Michael Lewis discusses the Halaven molecule. Photo by Kevin Harkins.
As Michael Lewis sits at the table in his office at Eisai Inc. in Andover, looming nearby is a white board sketch of a mountain. Or what we’re calling a mountain. Eisai is a drug company, and Lewis is president of pharmaceutical science and technology. So the sketch is actually of a molecule. But Lewis is mercifully aware that he is talking very hard-core chemistry with very non-chemists, so out come the similes.
As he expounds on the Japanese-owned company’s recently approved, Andover-made breast cancer drug, Halaven, hoping against all reasonable odds to help his guests appreciate the mind-bending science and 18-year journey that produced a cancer fighter with more real potential than anything they’ve seen before, we are at various points baking a cake, building a skyscraper and captaining a supertanker. But scaling a mountain is the one he uses first, and the one that works best here. Because anyone who has ever looked up at a mountain knows that the second you do, you’re involuntarily assigned to one of two groups: The people who ask how soon we can start climbing, and everyone else.
Michael Lewis Ph.D.; Kenichi Nomoto, Ph.D.; Frank Fang Ph.D. Photo by Kevin Harkins.
Eisai’s Andover buildings are filled with the first group.
They had to be. In the quarter century since it was discovered in a sponge by a deep-sea diving Japanese chemist, the halichondrin B molecule has gotten attention for three main things: being from a sponge found by a deep-sea diving Japanese chemist (that is super cool; nobody disputes this), the wonderfully nasty things it does to cancer cells, and its legendarily complicated structure. Given a few millennia, nature can really do some amazing things. Even after famous (to chemists, anyway) Harvard professor Yoshito Kishi figured out how to make a simpler version in the lab, it remained a monster.
The notion of turning the halichondrin B molecule into a drug was a mountain so big nobody could see the top. More accurately, this thing frightened most of the pharmaceutical world into believing there might not even be a top. In an industry that’s practically all risk — the vast majority of drugs that make it to clinical trials die a costly death in phase one — this was too much of it. Everyone else stood at the bottom of the mountain, shook their heads and walked away, and they didn’t bother hiding the giggles as they passed the Eisai crazies lacing up their boots.
The FDA approved Eisai’s Halaven™ (eribulin mesylate) in November 2010. Courtesy Eisai, Inc.
“To be honest,” Lewis says, “most people outside the company thought we were lunatics.”
But lunatics make the best stories. Frank Fang is a chemist who worked on halichondrin B with Kishi at Harvard before moving down South for a while, only to end up being pulled inexorably back to the molecule in Andover like a salmon to a spawning site. John Orr had a job at a pharmaceutical giant where the molecules “weren’t all that interesting,” so he jumped to Eisai for the scientific thrill of figuring out how to manufacture what the FDA would eventually call the most synthetically complex drug it ever approved.
The drug was derived from the marine sponge Halichondria okadai. Courtesy Eisai, Inc.
Lunatics also lead you to more lunatics. The disarmingly polite Kenichi Nomoto will give you as much time as you need to understand his role in determining how the molecule worked in animals, but is more interested in giving credit to Bruce Littlefield. Littlefield was lured from Eisai by Harvard Medical School in 2009, but he personally did Eisai’s first experiment on the molecule 19 years ago, and given the chance to talk about it he will practically offer to drive to your house to do so. Not just because he believes it “has the potential to be the best cancer drug out there.” Not just because “no matter what I do for the rest of my career, I’ll never beat what we did in those years.” It’s also because he wants to talk about more Eisai-Andover guys like Melvin Yu and Murray Towle.
“Our strategic edge was that we knew nobody in their right mind would be trying to make something out of this,” says Littlefield, acknowledging that they probably wouldn’t have been allowed to try either if Eisai hadn’t been desperate to make a splash with its then-tiny U.S. operation. “We knew the competition would be zero, and we knew if we achieved this, it would blow everybody out of the water.”
Well … boom.
“This drug,” Orr explains, “is a 62-step synthesis. Companies don’t go much over seven, eight, nine steps.”
Jennifer Acker, principal researcher, Quality Control Chemistry. Photo by Kevin Harkins.
