Summary
Large and Innovative Pipeline
The active Alzheimers Disease (AD) pipeline is populated with 583 products, with a highly diverse range of molecular targets. GBI Research analysis revealed a high degree of innovation in this indication, with 46% of the pipeline being first-in-class products, acting on over 40 first-in-class molecular targets. In addition, the pipeline is characterized by the strong presence of therapies that target multiple components implicated in the amyloid cascade, several molecular targets of which are known to trigger familial AD. Given that the currently approved therapies for AD are limited to acetylcholinesterase inhibitors and glutamate receptor antagonists, the pipeline offers a broad range of treatment options that may possess disease-modifying properties. However, evaluation of the Preclinical and clinical evidence for their therapeutic potential reveals that the novelty of the molecular target is not sufficient to effectively reduce the rate of AD progression in human patients.
Disease-Modifying Therapies Show Promise in Early-Stage Development
Programs undergoing Preclinical development exhibit diverse disease-modifying mechanisms of action, and many represent strong alternatives to targets with a direct role in the amyloid and tau processes due to their roles in promoting neuronal survival and plasticity, a process critical to memory and cognition. Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) are considered promising targets in AD, primarily due to their potency in exhibiting significant neuroprotective effects in Preclinical studies. Members of the caspase-mediated apoptotic cascade also show therapeutic potential, as early investigations have revealed an ability to modulate molecular mechanisms underlying synaptic plasticity in animal models, which translates into amelioration of behavioral deficits. Thus, growing insights into disease-causing processes in AD are being translated into a growing population of innovative therapeutic targets, as reflected in the highly innovative pipeline.
The merits of novel molecular targets depend largely on the body of Preclinical evidence underpinning their relevance to AD pathology. Many endpoints in Preclinical investigations focus on amelioration of amyloid burden and tau pathology, as well as cognitive performance in animal model systems. Based on these assessment criteria, it appears that programs targeting the amyloid cascade, tau pathology, and the promotion of neuronal survival and plasticity all demonstrate promising efficacy profiles. Other first-in-class targets that are less directly aligned to these three processes may not be able to confer disease-modifying properties and therefore lack clinical and commercial potential.
Active Deals Landscape with Numerous Investment Opportunities
The AD deals landscape has been highly active over the past eight years, with 83 licensing agreements and 103 co-development deals. Overall, non-first-in-class programs tend to have lower valuations than first-in-class programs across all stages of drug development, which highlights their commercial attractiveness, even in early-stage development. Although first-in-class programs are associated with greater risk, they have more potential to revolutionize or improve therapeutic options, meaning that identifying promising first-in-class compounds early in development offers the greatest potential commercial benefit to pharmaceutical companies.
With 153 first-in-class products that are currently in development having not yet been involved in a licensing or co-development deal, there are numerous opportunities for in-licensing or co-development in this indication.
Scope
The report covers and includes -
- A brief introduct
