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Third member of prestigious FDA panel resigns over approval of Biogen’s Alzheimer’s drug



A sign for the Food and Drug Administration is seen outside of the headquarters on July 20, 2020 in White Oak, Maryland.
Sarah Silbiger | Getty Images

A third member of a key Food and Drug Administration advisory panel has resigned over the agency’s controversial decision to approve Biogen‘s new Alzheimer’s drug, Aduhelm, CNBC has learned.

Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School, said the agency’s decision on Biogen “was probably the worst drug approval decision in recent U.S. history,” according to his resignation letter obtained by CNBC.

“At the last minute, the agency switched its review to the Accelerated Approval pathway based on the debatable premise that the drug’s effect on brain amyloid was likely to help patients with Alzheimer’s disease,” he wrote in resigning from the FDA’s Peripheral and Central Nervous System Advisory Committee.

Shares of Biogen surged 38% Monday after the FDA approved the biotech company’s drug, the first medication cleared by U.S. regulators to slow cognitive decline in people living with Alzheimer’s and the first new medicine for the disease in nearly two decades.

The agency’s decision was a departure from its from the advice of its independent panel of outside experts, who unexpectedly declined to endorse the drug last fall, citing unconvincing data. At the time, the panel also criticized agency staff for what it called an overly positive review of the data.

This is a developing story. Please check back for updates.

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Blue Origin auctions seat on first spaceflight with Jeff Bezos for $28 million



A New Shepard rocket launches on a test flight.
Blue Origin

Jeff Bezos‘ space venture Blue Origin auctioned off a seat on its upcoming first crewed spaceflight on Saturday for $28 million.

The winning bidder, whose name wasn’t released, will fly to the edge of space with the Amazon founder and his brother Mark on Blue Origin’s New Shepard rocket scheduled to launch on July 20. The company will reveal the name of the auction winner “in the weeks following.”

Bidding opened at $4.8 million but accelerated quickly above $20 million within the first few minutes of the auction. The auction’s proceeds will be donated to Blue Origin’s education-focused nonprofit Club for the Future.

New Shepard, a rocket that carries a capsule to an altitude of over 340,000 feet, has flown more than a dozen successful test flights without passengers, including one in April at the company’s facility in the Texas desert. The autonomous system is designed to carry up to six people. The capsule has massive windows to give passengers a view of the earth below during about three minutes in zero gravity, before returning to Earth.

Blue Origin director of astronaut and orbital sales Ariane Cornell said during that New Shepard’s first passenger flight will carry a crew of four, with the final person also to be announced later.

New Shepard launches vertically, and both the rocket and capsule are reusable. The boosters land vertically on a concrete pad at the company’s facility in Van Horn, Texas, while the capsules land using a set of parachutes.

The interior of the latest New Shepard capsule
Blue Origin

Bezos founded Blue Origin in 2000 and still owns the company, funding it through share sales of his Amazon stock.

July 20 also marks the 52nd anniversary of the Apollo 11 moon landing.

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Auto insurance rates rise, but insurers could still qet squeezed by higher costs ahead



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An employee at a used auto dealership treads water as he checks on vehicles they are moving out of the rising waters from two days of heavy rain in Lexington, Miss., Thursday, June 10, 2021.
Rogelio V. Solis | AP

Despite recent increases in auto insurance rates, the market is still soft, according to Elyse Greenspan, a managing director at Wells Fargo.

“The increase sequentially was very modest,” Greenspan said in an interview. “The reason why there was a strong increase year over year is because the premium base in May 2020, was impacted by all the refunds.”

As the amount of driving consumers did fell, auto insurers refunded $14 billion in premiums last year, according to the Insurance Information Institute. Rates continued to stagnate, or even decline, through the first quarter.

However, the most recent consumer price index data showed the auto insurance index up 16.9% in May, following a 6.4% rise in April — the first increases since March 2020.

Auto insurers are facing a number of challenges as the econonmy reopens. Workers are returning to offices and vaccinations are prompting many people to take summer vacations. Government data from March, the most current statistics available, show driving up 19%.

The result of people returning to pre-Covid driving levels means the rate of car accidents will rise, according to Michel Leonard, III vice-president.

