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From the Editor-in-Chief: Within Ourselves
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Jim Allison: Breakthrough Traces the Unexpected Creative Paths of a Scientist and Immuno-Oncology

Mary Caffrey
A review of the documentary on the life of James P. Allison, PhD, of The University of Texas MD Anderson Cancer Center, co-winner of the 2018 Nobel Prize in Physiology or Medicine. 
In the early 2000s, Medarex and Drakeman were biotech darlings, but for every fan, there were skeptics. The business section of my former newspaper, the Times of Trenton, dutifully published the quarter-by-quarter losses for the company, which was based in nearby Princeton, New Jersey. “Sales ballooned but falling licensing revenues caused losses to skyrocket last quarter and last year,” began the March 19, 2003, article in which Drakeman warned, once again, that things would get worse before they got better.22

It turns out that financials of immuno-oncology matched the biology. Breakthrough does an outstanding job of explaining how Allison, fellow scientists, and BMS not only had to develop a drug that worked but also had to persuade the FDA to develop a new paradigm for approving a drug that worked differently. Harnessing the immune system to take up the fight, instead of killing cancer with poison, means tumors will grow before they shrink; thus, approval should be based on overall survival. This was a tough concept, even for very smart people.23

Which meant Allison couldn’t be just a scientist. He had to be a pain in the rear. And he was.

Matt Richtel of The New York Times is more tactful in the film. “You don’t know whether the new idea is something potent or deadly,” he says. “It takes a really powerful idea combined with someone willing to push it forward to make it happen.”

Skepticism followed ipilimumab at almost every step. On November 9, 2004, the day BMS announced it would invest $25 million with Medarex to develop the agent then known as MDX-010, BMS’ shares fell, at that point down 17% on the year.24 On May 7, 2008, a month after Pfizer’s bombshell and weeks before the American Society of Clinical Oncology (ASCO) annual meeting, the FDA announced it wanted more data on ipilimumab. One analyst told reporters that ipilimumab’s ASCO data would have to outperform the antibody Pfizer had just abandoned for ipilimumab to be commercially viable.25 The witnesses in Breakthrough testify that BMS’ decision to invest in more studies went against convention. BMS acquired Medarex not long after the FDA’s initial thumbsdown; an analyst said this was likely, given what the press called “Medarex’s string of drug failures.”25,26

Allison knew better. Woven through Breakthrough is the story of metastatic melanoma patient Sharon Belvin, given a diagnosis and treated with chemotherapy days before her wedding at age 22. Ipilimumab’s ability to make her tumors disappear told Sloan Kettering oncologist Jedd D. Wolchok, MD, PhD, that something big was happening. Belvin is now cancer free, and she and Allison each share the story of the day they met at the clinic in 2006.

“Until then it was just numbers; it was a concept,” Allison says in the film. “She was the first patient.… Now she has a family, 2 beautiful kids.

“I still choke up when I think about that.”


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