discovery, there are always two or three or four or five companies launching a similar mechanism, so finding ways to build differentiation into a program and to keep that current as science progresses, as the trials progress, I think is one of the major challenges.”

“The velocity of science now is extraordinary,” observed Lynelle Hoch, senior vice president of the cell therapy franchise at Bristol Myers Squibb. She explained that manufacturers need “to balance the risk with the benefit as you’re thinking about advancing your pipeline, but also [be] willing to know you can’t answer every scientific question internally.” This means, she said, that companies must be “smart about your horizon scanning, of where you might want to bring a BD [i.e., business development] deal vs. incubating your own ideas internally.” And while making the right choices in prioritization is important, so is “being knowledgeable enough to know when you made the wrong one. Failing fast is OK as long as you fail fast.”

And with this velocity of science comes data that is rapidly evolving, so firms need to make sure to manage this and use their resources well, said Johnson Pratt.

“You kind of have to continually reiterate on the business case, on the probability of success, on the competitive set and try to keep all of that current to make sure that the relevant voices have the right volume,” explained Round. “If the commercial voice is too loud, and we don’t listen to the scientists, and we don’t listen to what’s going on with the mechanism, with the science, that can be a mistake.” So having the right voices participating is crucial. Also important is a continual evaluation of the program and then including senior people, such as the head of research and development, who “can be ruthless, who can be a little bit dispassionate” about products that people may be emotional and passionate about, particularly when they’ve been working on them since discovery. The process is “not easy. But we want to allocate scarce resources to those programs that have the best chance of delivering the most value and the most health gain for society, and hopefully that’s a good proxy for the value to the business as well.”

“What is really important is it’s good to be passionate about science,” asserted Hoch. “The thing you have to make sure you appreciate is the context every single function is coming at the same problem statement and making sure people are rooted in, that the problem statement is no different. The problem statement is how do we transform the lives of the patients through innovation and science? And how do we do it to four more patients and understanding the dimensions from the scientist side and how they’re seeing the science, but then for them to understand from the commercial side what it will take to commercialize?”

According to Hoch, whose company has two chimeric antigen receptor T-cell (CAR-T) therapies on the U.S. market — Breyanzi (lisocabtagene maraleucel) and Abecma (idecabtagene vicleucel) — “what people have to learn about is the notion of being able to learn cross functionally, look at problem statements cross functionally and ultimately come at it with the same goal in mind of how do we treat more patients? I do think once you open people’s aperture to that kind of framework, you do see people gravitating to the same spot. Will you always have to have some tough conversations as we’ve had them internally in cell therapy? Cell therapy is an extraordinarily exciting, complex, but also expensive modality, and you do have to make choices. The cycles times are longer, more complex and more expensive than we’re used to in biologics or small molecules, so we have to be more ruthless than we’ve ever been before.

“And it’s hard when you talk to the scientists about their compound or their process or their technology,” but the product may not be a viable one to pursue, she continued, and they need to know the reason why. It could be that “we’ll never be able to market it, to launch it anywhere outside of the United States because no other market is going to be able to do a health assessment that will give it any value. These are tough conversations but ones if you give them context and education vs. just saying ‘no, that won’t work commercially,’ you’d be surprised at how much scientists want to know why it won’t work commercially.”

So how does pharma “ensure that there is good commercial knowledge early on in that process, and how do we continuously deepen that knowledge through the course of drug development?” asked Johnson Pratt. “When does commercial come in?”

“It’s an incredibly exciting time to be a part of this industry because the science has never been moving more quickly, but also expectations are going up at a rapid pace, and innovation takes a long time,” replied Devine. “I do think it’s important to have that commercial and marketplace understanding very early on, of not just what it’s going to take to demonstrate a meaningful clinical benefit, what it’s going to take to get approval, what it’s going to take to get the right reimbursement profile, is there a significant diagnosis out there so that this is going to get all the way through into patients and be able to help them live healthier lives? I think we have to have that commercial input early on, but then we also have to be willing to revisit if market conditions change because the science is changing so quickly.

“So if there are other programs that have come to market before your drug, and all of a sudden, the expectation of what you thought it would take to break through and have a competitive advantage has changed, you have to be willing to reevaluate that,” she continued. “And those are some tough decisions. I love the conversation about the smaller biotech companies who feel such emotion for their products and their development. That’s a lot of what fueled them, that’s incredibly inspiring, I think, to all of us to find someone whose blood, sweat and tears were collected in every ounce of their development program.” Companies, however, need to determine what the target product profile (TPP) is early on, before the data comes in on a therapy, so everyone is aligned on what clinical outcomes they need to see for commercial viability.