Once they knew they could produce enough for clinical trials in humans — those 62 steps take almost two years to finish — it needed to do something good, and the molecule delivered. In late-stage breast cancer patients who’d seen other chemotherapies already fail — the group it’s currently approved for — Halaven extended survival by an average of two to three months. If that doesn’t sound significant, take two notes: The first is that no drug had ever done that before; the second is that you should talk to a late-stage cancer patient about the concept of time.
But showing actual improvement in sick people, while super, comes right before showing the FDA you know what you’re doing. It’s not enough to prove you can do the whole 62-step dance reliably. You’ve got to prove you know what’s happening and why every step of the way, and help the feds understand it, too. Wondering why those simple molecules look so good? The paperwork alone is enough to crush a human soul.
Now having done it, they want to do it again, as much and as soon as possible. Trials are ongoing for earlier stage breast cancer, lung cancer and a slew of other applications. There’s quiet optimism inside Andover’s walls that we’re only seeing the beginning, and not-so-quiet expectations — perhaps better described as pressure — coming from Eisai’s global home in Tokyo. The CEO publicly declared it could become a billion-a-year earner if more trials go well.
Not that there’s anything like a guarantee with cancer. And if anyone needed a reminder of how tough the drug business is, Halaven’s FDA approval party in November was followed a few months later by Eisai’s announcement of 900 impending layoffs worldwide, thanks to losses from the patent expiring on its Alzheimer’s drug.
It helps, though, that the people in the labs know more than their love of chemistry lets on about their work’s place in the world. Orr drives cancer patients to treatments for the American Cancer Society. Fang has seen breast cancer in the family. Lewis holds on to a CT scan of phase one’s Patient 23 from six years ago, four images of a drastically shrinking tumor that had him running down the hall in an oh-my-God-it-works moment that pushed everyone through some more 16-hour days. These are people who know what cancer patients need from their drug companies. They don’t need big annual earnings numbers. They don’t necessarily need record-breaking synthetic step totals. They don’t even need optimism, at least not for optimism’s sake.
They just need to hear a question, asked every day and by as many smart people as possible: How soon can we start climbing?
Innovation: Finding A Cure
Eisai in Andover Develops New Breast Cancer Drug
Michael Lewis discusses the Halaven molecule. Photo by Kevin Harkins.
As Michael Lewis sits at the table in his office at Eisai Inc. in Andover, looming nearby is a white board sketch of a mountain. Or what we’re calling a mountain. Eisai is a drug company, and Lewis is president of pharmaceutical science and technology. So the sketch is actually of a molecule. But Lewis is mercifully aware that he is talking very hard-core chemistry with very non-chemists, so out come the similes.
As he expounds on the Japanese-owned company’s recently approved, Andover-made breast cancer drug, Halaven, hoping against all reasonable odds to help his guests appreciate the mind-bending science and 18-year journey that produced a cancer fighter with more real potential than anything they’ve seen before, we are at various points baking a cake, building a skyscraper and captaining a supertanker. But scaling a mountain is the one he uses first, and the one that works best here. Because anyone who has ever looked up at a mountain knows that the second you do, you’re involuntarily assigned to one of two groups: The people who ask how soon we can start climbing, and everyone else.
Michael Lewis Ph.D.; Kenichi Nomoto, Ph.D.; Frank Fang Ph.D. Photo by Kevin Harkins.
Eisai’s Andover buildings are filled with the first group.
They had to be. In the quarter century since it was discovered in a sponge by a deep-sea diving Japanese chemist, the halichondrin B molecule has gotten attention for three main things: being from a sponge found by a deep-sea diving Japanese chemist (that is super cool; nobody disputes this), the wonderfully nasty things it does to cancer cells, and its legendarily complicated structure. Given a few millennia, nature can really do some amazing things. Even after famous (to chemists, anyway) Harvard professor Yoshito Kishi figured out how to make a simpler version in the lab, it remained a monster.
The notion of turning the halichondrin B molecule into a drug was a mountain so big nobody could see the top. More accurately, this thing frightened most of the pharmaceutical world into believing there might not even be a top. In an industry that’s practically all risk — the vast majority of drugs that make it to clinical trials die a costly death in phase one — this was too much of it. Everyone else stood at the bottom of the mountain, shook their heads and walked away, and they didn’t bother hiding the giggles as they passed the Eisai crazies lacing up their boots.
