20.05.2022 | Insight

The challenges facing new drug treatment in Alzheimer’s Disease

By Mary Kangley

Alzheimer’s disease (AD) is the most common form of dementia causing gradual cognitive impairment and memory loss, often beginning with an individual’s short term memory. There are currently around 900K people living with the disease in the UK and an estimated 54 million people with any form of dementia globally. There is no known cure for the disease, but there are medical treatments available for a variety of symptoms, including memory loss, confusion and other behavioural effects. There is presently a large amount of ongoing research into the cause and treatment of AD, with a selection of new pharmaceutical products seeking regulatory approval and marketing authorisation.

As a result of the prevalence of the disease and the ever-advancing research, healthcare professionals (HCPs) across the globe use social media to raise awareness of symptoms, offer supporting advice and discuss up-and-coming treatments in the field. CREATION Pinpoint® identified almost 70K English language posts about Alzheimer’s over the past year posted by 14K HCPs worldwide. The most significant driver in the conversation was the controversial FDA approval of Biogen’s Aduhelm (aducanumab), the first novel therapy approved for the disease since 2003.

Throughout the year, a number of events spiked the interest and conversation of HCPs as the new product was scrutinised following its FDA approval.

Graph showing aduhelm approval spikes HCP interest

Aduhlem’s journey to FDA approval

Prior to Aduhelm’s approval, it had had a number of failed and discontinued trials on account of safety concerns. Only a few months later, Biogen filed for regulatory approval with the backing of new analysis and a larger dataset. The presentation of this data at #CTAD19 was met with more questions than answers as HCPs remained cautiously optimistic of the impact this treatment would have for patients. 

Before the approval there was already a divided sentiment, made more prominent by the views of significant organisations and advocacy groups. While the American Geriatrics Society urged the FDA not to approve the drug, the Alzheimer’s Association promoted aducanumab in a campaign called #moretime.

June 7th: Approval day

The week of the accelerated approval of Aduhelm saw a peak of over 5K HCP tweets dissecting and deliberating the news. HCPs were left confused by the decision since there hadn’t been “enough evidence to approve Aduhelm”. 

HCPs called it a “dark day” as the approval came despite failed trials and disapproval from the FDA’s own scientific advisory panel. This contradiction by the advisory panel proved to be significant evidence to validate HCP reactions as a STAT News article recording the resignation of a panel member was shared over 100 times. The evidence appeared multi-faceted as HCPs cited the insufficient efficacy data, unreasonably high costs and worrying safety statistics.

July 13th: FDA response

A month after the news of Aduhelm’s approval came to light, an article was published in JAMA Internal Medicine from the FDA’s Center for Drug Evaluation and Research (CDER) giving their perspective on the regulatory decision. The piece was introduced to “discuss the complexities of the data supporting the aducanumab application and the rationale for the FDA’s decision to grant it accelerated approval.”

A Family Medicine physician from New Haven, CT, Reshma Ramachandran, published a Twitter thread breaking down the key points of the article, warning her network not to read it unless they “want their blood to boil”.

Dr Ramachandran cited discrepancies across phase I-III trials, suboptimal secondary endpoints and “most infuriating and saddening” a false hope for patients who have wondered when they’ll be able to receive the supposedly ineffective treatment.

One of the authors of the article, the director of the FDA’s Office of Neuroscience Billy Dunn, appeared central to the events of this approval and one HCP asked in a Twitter poll whether disciplinary action was warranted against him.

Another HCP in Italy, Matteo Cesari, shared the FDA viewpoint to his network on Twitter, suggesting that “subjective feelings” had been prioritised over the data, which should not be the case.

The response from HCPs on Twitter was rather unanimous as they considered all the data and surrounding events and conversations, often calling out specific individuals for endorsing the decision. A psychiatrist in the UK, Robert Howard, wondered whether there was a parallel Twitter world with “joyful celebrations”.

January 11th: Medicare access restriction

After months of unfolding controversy, Medicare, the US federal health coverage program, announced they would be restricting access to Aduhelm for only patients in clinical trials (and only those randomised controlled trials approved by the agency). 

Before this announcement, many hospital systems (not to mention individual HCPs) made clear they would not be prescribing nor administering the drug. US Cardiologist C. Michael Gibson shared this rejection by Cleveland Clinic and Mount Sinai hailing it “one of the starkest signs of concern” over the approval. He used a Twitter poll to gauge reactions; the majority of the 141 respondents agreed with the decision due to lack of efficacy:

By definition, Medicare only covers products that are “reasonable and necessary”, differently to the requirements of an FDA approval when a product must be “safe and effective”. Safety concerns spiked when an AD patient died from a side effect that could be linked to Aduhelm called “amyloid-related imaging abnormalities” (ARIA).

The decision for Medicare to restrict access came after a myriad of conversations about the price tag attached to Aduhelm. Biogen had initially priced the drug at $56,000 for an average dose, but later slashed the price in half to around $28,000. Dr Henry Rosenberg used this price cut to explore the wider issue of drug pricing, calling for a bottom-up approach.

A physician in Toronto, David Juurlink, brought the scenario to real life when he postulated that he wouldn’t prescribe such an expensive, side effect prone intravenous drug to an AD patient with mild symptoms.

A holistic perspective

Zooming out on the conversation, the pricing issue extended to expose areas of need that could be improved with additional financial investment. Geriatrician Aroonsiri Sangarlangkarn stipulated that a better way to spend $56,000 for an AD patient would be to pay a more adequate wage to caregivers.

World Alzheimer’s Day saw over 1,000 HCP posts on September 21st with an increased dialogue about recognising AD symptoms and ramping up support for those affected by the disease. Many HCPs used the day to break down the different facets of AD from diagnosis to treatment.

Ruminda H. Gunaratne wrote a tweetorial in which he answered the question of how to treat AD, making it clear there is no cure, but cholinesterase inhibitors such as donepezil may have some benefit.

Two other drugs that are in development for AD are donanemab and gantenerumab from Lilly and Roche respectively. Donanemab has earned positive phase II results while gantenerumab has received FDA breakthrough status despite missing its primary endpoint in phase II/III trial. HCPs are wary and keeping a close eye on data as these two new drugs are “amyloid clearing” just as Aduhelm.

What HCPs Think

Aduhelm’s approval has shown how impactful HCP opinions are and a successful approval does not equate to a successful launch. Despite a wish for an AD cure, HCPs will not sacrifice their obligation for sound safety and efficacy data before approving a treatment for their own prescribing. The unravelling of events was able to be tracked in HCP online conversation, revealing where there were needs and opportunities to support patients in a tangible and effective way. CREATION.co provides HCP insights and tracking services that can keep a finger on the pulse of drug approvals and launches, in order to understand what HCPs think.

This article was first published on Pharmaceutical Market Europe (PME).

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Meet the Author

Mary Kangley

Mary is passionate about telling stories with data from online healthcare conversations. Her work is guided by a background in human and cyber-psychology providing a curiosity to understand what HCPs think.

As a keen music fan, Mary’s greatest pride is her Spotify playlists that are continually growing as she makes new discoveries.

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