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, Aduhelms’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% decrease 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 pre-determined 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.”
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