Why Hope Endures For An Alzheimer’s Treatment — And Biogen Could Be First




When Kris Bakowski was diagnosed with Alzheimer’s disease in 2002, the Georgia resident felt relieved to finally put a name to the fog that was slowly enveloping her brain, even if there was no viable Alzheimer’s treatment.

For months, she would forget her own phone number. She had trouble with colleagues’ names. Mapping out her route home from work became a chore. One day she found herself alone at the mall without any recollection where she was or how she got there.

Biopharma companies believe they might be able to help soon. Analysts say Biogen (BIIB) could be first to crack the code on a disease-modifying Alzheimer’s treatment that slows the disease’s progression. Indeed, Biogen and Tokyo-based Eisai announced late Thursday that Phase 2 tests on their Alzheimer’s drug slowed progression of the disease after 18 months. The news sent Biogen stock soaring by more than 23% at one point Friday.

Novartis (NVS), Roche (RHHBY), Amgen (AMGN) and others also are developing potential Alzheimer’s drugs, along with a number of development-stage biotech companies.

Victory is not certain, though. A number of Big Pharma companies, including Merck (MRK), Eli Lilly (LLY) and Johnson & Johnson (JNJ), have been down this road and abandoned planned Alzheimer’s treatments. But at least one expert sees success in the next decade, which wouldn’t come too soon for Bakowski and other Alzheimer’s patients.

Bakowski, now 62, has been blogging about her Alzheimer’s experience for 15 years. In a blog post for the Alzheimer’s Association, she describes the eight months of testing that led to her diagnosis and subsequent relief. She’s hopeful for a cure in her son’s lifetime, but her family isn’t so optimistic.

«My husband likened it to the Titanic — that the ship was sinking, and he and my son were going to survive and I wasn’t,» she wrote. «My son reflected that it was like his mother was on death row, but innocent of the crime.»

Alzheimer’s Treatment Market

The potential Alzheimer’s market is massive. An estimated 5.7 million Americans are living with Alzheimer’s or other forms of dementia. Without a way to intervene, the Alzheimer’s Association expects the cost of caring for people with these diseases to hit $1.1 trillion by 2050, in today’s dollars. That would be up from an estimated $277 billion in 2018.

But, like Bakowski, many experts are hopeful.

Privately held Proclara Biosciences is among a cadre of biotech companies aiming to develop an Alzheimer’s treatment. Chief Medical Officer David Michelson calls the field «pretty vibrant.»

Michelson, who has held positions at Merck and Lilly, says the steady drumbeat of «bad news» in Alzheimer’s treatments reflects not so much a failure to affect their specific targets in the brain but issues such as side effects in specific tests. He recently spoke during a webinar hosted by Endpoints News.

«There’s a lot of really tremendous work that’s ongoing and it’s enabling new approaches that are becoming possible and generating promising new targets,» he said. «I am actually very hopeful and optimistic about what the next five to 10 years hold for research in Alzheimer’s.»

Biogen Drug: Possible Timeline

Several drugs have been approved in the U.S. to treat dementia of the Alzheimer’s type, including Aricept from Eisai and Namenda from Allergan (AGN). Both treat the symptoms of Alzheimer’s disease. Neither can cure the disease.

Elliot Goldstein, chief executive of ProMIS Neurosciences, can count these types of treatment on one hand. None of them slow the progression of the disease, he told Investor’s Business Daily. ProMIS is also working on an Alzheimer’s treatment. It trades on the Toronto Stock Exchange for under 1 and doesn’t have any sales or earnings yet. Goldstein previously worked at Novartis, which is also developing Alzheimer’s drugs.



Biogen’s strongest hope is a drug now dubbed aducanumab. Goldstein predicts the drug will come to market in 2020.

«Aducanumab has a high potential of approval because it has showed a small improvement on decline» of patients into Alzheimer’s symptoms, he said.

Biogen did not respond to a request for comment for this article.

In total, Biogen has six potential Alzheimer’s treatments in its pipeline. Aducanumab is farthest along, with a late-stage study likely to have data in 2019 or 2020, analysts say.

Biogen and Eisai’s Thursday announcement involved another drug known as BAN2401. Tests involved 856 patients diagnosed with early Alzheimer’s. The companies said the drug, an antibody, achieved «statistical significance on key predefined endpoints» that evaluated effectiveness at 18 months. Biogen stock jumped 19.6% to close at 357.48 but had surged to an intraday high of 367.89 for a gain of 23.1% at one point.

Still, it’s a messy field. Biogen stock plunged 6.6% on Valentine’s Day this year after it added 510 new patients to an ongoing study of aducanumab. That move caught investors off-guard. Also that week, Merck scrapped a late-stage Alzheimer’s treatment study as the risks looked likely to outweigh benefits.

«It can be a volatile area,» Canaccord analyst Sumant Kulkarni told Investor’s Business Daily. «There have been very spectacular failures in the past. There’s a component of the investor who thinks, ‘What if the next one works?’ That can help from a stock point of view.»

