Biogen on Thursday mounted a vigorous defense of its controversial Alzheimer’s drug, Aduhelm, with the company’s head of research and development releasing an open letter to the Alzheimer’s community that took direct aim at critics of approval.
Al Sandrock, the R&D chief and an architect of many of Biogen’s successes, wrote that the purpose of the letter was to correct “misinformation” about the drug.
“Unfortunately, Aduhelm’s approval has been the subject of extensive misinformation and misunderstanding,” Sandrock wrote. “It is normal for scientists and clinicians to discuss data from experiments and clinical trials, to debate, and to disagree, on the interpretation of data. That is how science advances and we welcome these discussions. Recently, however, there has been a turn outside the boundaries of legitimate scientific deliberation.”
The company’s chief executive, Michel Vounatsos, echoed those comments on a call with investors. “I want to be clear that Biogen stands behind the integrity of the review process,” Vounatsos said. He said he understood concerns about the drug’s $56,000 price, and promised to make sure that patients would be able to receive it.
Biogen on Thursday also reported better-than-expected second-quarter sales of $2.78 billion, a decrease of 25% according to a year ago, in part due to a 24% drop in sales of the company’s flagship multiple sclerosis drugs. The company earned $448 million in the quarter. Earnings per share excluding unusual items were $5.68, 25% above the forecasts of investment analysts polled by FactSet.
Sales of Aduhelm, which was approved June 7, were $2 million.
In his letter, Sandrock commented on much of the furor that has enveloped the Alzheimer’s drug, which critics say should not have been approved because they believe its clinical trials don’t show that the drug benefits patients. A panel of experts from the Food and Drug Administration had previously voted that the drug should not be cleared. Several FDA panelists resigned in protest over the approval. There has also been pushback on the drug’s price.
Last month, STAT reported about unusual meetings between the FDA and Biogen and the company’s efforts to use back channels in fighting for the approval of the drug. Janet Woodcock, the FDA’s acting commissioner, has called the independent Office of the Inspector General to investigate how agency staff interacted with Biogen.
“We welcome a formal review into the interactions between the FDA and Biogen on the path to the approval of aducanumab,” Sandrock wrote. “A better understanding of the facts is good for everyone involved to assure confidence in both the therapy and the process by which it was approved as we prioritize the issues that affect patients.”
He went on to address several points that he cast as misinformation. First, he emphasized, the accelerated approval pathway that was used to approve Aduhelm is not new, and has been used more than 250 times, implying that the use of Aduhlem was not unusual. However, he did not address more specific criticisms, such as that the FDA previously did not view the removal of amyloid plaque, which is found in the brains of Alzheimer’s patients, as “reasonably likely” to show a benefit, the standard for accelerated approval. Sandrock wrote that he believes Aduhelm’s approval will be “further established,” but did not provide a timeline for the completion of a follow-up study.
Scientists disagree about whether the removal of amyloid plaque is likely to mean that a medicine is effective. In his letter, Sandrock addressed this, too.
“Several people have stated that all previously studied anti-amyloid antibodies clear amyloid from the brain but have failed as a class to demonstrate benefit,” he wrote. “This is factually incorrect.” These earlier antibodies, Sandrock emphasized, “do not clear amyloid from the brain.” However, the FDA used a review of previous antibody studies in patients that had reduction in brain amyloid as part of its justification of approval.
The studies that led to Aduhelm’s approval were initially stopped because the company thought they could not succeed, only for Biogen to later find that one appeared successful and the second didn’t. Sandrock wrote that critics said that the results are “post hoc” — a scientific term that means the results were analyzed after the fact and are therefore likely invalid. He emphasized that the studies used their predetermined measures for success.
However, the FDA’s statistical reviewers, who opposed the drug’s approval, wrote repeatedly in memos released by the agency that some of Biogen’s analyses, including those it used to argue that its failed study was also supportive of efficacy, were post hoc.
Sandrock also defended the close working relationship between the FDA and Biogen.
“It is important to recognize that collaboration between industry and regulatory agencies is common, appropriate and beneficial,” he wrote. “That was exemplified at its best with the COVID-19 vaccine development. As a doctor, a scientist and the Head of Research and Development at Biogen, I believe scientists at regulatory agencies and drug manufacturers must work together in an effort to defeat other devastating public health threats.”
Sandrock acknowledged that the data about Aduhelm are “complex” and that the drug did not follow “a conventional path.” He wrote: “But the road to innovation is rarely straightforward, and Aduhelm is not an exception.”
“The letter is no substitute for a report of the trial data in the peer reviewed academic literature,” said Samuel Gandy, a professor at Mount Sinai Hospital in New York. “Physicians are on their own to work out whether and if so how to use this drug. The label offers almost zero guidance. The least the company could do is publish the results of the trials so that all the stakeholders could see not only all the data but all the same data.”
In a striking exchange on the call, Jay Olson, an investment analyst at Oppenheimer, asked why the media had mounted such an “assault” on Aduhelm.
“It seems like ever since March of 2019, Biogen’s been the target of constant assault from the media and other groups, which obviously intensified on June 7, when Aduhelm was approved,” Olson said. “What do you suppose it is about Alzheimer’s disease that causes the media to react so negatively to a drug that could actually help patients and their families and not treat them with the same respect that is rightly shown to victims of other diseases like cancer?”
“You are absolutely right in your question and your description of what we are exposed to,” Vounatsos replied. “But we are not the ones suffering the most. It is still the early days in the launch. It is still the beginning. And whatever the motives of the controversy are, the ones that are potentially misled, confused, denied help are the patients.”
He then argued that past experience in areas such as HIV indicates that this kind of early approval can lead to more competition, and, later on, bigger gains for patients.
One of the FDA panelists who resigned, Aaron Kesselheim, the director of a program that studies regulation at Brigham & Women’s Hospital, wrote in his resignation letter that part of his objection to the approval was the “debatable premise” that removing amyloid is likely to help Alzheimer’s patients.
Analysts have focused on another set of data: whether health insurance plans and the government’s Medicare program will pay for the drug. Medicare is taking an unusual step, called a National Coverage Determination, to decide whether and for whom to pay for the medicine.
Biogen said that 900 sites will be ready to offer Aduhelm infusions — the drug must be given intravenously — soon after approval. Of those 900, the company said that 35% have either completed a positive review by a pharmacy and therapeutics committee, which determines whether a drug will be given, or have said that one will not be required. Two large hospitals, the Cleveland Clinic and the Mount Sinai Medical Center, have said they will not be offering Aduhelm. The company also said it expects Medicare Advantage plans, a form of Medicare built around private insurance, will cover the drug until the coverage determination process is complete.
This story has been updated with outside comment, more details from Biogen’s call with investors and on insurance coverage for Aduhelm.