Precision Medicine and New Approaches Poised to Transform Psychiatry

The psychiatric field is experiencing heightened interest as new treatments for depression approach late-stage readouts, with many experts optimistic about the potential of precision medicine. In a market crowded with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), there remains a significant portion of the population still battling depression. In 2021, approximately 21 million adults in the U.S., or 8.3%, had at least one major depressive episode.

Amit Etkin, CEO of Alto Neuroscience, is optimistic about the future. He believes that new drug developments offer different mechanisms and targets, diverging from the traditional treatments available. "There’s no appetite for developing things that are similar to what we’ve had before," he said, highlighting the potential for a new class of antidepressants in the next five years.

Steve Butts, CEO of Arrivo BioVentures, echoed this sentiment, emphasizing the need for personalized medicine. He noted that while many medications exist, they haven't solved the issue of depression. The shift towards precision psychiatry is seen as crucial for both the industry and patients.

The success rate for psychiatric drugs is currently the lowest among non-oncology medications, with only a 6.2% chance of approval. Even successful drugs tend to have a small effect size. Etkin believes that precision medicine might change this, moving away from the traditional "all-comer" strategy in clinical trials. Historically, trials have included all patients diagnosed with a condition like major depressive disorder (MDD). A precision approach, however, would allow companies to understand the underlying biology of psychiatric disorders better and select patients expected to respond more favorably to the treatment.

Both Alto Neuroscience and Johnson & Johnson’s Janssen are adopting a precision approach to depression treatment. Janssen's trials are segmenting participants based on specific symptoms. For instance, its orexin antagonist, seltorexant, is being tested in MDD patients with insomnia, while aticaprant, a kappa-opioid receptor (KOR) antagonist, targets MDD patients with anhedonia. These studies are expected to yield results this year.

Alto Neuroscience is leveraging clinical biomarkers to select trial participants. The company examines cognitive tests or EEG measures to understand the underlying biology of each patient's brain. In December 2023, Alto reported positive results from its ALTO-300 trial, showing that patients with a specific EEG-based biomarker experienced a greater reduction in their depression scores compared to those without the biomarker. Another study in January 2023 found that 61% of biomarker-defined patients responded to ALTO-100, compared to only 33% without the biomarker.

Arrivo BioVentures is also developing a novel depression treatment, SP-624, which operates through an epigenetic mechanism. This treatment activates the SIRT6 enzyme, which is crucial for gene expression regulation, mitochondrial health, and DNA repair. A Phase I trial revealed that SP-624 alleviates depression symptoms more effectively in females, marking a significant step towards understanding the biological differences in how psychiatric disorders manifest between genders.

The neuropsychiatric field is attracting significant investment. Notable deals include Bristol Myers Squibb’s $14 billion acquisition of Karuna Therapeutics for its schizophrenia treatment, KarXT, and AbbVie's $8.7 billion acquisition of Cerevel Therapeutics for its antipsychotic, emraclidine. These investments underscore the growing confidence in novel psychiatric treatments.

On the depression front, Neurocrine Biosciences has shown promising Phase II data for a Takeda-partnered asset targeting the AMPA receptor, designed for patients unresponsive to current antidepressants. KOR antagonists, such as Janssen’s aticaprant and Neumora Therapeutics’ navacaprant, are also in advanced trials, highlighting the industry's focus on new mechanisms of action.

The move towards precision psychiatry and novel mechanisms not only offers the potential for improved patient outcomes but also stands a better chance for reimbursement. Insurers are more likely to cover innovative treatments, ensuring that the significant time and investment in drug development are not wasted.

In conclusion, the psychiatric field is on the brink of a potential revolution, driven by precision medicine and novel therapeutic mechanisms. This shift could significantly enhance the efficacy of treatments and offer new hope to millions suffering from depression.