For an industry where progress is generally measured over decades or more, the state’s biotech world was rocked by two major developments in the span of just 16 hours this week.
Around 3 p.m. on Monday, the Food and Drug Administration announced it had approved a new combination drug by Boston-based Vertex Pharmaceuticals to treat cystic fibrosis — five months sooner than expected.
Then at 6:30 a.m. on Tuesday, Biogen said it would revive a medicine for early Alzheimer’s disease that it scrapped as a failure in March. The Cambridge firm plans to seek FDA approval based on a new analysis, although several stock analysts are deeply skeptical that Biogen will get the green light.
“We’re in a new era of biotech,” Alfred Sandrock, Biogen’s head of research and development and chief medical officer, said of both developments in a telephone interview. “We have better drug targets validated by human genetics.”
Many questions remain, particularly about Biogen’s stunning reversal. Still, the news involving two of the state’s biggest biotechs raised the hopes of families and
doctors desperate for drugs to treat the diseases.
Biogen’s announcement on Tuesday was the bigger bombshell. The firm has been working for years on the experimental drug aducanumab for Alzheimer’s. That form of dementia afflicts more than 5 million Americans, and no drugs significantly slow its ravages.
The hunt for an effective treatment has eluded some of the world’s biggest drug companies. According to an industry report, there were 146 failed attempts to develop medicines to treat and potentially prevent Alzheimer’s in the past two decades — and only four new drugs approved to treat symptoms.
On March 21, Biogen said it was abandoning tests on aducanumab based on the recommendations of an independent monitoring board entrusted to protect patients in the study.
Biogen and its Japanese partner Eisai said they halted two late-stage clinical trials after concluding that the compound was unlikely to benefit patients.
The news sent Biogen stock into a free fall, and the company lost a staggering $18 billion the day of the announcement. With the setback, Biogen joined the long list of drug firms that had struck out on Alzheimer’s treatments.
It also appeared to mark the demise of a series of experimental Alzheimer’s drugs that targeted a protein in the brain called beta amyloid, all of which had failed.
But Michel Vounatsos, Biogen’s CEO, and Sandrock said the aducanumab story didn’t end in March.
Biogen, in consultation with a team from the FDA, conducted a new analysis of a larger data set from the late-stage clinical trials that were halted, they said. The new analysis included additional data that became available after the prior analysis showed the study had no chance of success.
The new data showed that aducanumab was “pharmacologically and clinically active” in higher doses in reducing brain amyloid and in reducing clinical decline. Sandrock said the earlier data contained only about half the patients who had enrolled in the clinical trial and focused on people who had received smaller doses.
“We didn’t quite appreciate how important it was to get to a very high dose,” he said.
On Monday, a dozen Biogen scientists and statisticians and two representatives of Eisai met for two hours with eight FDA neurology officials at the agency’s Maryland headquarters, said Sandrock, who attended.
“We shared with them the entire data set, and we were told it was reasonable to submit” an application for approval of aducanumab, Sandrock said. Biogen expects to make the submission early next year.
Several analysts expressed deep skepticism that the FDA will OK the drug despite the new analysis.
Brian Skorney, an analyst with Baird, issued a report headlined “If You Torture the Data Long Enough, It Will Confess to Anything.”
“Biogen’s decision to file for regulatory for aducanumab in Alzheimer’s, after halting the study for futility, is understandable given the addressable market,” he wrote. “However we do not share their
enthusiasm for the interpretation of the results and believe approval would rely on regulators with minimal capacity for critical analysis.”
PiperJaffray analysts said in another report that aducanumab’s return “from the dead” was a “complete shocker” and that they weren’t sure what to make of the drug’s prospects.
However, Dr. Brent Forester, chief of geriatric psychiatry at McLean Hospital and a principal investigator in the aducanumab trial at his hospital, was delighted by the news.
Forester said six patients with early symptoms of Alzheimer’s received the drug. While it’s difficult to say whether it worked, he said, the patients seemed stable.
“There was never any indication that Biogen would pull the plug because it wasn’t working,” he said.
Debbie Rosenkrantz, a 66-year-old retired clinical social worker in Cambridge, said she took the medicine in the trial for about eight months. She felt it halted the decline in her memory.
“I actually felt like it was working, and then to be told that it wasn’t working was kind of disappointing to me,” she said. “This was a nice turnaround.”
The revival of aducanumab Tuesday sent Biogen’s stock up, and it closed up more than 26 percent on the Nasdaq. That helped the firm recoup some of the billions of dollars in value it lost when Biogen said it had pulled the plug on the compound.
Monday’s announcement about Vertex’s cystic fibrosis drug approval was widely expected — but the speed of the government ruling caught the industry by surprise. The FDA had set a goal of deciding whether to approve the drug by March 2020.
Vertex already has three cystic fibrosis drugs on the market. Trikafta, the new combination drug, is expected to benefit up to 90 percent of the 27,000 CF patients in the country, according to the FDA.
The FDA’s acting commissioner, Ned Sharpless, said after the drug won approval that the agency has been striving to speed the development of therapies for complex diseases.
Like Vertex’s other drugs for cystic fibrosis, Trikafta has a jaw-dropping list price: $311,000 a year.
Joseph J. O’Donnell, a Boston corporate tycoon whose son, Joey, died of cystic fibrosis in 1986 at the age of 12, was stunned to learn about the approval while on vacation.
O’Donnell has helped to raise hundreds of millions of dollars for the nonprofit Cystic Fibrosis Foundation, much of which has gone to Vertex for research.
He said he and his wife, Kathy, were on a cruise ship near Athens on Monday night when they heard the news in a phone call from their daughter, Kate O’Donnell.
The O’Donnells celebrated over dinner with six other couples with whom they took the cruise, all of them contributors to the fund.
“I knew this was going to happen sooner or later because all the results [of clinical trials] were so consistently good,’’ O’Donnell, 75, said in a phone interview. “But I never dreamed it would happen before the first of the year.”
Jonathan Saltzman can be reached at firstname.lastname@example.org