The FDA approved Eisai’s Halaven™ (eribulin mesylate) in November 2010. Courtesy Eisai, Inc.
“To be honest,” Lewis says, “most people outside the company thought we were lunatics.”
But lunatics make the best stories. Frank Fang is a chemist who worked on halichondrin B with Kishi at Harvard before moving down South for a while, only to end up being pulled inexorably back to the molecule in Andover like a salmon to a spawning site. John Orr had a job at a pharmaceutical giant where the molecules “weren’t all that interesting,” so he jumped to Eisai for the scientific thrill of figuring out how to manufacture what the FDA would eventually call the most synthetically complex drug it ever approved.
The drug was derived from the marine sponge Halichondria okadai. Courtesy Eisai, Inc.
Lunatics also lead you to more lunatics. The disarmingly polite Kenichi Nomoto will give you as much time as you need to understand his role in determining how the molecule worked in animals, but is more interested in giving credit to Bruce Littlefield. Littlefield was lured from Eisai by Harvard Medical School in 2009, but he personally did Eisai’s first experiment on the molecule 19 years ago, and given the chance to talk about it he will practically offer to drive to your house to do so. Not just because he believes it “has the potential to be the best cancer drug out there.” Not just because “no matter what I do for the rest of my career, I’ll never beat what we did in those years.” It’s also because he wants to talk about more Eisai-Andover guys like Melvin Yu and Murray Towle.
“Our strategic edge was that we knew nobody in their right mind would be trying to make something out of this,” says Littlefield, acknowledging that they probably wouldn’t have been allowed to try either if Eisai hadn’t been desperate to make a splash with its then-tiny U.S. operation. “We knew the competition would be zero, and we knew if we achieved this, it would blow everybody out of the water.”
Well … boom.
“This drug,” Orr explains, “is a 62-step synthesis. Companies don’t go much over seven, eight, nine steps.”
Jennifer Acker, principal researcher, Quality Control Chemistry. Photo by Kevin Harkins.
Once they knew they could produce enough for clinical trials in humans — those 62 steps take almost two years to finish — it needed to do something good, and the molecule delivered. In late-stage breast cancer patients who’d seen other chemotherapies already fail — the group it’s currently approved for — Halaven extended survival by an average of two to three months. If that doesn’t sound significant, take two notes: The first is that no drug had ever done that before; the second is that you should talk to a late-stage cancer patient about the concept of time.
But showing actual improvement in sick people, while super, comes right before showing the FDA you know what you’re doing. It’s not enough to prove you can do the whole 62-step dance reliably. You’ve got to prove you know what’s happening and why every step of the way, and help the feds understand it, too. Wondering why those simple molecules look so good? The paperwork alone is enough to crush a human soul.
Now having done it, they want to do it again, as much and as soon as possible. Trials are ongoing for earlier stage breast cancer, lung cancer and a slew of other applications. There’s quiet optimism inside Andover’s walls that we’re only seeing the beginning, and not-so-quiet expectations — perhaps better described as pressure — coming from Eisai’s global home in Tokyo. The CEO publicly declared it could become a billion-a-year earner if more trials go well.
Not that there’s anything like a guarantee with cancer. And if anyone needed a reminder of how tough the drug business is, Halaven’s FDA approval party in November was followed a few months later by Eisai’s announcement of 900 impending layoffs worldwide, thanks to losses from the patent expiring on its Alzheimer’s drug.
It helps, though, that the people in the labs know more than their love of chemistry lets on about their work’s place in the world. Orr drives cancer patients to treatments for the American Cancer Society. Fang has seen breast cancer in the family. Lewis holds on to a CT scan of phase one’s Patient 23 from six years ago, four images of a drastically shrinking tumor that had him running down the hall in an oh-my-God-it-works moment that pushed everyone through some more 16-hour days. These are people who know what cancer patients need from their drug companies. They don’t need big annual earnings numbers. They don’t necessarily need record-breaking synthetic step totals. They don’t even need optimism, at least not for optimism’s sake.
They just need to hear a question, asked every day and by as many smart people as possible: How soon can we start climbing?