If this year’s trend follows last year, the accidents may also be more severe. Though the number of driving hours plummeted by 13% last year, fatalities climbed 7%, according to the National Highway Transportation Safety Administration. Experts blame a higher incidence of speeding, impaired driving and distracted driving for the increase.

Also, Leonard said, many drivers are out of practice, especially at parking or navigating through traffic.

More accidents mean more claims — and those claims are expected to be more expensive for insurers to pay because repair costs are rising.

The CPI data has shown month after month of gains for auto repairs. The 2.8% increase in May was a bit slower than in the pace of prior months. (Repair costs climbed 3.5% in April and March, 3.1% in February and 3.5% in January.) And wait times are also longer thanks to chip shortages, supply chain disruptions and a labor crunch.

Still, not all insurers are raising rates. In a Wells Fargo analysis, Greenspan said the Hartford and Allstate raised rates in May, but Travelers, Progressive and State Farm saw rates decline. Geico increased rates in April, but didn’t file rate changes for May, he said.

“It’s still a good environment for consumers who are purchasing auto insurance,” Greenspan said.

She anticipates the environment will remain tough for auto insurers through fall as commuters return to work, students head back to school and people who took mass transit before the pandemic opt to switch to driving themselves.

“There’s just a lot of headwinds from a severity and a frequency perspective,” she said.

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Biogen Alzheimer’s drug and the battle over dementia treatment of the future



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Aduhelm by Biogen
Source: Biogen

The FDA’s approval of Biogen‘s Alzheimer’s drug Aduhelm was a landmark moment in the life of Dr. Paul Aisen. The director of the Alzheimer’s Therapeutic Research Institute at USC has spent the past three decades focused on treating the neurodegenerative disease, and in recent years helped shepherd this particular drug through the various phases of clinical trials.

But sitting in his sun-drenched office in San Diego in early June, he felt slightly confounded by the manner in which the Food and Drug Administration early June approved its use on an “accelerated” basis, which is usually reserved for cancer medications. This meant its clinical benefits were considered likely, but approval for long-term use would be subject to more extensive study in a fourth phase of trials.

Highlighting the “unusual nature” of the regulator’s green light, given that an advisory board of experts had strongly, and publicly, opposed the approval, Aisen, who works as a paid consultant to Biogen, insists there were still “a lot of questions that I have — that do not yet have answers.”

Three members of the FDA panel overseeing research have resigned since the approval this week, including Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School, who said in a letter the agency’s decision on Biogen “was probably the worst drug approval decision in recent U.S. history.”

Last November, in an 8-1 vote, that panel said Biogen’s late-stage study didn’t provide “strong evidence” showing that aducanumab effectively treated Alzheimer’s; two other panelists said it the data was “uncertain.”

While Aisen considers Aduhelm an “effective treatment” for a disease that affects millions of Americans, he also has concerns about the FDA ruling’s implications for the panoply of other potential treatment options that are in late-stage development.

One immediate challenge facing other teams working on a wider Alzheimer’s drug pipeline, he said in a recent video call, would be to retain participants in ongoing trials, let alone attract new ones.

“In most cases,” he explained, many Alzheimer’s sufferers will drop out of other drug studies to pursue treatment with the newly approved Aduhelm. Their departures would make trial data for those alternative drugs less useful, even though the drugs in question might one day prove safer, more effective, or more appropriate for different stages of the disease’s progression. But perhaps perversely, he still considers Aduhelm’s approval “a boost towards those efforts — a strong boost.”

Over 6 million Americans suffer from Alzheimer’s

In recent years, some major drug companies abandoned efforts to research brain diseases, including Pfizer and Boehringer Ingelheim in 2018 — in fact, Biogen had given up on Aduhelm at one point during the clinical trials in 2019 before reversing its decision— after decades of failure in search of a breakthrough.

The controversy surrounding the Biogen drug, including its potential cost, comes against a landscape of massive, unmet need for dementia treatment and a disease that costs the U.S. as much as $259 billion annually. More than 6 million Americans have Alzheimer’s or another form of dementia, according to estimates from the Alzheimer’s Association, and by 2050 that number could reach over 12 million people at a cost of $1 trillion annually.