“I think the volume of the commercial voice needs to go up as you get later in the program,” agreed Round. “It can be relatively quiet in the research early, maybe laboratory stage.…I’m a firm believer, particularly in oncology and specialty medicines, that we should let the scientists follow the science and not put perhaps uninformed restrictions on what they do too early on in the process. But when you’re finalizing a minimal acceptable product profile or the actual TPP, that’s a joint effort, and commercial has a right to veto on that. If this is not going to be commercializable, if it is not going to be reimbursed, or it’s only going to be a single-market drug and have a lot of geographic risk associated with it, then I think the commercial voice needs to be strong and heard and listened to….Then that feeds into all sorts of other things, trial design, target indication, comparator drugs, etc., and a full suite of proper market access input for all of the countries where you intend to market it.”

Johnson Pratt noted that she has seen companies “get a little tripped up” with TPPs and “minimum viable product profile vs. an optimal product profile.” At Bristol Myers Squibb, the company starts with determining the optimal target values, Hoch said. “We spend a lot of time on not just the attributes but why. I find that if people understand why that is the optimal product profile, what’s driving that to be the optimal target profile, then the…emotion goes out of it.”

“We’re talking about what it’s going to need to compete in this section of breast cancer, this particular area of lymphoma,” she explained, and how the company can differentiate itself from its competitors.

“If you spend that time up front, then as the profile emerges or multiple shots on goal keep emerging, then it gets a little bit easier to have that debate. I’m not saying it’s easy to have that debate, by the way, because there is always debate.” She pointed to the company’s highly prescribed anticoagulant medication Eliquis (apixaban), noting that the commercial and R&D teams disagreed on the product’s potential early on. That therapy’s success is because the company “listened to the scientists. Sometimes TPP might need to be challenged if the science is telling you something different.…It’s a two-way street on the volume that needs to go in both directions.”

“You have to have a competitive advantage, but you have to go where the science leads you,” echoed Devine, citing Janssen’s multiple myeloma therapy Darzalex Faspro (daratumumab and hyaluronidase-fihj). “We had an incredible product on the market in Darzalex, but it was a six-to-eight-hour infusion for the patients.” Darzalex Faspro is the same medication delivered over a five-minute subcutaneous injection. “You think about innovation, and it’s not always a new molecule.…You have to have an ‘-er’ — it’s better, faster, cheaper….How is it going to make a difference in people’s lives?”

With more companies focused on patient-centered drug development, it’s important to understand when to bring it into the development process, stated Johnson Pratt.

For EMD Serono, “at one level, everything we do, all of our drug development, is patient centric,” said Round. “At the end of the day, we want to get health advances delivered to patients who need it as quickly as possible. But I think there are a number of approaches that are being taken by the industry today.” He noted that “the regulatory environment is much more patient friendly, so the concept of a breakthrough therapy designation — which really didn’t exist 10 years ago — has flourished. We’re able to get drugs to patients faster, we’re able to get them there with confirmatory studies that come along after those initial approaches.” In addition, he said, companies are “taking steps to improve the diversity and breadth of patient representation we have in our clinical trials. This is a key initiative.…This is going to ensure that we have more equitable access and patients have more equitable access to therapies.”

“Because of that nuance, it’s why commercial input is needed earlier,” added Hoch. “Before you would have to go through Phase III,” but “that velocity has really changed.” She noted that “health authorities around the world…are working awfully fast to figure out how we can bring this innovation to patients faster….It’s very different today from 10 years ago, even five years ago.”

Round asserted that bringing in real-world evidence to the drug development process “is extremely important going forward. Clinicians are asking for it; they need this data to help them determine how to think about products and how to think of them in practice….We often have a lot of clinicians who will approach us with ideas to run these studies.” Because this information can be used to inform reimbursement and the ability to access some markets, this data should probably be brought in two to three years before a therapy launches, he recommended. Then that data set will be supplemented through “the first five, six, seven, eight, nine years of a product’s life, and then we can continue to add to it and add to the body of knowledge that clinicians can use to help them with their decisions.”

It’s “so important to providers and patients that they’re staying up to date with the latest and greatest science,” stated Devine. “The day the drug is approved, there’s clearly a robust body of scientific evidence on efficacy and safety, but it doesn’t end there. In some ways, it begins there. And that’s where there’s an expectation that we hold ourselves accountable to continue to learn throughout a product’s life cycle.”