Breakthrough drugs aren't always driven by novel biological targets. Major successes like Humira or GLP-1s often succeeded through a superior modality (a humanized antibody) or a contrarian bet on a market (obesity). This shows that business and technical execution can be more critical than being the first to discover a biological mechanism.

Novo Nordisk ran a nearly 4,000-patient Phase 3 Alzheimer's trial despite publicly stating it had a low probability of success. This strategy consumes valuable patient resources, raising ethical questions about whether a smaller, definitive Phase 2 study would have been a more responsible approach for the broader research ecosystem.

Alzheimer's can be understood as a vascular disease rooted in nitric oxide deficiency. This decline impairs blood flow, glucose uptake, and inflammation regulation in the brain. Therefore, strategies to restore nitric oxide address the physiological root causes of the disease, not just the symptoms like plaque buildup.

The NIH's cancellation of mRNA research is a profound strategic error. The technology's key advantage is speed, which is critical not only for future pandemics but also for personalized cancer treatments. These therapies must be developed for individual patients quickly, making mRNA the most promising platform.

Abivax's drug has a novel, not fully understood mechanism (miR-124). However, analysts believe strong clinical data across thousands of patients can trump this ambiguity for doctors and regulators, citing historical precedents like Revlimid for drugs that gained approval despite unclear biological pathways.

Unlike sedatives, DORA-class sleep aids (Dual Orexin Receptor Antagonists) work by inhibiting wakefulness, creating more natural sleep architecture. Research suggests this may improve the brain's ability to clear beta-amyloid and tau proteins linked to Alzheimer's disease, offering a potential preventative strategy.

Beyond tackling fatal diseases to increase lifespan, a new wave of biotech innovation focuses on "health span"—the period of life lived in high quality. This includes developing treatments for conditions often dismissed as aging, such as frailty, vision loss, and hearing decline, aiming to improve wellbeing in later decades.

Novo Nordisk's large semaglutide Alzheimer's trial failure highlights a critical design flaw: launching a massive study without first using smaller trials to validate mechanistic biomarkers and confirm central nervous system penetration. This serves as a cautionary tale for all CNS drug developers.

Unlike sedatives like Ambien, a new class of medication (DORAs) works by dialing down the brain's wakefulness chemical (orexin). This allows for naturalistic sleep that is functionally beneficial, proven to increase the brain's cleansing of beta amyloid and tau protein, which are linked to Alzheimer's disease.