Post by icemandios on Feb 16, 2022 20:17:45 GMT
February 16, 2022 02:02 PM ESTUpdated 02:13 PM Pharma
A new analyst report spotlights 3 more deaths, ARIA among Alzheimer's patients taking Aduhelm
John Carroll
Editor & Founder
A prominent Wall Street analyst is delving back into the agency’s adverse event database, identifying 3 additional deaths among patients taking the controversial Alzheimer’s drug Aduhelm — though he’s careful to add that there is no conclusive link between the drug and any deaths in this group so far.
Brian Abrahams
Brian Abrahams at RBC, who’s stirred up some controversy with an initial report of a patient death back in November, also ran some numbers on the reports of ARIA seen among these patients in an effort to tease out just how dangerous this drug may be when used in the real world, as opposed to to the carefully monitored clinical trials Biogen used to initially test its safety and efficacy. ARIA involves brain swelling and microbleeds that could threaten patients, though Biogen researchers have insisted that it’s a safety signal that can be monitored and treated in practice.
Exclusive: FDA probing death of Aduhelm patient as Biogen's Alzheimer's drug continues to stir controversy
These reports have raised a big issue for Biogen as it’s struggled to gain traction in the market with one of the most controversial therapies ever green-lighted by the FDA. Critics, and there’s a legion of them, have maintained that Biogen never came close to producing the kind of clear efficacy data that would warrant an accelerated approval. If the drug also proves a definite threat, it could push regulators to reconsider the approval.
Regardless of its presence on the market, though, payers have dug their heels in against covering the drug, and Medicare maintains, at least initially, that it will limit coverage to patients in certain clinical trials. Sales to date have been minuscule compared to initial projections.
Biogen investigates a death possibly linked to its controversial new Alzheimer's drug
Reports Abrahams:
We note deaths in this patient population and age group (pts were 86 and 74 y/o, with one unspecified) are not surprising; however, we also note there has been a limited amount of drug administered to date (we est. just 427 patients on therapy in 4Q21), so we believe this is a signal worth monitoring. For context, compared to the clinical trials, where there were 9 (0.4%) patient deaths during the over 2 years on the active arms, the real-world launch has seen a somewhat higher rate (0.7%); whether this is a real signal representative of high real-world risks in perhaps less fit and less well-monitored patients than in clinical trials, risks based on medical history, or just statistical noise remains unclear. One of the pts who died was an 86yo apparently with diabetes and heart disease which may have caused his death, though one was treated for a seizure (which could be associated with ARIA, though ARIA was not specified), and one was a 74yo with gait disturbance.
The rate of ARIA was generally low, with one event reported this quarter on commercial product (3 add’l listed for aducanumab), though we wonder whether this may reflect a lower rate of MRIs to access ARIA than a truly lower incidence vs. the clinical trial setting; it may also reflect the lack of clinical significance of ARIA. We also saw 3 seizures/epileptic events on commercial product, though seizures were also reported during the trials and no imbalances had been reported across arms. One additional signal worth monitoring is the risk of Ischemic stroke or transient attacks – of which there were 3 cases since commercial launch, though it is unclear what the baseline rate of attacks may be in this population.
As Abrahams has noted before, deaths and adverse events are gathered indiscriminately for the FAERS database. Other drugs have been tied to deaths and adverse events, yet maintained a clean bill of health at the agency, which accounts for patient populations that can be extraordinarily fragile, as in Alzheimer’s. But Abrahams has also offered his own opinion that the drug was likely a contributing factor in the first case. Both the FDA and Biogen report that they’ve been studying the first death, though Biogen took issue with Abrahams at the time, noting:
The RBC report only provides a partial view of the case. As we previously stated, the cause of death is unknown at this time. We know the 75-year-old clinical trial patient was admitted to the hospital with a seizure and diagnosed with cerebral edema thought to be ARIA-E. Following a prolonged hospitalization, the patient was being prepared for discharge when she deteriorated and was transferred to another facility. We have requested missing information, including brain imaging, from the critical last nine days of hospitalization.