Then again, he said, «Nothing else has worked in the past.»

Alzheimer’s Treatment Approaches

The trouble in Alzheimer’s treatment research is that scientists aren’t exactly sure what causes the disease. One prevailing theory ties the disease to the buildup of toxic plaque in the brain. That happens when a protein called beta-amyloid structurally changes. Beta-amyloid is sticky and clumps together, becoming plaque.

Pharmaceutical companies are looking at two approaches to beta-amyloid that essentially boil down to either removing it or preventing it. BACE inhibitors work to prevent the buildup, while monoclonal antibodies — like Biogen’s aducanumab — aim to remove it.

ProMIS’ Goldstein notes adverse events also must be sidestepped. Some Alzheimer’s treatments come with a side effect known as amyloid-related imaging abnormalities, or ARIA. This refers to swelling in the brain. Goldstein says ProMIS’ Alzheimer’s treatment, set to begin clinical studies in 2019, doesn’t cause that.

But Mizuho analyst Salim Syed says it’s possible to help patients get past ARIA. A common idiom of the industry is, «If you don’t get ARIA, are you really treating the plaque?» he told IBD.

Then, there’s the trouble of determining whether a study is designed well, Proclara’s Michelson says. First, evidence must show the drug engaged the intended target, like beta-amyloid. Second, patients must be proven to actually have Alzheimer’s. Third, the study must be big and of appropriate duration.

«It turns out when you look back across history, there aren’t that many studies and that many drugs that have been studied in a way that really fulfills all three of these elements,» he said.

Failed Alzheimer’s Drug Studies

He argues that only two studies have hit all three design goals. They are Merck’s now-failed BACE inhibitor known as verubecestat and Biogen’s aducanumab.

In February, Merck scrapped a study of its Alzheimer’s treatment in patients with prodromal, or very early-stage, Alzheimer’s disease. A year earlier, it said the same drug had «virtually no chance of finding a positive effect» in patients with mild or moderate forms of the disease.

Meanwhile, the field is thinning. J&J stopped a midstage test of a BACE inhibitor in a group of patients in May because of liver safety concerns. In January, Pfizer (PFE) stopped all research in Alzheimer’s and Parkinson’s diseases.

Lilly’s Alzheimer’s treatment failure in late 2016 was acutely painful for the company. Its monoclonal antibody called solanezumab lost out in three late-stage studies. The last study was in patients with a mild form of Alzheimer’s.

Alzheimer’s Treatment Drug Combos

ProMIS’ Alzheimer’s treatment binds to several toxic misfolded proteins causing Alzheimer’s, Goldstein says. It functions on the theory that there are other targets in Alzheimer’s disease outside of beta-amyloid. Some drugs are also testing the theory that tangles of a protein called tau could be the root cause.

Privately held United Neurosciences hopes to come in with a vaccine for Alzheimer’s. The goal is to use the drug as both a treatment for early Alzheimer’s and as a preventive measure. Physicians must administer the drug before «it’s too late to rescue the brain,» United Neurosciences Chief Medical Officer Ajay Verma told Investor’s Business Daily.

Verma’s background is at Biogen, where he directed the development of drugs, including aducanumab. Before that, he was at Merck and Novartis.

Verma expects aducanumab to get approval. Several sell-side analysts model around a 35% likelihood that aducanumab can appease the Food and Drug Administration.

But Verma sees a possibility that aducanumab could be expensive, since it would be the first treatment to slow the progression of Alzheimer’s disease. «I think the challenge is, will it be a solution or just for the rich?» he said.

Verma ultimately expects the solution to treating Alzheimer’s disease to lie in combinations of drugs. That’s been key in treating cancer, HIV, cardiovascular disease, metabolic disease and high cholesterol, he says.

‘Tricky’ Alzheimer’s Research Complexities

Without intervention, the number of Alzheimer’s patients will triple by 2050, James Hendrix said in Endpoints News’ webinar. Hendrix is the director of global science initiatives for the Alzheimer’s Association.

«We need better therapies and we need them sooner rather than later,» Hendrix said.

But Alzheimer’s treatment studies are tricky, United Neurosciences’ Verma says. A barrier between the blood and the brain makes getting a drug to the brain difficult. Plus, animal models aren’t particularly predictive, and studies must run for long periods of time.

Further complicating matters, science isn’t sure which stage is the best to treat.

Those reasons are at the center of a 0.5% approval rate from the FDA for Alzheimer’s treatments, according to a 2015 paper presented by Hendrix. The industry average is 4.1%.

Research is improving, though, Hendrix says. Scientists are aware of the potential impact of beta-amyloid and tau, as well as a number of approaches targeting different stages. In the end, it could be enough for an Alzheimer’s treatment to just delay the beginning of the disease by several years, he says.

«It might be possible to delay the onset for us to die of something else,» he said.




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