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The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.
It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.
In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”
The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.
Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
A New POV
The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.
In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element.
In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.
“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted.
The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).
“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”
However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals.
A Faster Pathway to Approval
The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”
Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures.
Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.
The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.
The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added.
Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.
The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.”
“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.
A version of this article appeared on Medscape.com.
The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.
It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.
In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”
The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.
Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
A New POV
The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.
In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element.
In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.
“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted.
The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).
“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”
However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals.
A Faster Pathway to Approval
The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”
Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures.
Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.
The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.
The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added.
Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.
The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.”
“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.
A version of this article appeared on Medscape.com.
The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.
It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.
In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”
The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.
Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
A New POV
The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.
In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element.
In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.
“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted.
The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).
“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”
However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals.
A Faster Pathway to Approval
The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”
Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures.
Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.
The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.
The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added.
Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.
The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.”
“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.
A version of this article appeared on Medscape.com.