A new analyst report spotlights 3 more deaths, ARIA among Alzheimer's patients taking Aduhelm
John Carroll
Editor & Founder
A prominent Wall Street analyst is delving back into the agency’s adverse event database, identifying 3 additional deaths among patients taking the controversial Alzheimer’s drug Aduhelm — though he’s careful to add that there is no conclusive link between the drug and any deaths in this group so far.
Brian Abrahams
Brian Abrahams at RBC, who’s stirred up some controversy with an initial report of a patient death back in November, also ran some numbers on the reports of ARIA seen among these patients in an effort to tease out just how dangerous this drug may be when used in the real world, as opposed to to the carefully monitored clinical trials Biogen used to initially test its safety and efficacy. ARIA involves brain swelling and microbleeds that could threaten patients, though Biogen researchers have insisted that it’s a safety signal that can be monitored and treated in practice.
Exclusive: FDA probing death of Aduhelm patient as Biogen's Alzheimer's drug continues to stir controversy
These reports have raised a big issue for Biogen as it’s struggled to gain traction in the market with one of the most controversial therapies ever green-lighted by the FDA. Critics, and there’s a legion of them, have maintained that Biogen never came close to producing the kind of clear efficacy data that would warrant an accelerated approval. If the drug also proves a definite threat, it could push regulators to reconsider the approval.
Regardless of its presence on the market, though, payers have dug their heels in against covering the drug, and Medicare maintains, at least initially, that it will limit coverage to patients in certain clinical trials. Sales to date have been minuscule compared to initial projections.
Biogen investigates a death possibly linked to its controversial new Alzheimer's drug
Reports Abrahams:
We note deaths in this patient population and age group (pts were 86 and 74 y/o, with one unspecified) are not surprising; however, we also note there has been a limited amount of drug administered to date (we est. just 427 patients on therapy in 4Q21), so we believe this is a signal worth monitoring. For context, compared to the clinical trials, where there were 9 (0.4%) patient deaths during the over 2 years on the active arms, the real-world launch has seen a somewhat higher rate (0.7%); whether this is a real signal representative of high real-world risks in perhaps less fit and less well-monitored patients than in clinical trials, risks based on medical history, or just statistical noise remains unclear. One of the pts who died was an 86yo apparently with diabetes and heart disease which may have caused his death, though one was treated for a seizure (which could be associated with ARIA, though ARIA was not specified), and one was a 74yo with gait disturbance.
The rate of ARIA was generally low, with one event reported this quarter on commercial product (3 add’l listed for aducanumab), though we wonder whether this may reflect a lower rate of MRIs to access ARIA than a truly lower incidence vs. the clinical trial setting; it may also reflect the lack of clinical significance of ARIA. We also saw 3 seizures/epileptic events on commercial product, though seizures were also reported during the trials and no imbalances had been reported across arms. One additional signal worth monitoring is the risk of Ischemic stroke or transient attacks – of which there were 3 cases since commercial launch, though it is unclear what the baseline rate of attacks may be in this population.
As Abrahams has noted before, deaths and adverse events are gathered indiscriminately for the FAERS database. Other drugs have been tied to deaths and adverse events, yet maintained a clean bill of health at the agency, which accounts for patient populations that can be extraordinarily fragile, as in Alzheimer’s. But Abrahams has also offered his own opinion that the drug was likely a contributing factor in the first case. Both the FDA and Biogen report that they’ve been studying the first death, though Biogen took issue with Abrahams at the time, noting:
The RBC report only provides a partial view of the case. As we previously stated, the cause of death is unknown at this time. We know the 75-year-old clinical trial patient was admitted to the hospital with a seizure and diagnosed with cerebral edema thought to be ARIA-E. Following a prolonged hospitalization, the patient was being prepared for discharge when she deteriorated and was transferred to another facility. We have requested missing information, including brain imaging, from the critical last nine days of hospitalization.