That is why some dementia drug experts are focusing on the renewed attention and fresh financing rather than the potential negatives from the Biogen approval, according to Dr. Jeffrey Cummings, a neurologist at the University of Nevada, Las Vegas, who publishes an annual review of the Alzheimer’s drug development pipeline. His research consistently showed the drug-failure rate at 99.6 percent before the Biogen approval, a stark contrast to the 1 out of every 5 cancer drugs (20%) that are successful.

Cummings says any negative side effect for other drug trials in the short term would be “overcome, if anything, by the increased interest that companies and venture capital and biotech has, once they see that there is a way to get an approval for a particular disease.”

In recent history, The National Institutes of Health spent two to three times more on heart disease and cancer research than on dementia, while lack of qualified participants for clinical trials also slowed progress.

Next in the dementia drug pipeline

For the handful of other developmental Alzheimer’s drugs hoping to clear those same regulatory hurdles and prove their efficacy — Eli Lilly‘s donanemab, Roche’s gantenerumab and Eisei’s lecanemab among them — there may be a silver lining to ceding first-mover advantage to Aduhelm.

After decades of expensive but thus far largely fruitless research trials, the CEO of pharma giant Eli Lilly, David Ricks, said his firm was “getting closer and closer to the goal” after a positive set of Phase Two results for its offering, donanemab.

Speaking at CNBC’s Healthy Returns Summit in May, a month before the FDA’s approval for rival Biogen’s Aduhelm, he said his team felt “good about the probability of success,” and said he wanted to explore an “accelerated” route too, using what he called “adaptative pathways at the FDA to consider looking at data sooner” that “should be applied in a serious and widespread condition like Alzheimer’s.”

However, he acknowledged that recruitment for the next phase of trials required a significantly larger cohort of participants, and given that it would last 18 months, he did not expect a new approved product before late 2023 at the earliest.

Several experts told CNBC the Biogen drug’s unique threshold for regulatory approval, with treatment potential seeming to trump uncertain real-world benefits, could reinvigorate efforts by competitors like Lilly, who are focused on developing drugs that rely on relatively similar techniques.

Aduhelm’s own clinical trial data had shown the drug successfully targets and clears out clusters of a specific type of protein that are believed by many researchers to be responsible for Alzheimer’s. But it offered insufficient evidence to prove the drug provides patients with cognitive benefits.

Debate over targeting beta amyloid formations

Known among scientists as aducanumab, it works by offering an array of identical antibodies that are cloned from white blood cells. These antibodies are chosen for their targeting abilities, since they can identify specific proteins, called beta amyloids, that have constructed particular formations in the body.

There is extensive evidence suggesting that these beta amyloid formations, also known as “pathological aggregates” or “plaques,” are a major driver of Alzheimer’s disease, though the exact causal mechanisms are still not fully understood, according to Christian Pike of USC’s Leonard Davis School of Gerontology. Nonetheless, he says the antibodies can help prevent these plaques from forming, before directing other particles to break them apart, a process that’s clearly identifiable in before-and-after neural imaging.

For an analogy, it may be helpful to think of the beta amyloid proteins as young people walking around a city over the course of the day, where the city is the human body, and the day is a human lifespan. In certain cities, as afternoon turns into evening, individual young people start to congregate, and some of those congregations can turn toxic, and begin to cause problems. The antibodies delivered by Aduhelm act like law enforcement officers, arriving on the scene, identifying troublesome gatherings, surrounding them, separating them, then ordering bystanders to make the young people disperse.

“If you say ‘Well hey, the FDA is buying into this general concept,'” said Pike in a phone call, “if we can remove beta amyloid from the brains of persons that are affected by the disease, even with limited evidence of cognitive benefits,” he continued, “there might be a variety of different therapies that would qualify under these types of criteria.”

The long line of past failures from within the Alzheimer’s pipeline that targeted beta amyloid will continue to weigh on optimism, until conclusive proof is generated — something this week’s controversy over the first new Alzheimer’s drug approved in decades indicates has not been done yet.

“What we’re going to find out from the use of this drug one way or the other is whether or not the amyloid clearing hypothesis is correct,” says USC health economist Darius Lakdawalla, who argues the continued trialing of Biogen’s drug will prove useful to that confirmatory effort.

“If it is correct, then I think it opens the door for a lot of innovation, a lot of drug candidates that are going to try to clear amyloid in the future pursuit of that hypothesis.”

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