CAMBRIDGE, Mass. — Biogen (BIIB) thought it had developed a treatment for Lou Gehrig’s disease, a devastating illness that leaves patients trapped in their own atrophying bodies until, inevitably, they die. After early clinical studies yielded encouraging results a few years ago, the biotech company took a home-run swing and launched a huge final-stage trial to prove the drug worked.
When the study failed, scientists broke into tears at the news, crushed that what seemed like a godsend for patients was no better than placebo. And then they went out drinking.
“We took the whole team out, like 30 people, to one of the top restaurants in Boston,” recalled Steve Holtzman, Biogen’s executive vice president of development at the time. “We bought champagne, really fine wine, and we had an Irish funeral.”
Such heavy-hearted celebrations are common in biotech, where failures far outnumber successes. Just this summer, giants like Bristol-Myers Squibb, AstraZeneca (AZN), and Celgene (CELG) have run into costly setbacks with drugs in the pipeline. And smaller players including Seres Therapeutics (MCRB), Tokai Pharmaceuticals, and Tobira Therapeutics have endured clinical failures that call into question their long-term survival.
Companies churn through thousands of molecules before hitting upon one safe and effective enough to test in humans. And even those chosen few have but a 10 percent chance at ever making it onto a pharmacist’s shelf, according to data from Biomedtracker, a research service that keeps tabs on the industry.
Drug companies use those dismal rates of success to defend the escalating cost of new treatments. Each approved therapy, they argue, stands on the shoulders of a thousand lesser compounds and should be priced accordingly.
But down among the scientific rank and file, the rate of attrition in drug development is just part of the job. Scientists slog through years of research to get a slot in biotech, then often spend an entire career toiling in labs without once touching a project that matures into an approved drug. It can be emotionally taxing, as Biogen’s investigators learned, leading many companies to commemorate the many noble hypotheses that come up short.
And thus failures are often feted.
“You celebrate the achievement of getting an answer,” said Matthew Kennedy, Merck’s director of neuroscience research, even if that answer is a resounding “no.”
It’s morale maintenance, in part, but toasting a big idea that fell flat also helps encourage scientists to chase the next breakthrough, said Seng Cheng, head of rare disease research at Sanofi’s Genzyme division.
And it’s good business. Publicly traded biotech companies put about a quarter of their revenues into research and development, amounting to a roughly $35 billion investment last year, according to a recent report from Nature Biotechnology. Cutting the cord on a once-promising program saves companies from throwing good money after bad.
“If these failures are found quickly, they’re often rewarded as handsomely as successes,” Seng said.
But choosing when to kill a program is rarely easy. If you ask scientists, “there’s always a glimmer of hope,” said John Butler, CEO of the anemia-focused biotech Akebia Therapeutics (AKBA). A change in chemistry, a pivot in patient recruitment — rarely do researchers perceive a wall that can’t be circumnavigated with a little more time and money.
“Two things are always true: Drugs that deserve to die refuse to die, and yet for over 90 percent of successful drugs, they failed once or more along the way but for a champion refusing to let them die,” said Holtzman, who is now CEO of Cambridge’s Decibel Therapeutics.
That makes for the greatest conundrum in leading a biotech company, Holtzman said. No one wants to mothball what could be the next major advance in cancer, but if you blow your research budget on a thrice-failed drug, you might lose your job.
The trick is balancing passion and objectivity, according to Merck’s Kennedy. Drug hunters must at once be able to go full-bore into their projects and be clear-eyed about their likely failures, he said.
With the ever-present specter of an eventual bad result, companies take pains to reward the little victories along the path of drug development.
Small trophies, plaques, and inscribed pill bottles dot the desks at Merck’s neuroscience operation in Boston, handed out in honor of steps along the path. At Moderna (MRNA) Therapeutics in Cambridge, scientists received ceremonial — but empty — vials of the company’s first drug candidate to commemorate its inaugural clinical trial, now underway.
And when that 1-in-10 shot comes through and a drug wins approval, companies reach a little deeper into their morale budgets. Two years ago, Genzyme got the Food and Drug Administration’s blessing to market a drug for a rare disorder known as Gaucher disease, capping a 15-year process. And so the chemists who discovered it gathered around an oblong table, invited to a slice of company-provided cake. Then they went back to work.