Biopharma leaders know the sobering reality that drug candidates face a 90% failure rate in clinical trials. A failure is much worse when it happens late in the game, though, which is why many companies have adopted the maxim "fail early, fail fast."

Unfortunately, sometimes a late-stage failure is unavoidable for a variety of reasons. For smaller companies in particular, the ability to get past the setback and find ways to succeed takes both strong leadership and scientific depth.

When AVEO Oncology’s cancer drug Fotivda faced an FDA rejection in 2020 to treat patients with refractory renal cell carcinoma — despite having been approved for the indication in the EU in 2017— the outlook appeared bleak. But in March 2021, Fotivda finally gained the FDA’s OK for the indication — and what happened in between was an eye-opener for AVEO CEO, Michael Bailey.

"The FDA rejection was a pretty big setback for the company," says Bailey. "What adversely impacted the U.S. regulatory review was a one-way crossover companion study that was instituted with the best of intentions by the leaders of the organization at the time. They wanted to ensure all patients had access to the therapy, so patients in the control arm were later offered Fotivda. The problem was, that made the overall survival endpoint uninterpretable."

When phase 3 setbacks occur, Bailey says it’s important to persevere and focus on the main objective: the patient.

"We face an incredible number of setbacks along the way," he says. "One of the things I say to my team is if we're in a conundrum and we've got a difficult decision to make, a simple question to ask is, ‘What's the best for the patient?’"

Here, Bailey shares his view on overcoming adversity with promising therapies, what leaders in the industry need to do to succeed and how to anticipate related trends.

PharmaVoice: As CEO of an oncology-focused biopharma company, can you share what is front and center for you as you seek to drive successful outcomes?

Michael Bailey: It’s such a dynamic market that it's absolutely critical that you establish and communicate a clear mission, strategic vision or direction, and then a well-defined path forward. Stay focused and optimally leverage limited financial and personnel resources. The worst thing that a leader can do is chase every shiny object.

The second challenge is the competition for human resources. Especially here in Boston, we've got an incredible pool of intelligent, driven people who can go anywhere, and COVID has thrown another twist into this whole thing because now you don't have to be geographically constrained. So that's created an incredibly competitive environment for human resources. As an organization you have to attract and retain these people, and that means creating a positive culture that is driven by a compelling mission, offering work-life balance.

The third element is you have to stay on your toes and keep up with the literature not only on the business side, but critically, the science in terms of how patient treatments are evolving. Success means being able to anticipate where the market is going to go well in advance, because clinical trials take years.

What did the setback of a failed phase 3 trial teach you and how did you help the company remain resilient?

One of my favorite sayings is that there’s a fine line between perseverance and insanity, and what I mean by that is that perseverance is a wonderful value but you just can't just keep running into a wall. If you have a setback, you have to really understand what went wrong and what you can do to correct it, and even ask yourself whether it is worth persevering.

In our case, we knew that Fotivda worked and that the setback was the result of a bad trial design. So we knew it made sense to conduct another study. It was also an important lesson in not just doing a better job listening to the regulators but paying heed to their body language. At the end of the day, the FDA wants drug developers to be successful, so embrace them like a partner.

After that initial setback, and now one year on from a successful approval, what are some key takeaways you can share on what it took to get there?

Oncology is very evidence-based and for oncologists to be able to make informed decisions, we as an industry have to provide them with robust data from randomized phase 3 trials. Also, remember that every function in the company plays a critical role. As you’re progressing through different stages, the spotlight inevitably is on one aspect — be it clinical development, regulatory, etc. — but we have to keep our eyes on all of these critical functions or those are going to be the places where your next problem is going to come from. Manufacturing is a perfect example that often is not a spotlight, but if you get that wrong, you are going to be in big trouble.

What are some key developments in the industry that are integral for all biotech leaders?

Very recently the FDA had a panel discussion on a new program called Project Optimus proposed by the agency’s Oncology Center of Excellence, which is really trying to focus on patient palatability, or quality of life, versus just pushing drugs to the maximum tolerated dose. We’re seeing a growing trend to more holistically focus on the patient experience, and we feel we're contributing significantly by providing a drug that has unsurpassed efficacy but better tolerability so that the patient experience can be a positive one.

We have started a phase 3 study for a second line of treatment where we’ve decided to go with a lower dose than we would use as a single agent to make sure that the tolerability profile for the patient is optimized.

Another important development is the growing trend to collaborate. As innovative therapies emerge, we need to combine different mechanisms to advance the patient experience. But no one company has every solution, so to optimize these kinds of combinations we need to collaborate, not just with a focus on profitability but more importantly with a focus on patient outcomes.

I advise any biotech leader to bring the patient perspective into early development and focus your resources on products that are really going to create value — not just financial resources but also recognizing that clinical trial patients are an incredibly valuable resource and should only be brought in for meaningful clinical trials.