Alzheimer's is currently the most common dementia disease, with an estimated 30 million individuals living with the disease. Unfortunately, effective treatments are lacking despite researchers having worked in the field for the past hundred years, and there are still several pieces to put into this complex neurodegenerative puzzle.
Great potential for effective treatment
The cost of Alzheimer's drugs currently amounts to approximately USD 6 billion annually, despite the fact that current options have poor treatment effects and are associated with a number of side effects. A drug with better treatment effects therefore has high potential sales and revenue opportunities. The analysis company Global Data estimates that annual global sales will reach $13 billion by 2028 for disease-modifying drugs for Alzheimer's disease.
Defeat in the EU for Biogen
Given the pressing medical need and steady research progress, expectations have been high when new drug candidates have been presented. Unfortunately, all hopes have ultimately been dashed when the desired significant clinical improvements have not been achieved.
In recent years, research has made progress and hopes were high for the pharmaceutical giant in particular. Biogen candidate aducanumab (Aduhelm). The drug is a monoclonal antibody that binds to the protein amyloid beta (Aβ) in the patient's brain. The hypothesis is that the protein creates harmful plaques in the brain and by binding to amyloid beta, aducanumab can clear the plaque.
At the end of December 2021, the European Medicines Agency recommended EMA:'s Human Medicine Committee CHMP Aduhelm was denied marketing authorization in Europe. The committee said that while the candidate reduces amyloid beta (Aβ) in the brain, this effect had not been linked to clinical improvement in patients. In addition, Biogen's Phase III clinical trials showed worrying side effects such as brain swelling and bleeding, and the treatment was not effective in adults with early-stage disease.
However, the last word has not yet been said as Biogen will request a new review from the EMA.
A conditional and controversial approval in the US
In the United States, American FDA a different assessment. In early June, Biogen received a so-called Accelerated Approval from FDA, which is a regulatory shortcut that aims to approve treatments early even if knowledge about treatment effects and side effects is incomplete.
Read more about the decision in BioStock's article from June 2021. here.
Biogen is now conducting a Phase IV study to study the drug's efficacy and side effects in a larger study group as a requirement for obtaining Accelerated Approval. As recently as December 20, 2021, a large number of Alzheimer's researchers published demands that the drug should be immediately withdrawn. Biogen, which on December 20 halved the price of Aduhelm after criticism regarding its high pricing, thus risks meeting the same fate as all other developers in recent years.
Shotgun approach misses its target
The only type of treatment that has so far shown a positive effect in clinical studies is passive immunotherapy where the drug candidate binds to aggregated amyloid beta, i.e. both to insoluble plaques and to oligomers. Biogen's aducanumab has a higher affinity for aggregated amyloid beta than for the unaggregated forms, but does not show particularly high selectivity for the oligomeric forms compared to the plaque. In other words, the problem is that this and other plaque-reducing treatments attack forms that are not particularly harmful to varying degrees with what could be called a shotgun approach.
Alzinova's more accurate alternative
Swedish Alzinova offers a new solution for how Alzheimer's disease could be slowed and prevented. The company's patented AβCC peptide technology enables the development of disease-modifying treatments that, according to Alzinova, target the harmful amyloid beta oligomers that are central to the onset and progression of the disease with great accuracy.
Alzinova's hypothesis is that specifically targeting the harmful amyloid beta oligomers is important both to achieve a good effect and to avoid serious side effects. The hope, which Alzinova wants to confirm clinically, is that a higher specificity against oligomers will show a better clinical effect than other alternatives.
The Alzheimer's vaccine ALZ-101
Alzinova's main candidate ALZ-101 is an active therapeutic oligomer-specific vaccine with best-in-classpotential whose specificity and administration method are believed to bring several advantages over competitors, including better efficacy with fewer side effects, as well as an attractive long-acting treatment option that can be handled in primary care. The vaccination causes the body to generate its own antibodies specifically targeted against neurotoxic amyloid beta oligomers in the brain, thereby neutralizing the harmful substances and protecting the brain's synapses. Preclinical studies showed a 25 percent increase in synapses in mice. In two completely independent collaborations with research groups at University of Gothenburg and Amsterdam Medical Centers It has also been demonstrated that the company's products have a unique ability to specifically neutralize what causes the toxic effect in the brain, despite the fact that these oligomer-specific antibodies completely lack the ability to bind unaggregated amyloid-beta and plaques.
ALZ-101 has successfully passed the preclinical development phase and at the end of October, Alzinova announced that the first patient had been recruited to a Phase Ib study in Finland.
New innovations will be required
The attention surrounding Biogen shows the great potential for successful treatment in the Alzheimer's field.
Alzinova certainly has much to prove, but if the promising preclinical data are validated in clinical studies, the company's strategy of the benefits of a more specific approach will also be confirmed. If the hypothesis of a better treatment effect and a better safety profile can be supported, there are the conditions for success in the notoriously difficult-to-treat disease Alzheimer's.
Also read BioStock's interview with Alzinova's CEO Kristina Torfgard, published on December 20, 2021 here.
The content of BioStock's news and analysis is independent, but BioStock's operations are to some extent financed by companies in the industry. This post refers to a company from which BioStock has received funding.