Cerebral and Alto Neuroscience Launch At-Home Depression Trial

The Rise of Decentralized Clinical Trials

Even prior to the widespread adoption of remote work, education, and research spurred by the pandemic, decentralized clinical trials were anticipated to become more prevalent. Currently, this trend is gaining significant momentum.

This week marked a collaboration between Alto Neuroscience, a precision psychiatry startup, and Cerebral, a provider of online mental health services. They announced the initiation of a decentralized Phase 2 clinical trial focused on ALTO-300, Alto Neuroscience’s investigational drug for depression.

Trial Design and Participant Recruitment

The majority of the study procedures will be conducted within the participants’ own homes. Approximately 200 volunteers will be recruited from Cerebral’s existing user base.

These individuals will be selected based on their current experience with depression and a lack of positive response to previously prescribed treatments. Alto Neuroscience will not only administer the new drug but also seek to confirm the effectiveness of its drug development strategy.

This strategy centers around utilizing patient biomarkers to forecast which patients are most likely to benefit from a particular medication, and conversely, those who are unlikely to respond.

A Synergistic Partnership

David Mou, Cerebral’s Chief Medical Officer, explained to TechCrunch that the concept of comprehensive patient profiling to identify responsive subgroups before substantial clinical trial investment was logically sound.

“The notion of thoroughly characterizing a patient population to determine which segments derive genuine benefit from a drug, before committing a billion dollars to clinical trials, was intuitively appealing, yet remained largely unimplemented,” Mou stated.

He further emphasized the complementary nature of the partnership, stating, “It was a remarkably fitting alliance. We possessed the resources they required, and I am confident that their vision represents the most practical path forward.”

Decentralized clinical trials offer a potentially more efficient and patient-centric approach to drug development.

The Growing Appeal of Decentralized Clinical Trials

The precise definition of a decentralized clinical trial isn't uniform, but fundamentally, it involves delivering healthcare services to patients directly, either through virtual means or by utilizing mobile healthcare professionals. Crucially, data collection also occurs in the patient’s environment, rather than solely within traditional study centers.

Shifting clinical trials to the patient’s location presents a viable solution to significant challenges currently hindering the clinical trial process, primarily by reducing the burden on participants. A substantial 70% of individuals participating in clinical trials reside more than two hours from a designated study site, for example.

Patient enrollment frequently leads to trial terminations, with approximately 80% of clinical trials experiencing delays in patient recruitment. Furthermore, industry professionals believe that a decentralized approach could potentially enhance the diversity and accessibility of pharmaceutical research.

While not the inaugural instance of a decentralized clinical trial, this particular study emerges at a pivotal moment for the field.

Prior to the global pandemic, only 38% of pharmaceutical companies and contract research organizations (CROs) indicated to McKinsey that decentralized clinical trials would constitute a significant component of their overall strategies.

However, a subsequent McKinsey survey conducted in 2020 revealed a complete shift in perspective, with 100% of the same organizations anticipating a substantial role for decentralized trials moving forward.

Insights from this Clinical Trial

This investigation holds the potential to illuminate the reliability of remotely gathered data, the FDA's stance on such information, and whether decentralized clinical trials effectively address longstanding challenges inherent in traditional, site-based studies. 

The acquisition of comprehensive data is particularly crucial for Alto Neuroscience’s pharmaceutical development strategy. The company’s foundation rests on creating distinct, biomarker-defined profiles of individuals diagnosed with mental health conditions, utilizing EEG measurements alongside mood and emotional assessments. 

“Our focus is on the development of novel therapeutics for a range of psychiatric disorders, with a key emphasis on identifying the optimal patient population through brain-based testing and biomarkers,” explained Amit Etkin, founder and CEO of Alto Neuroscience, in an interview with TechCrunch. 

“Consequently, a central tenet of our work is ensuring our biomarkers accurately pinpoint, in a broadly applicable manner, those patients most likely to benefit from our treatments.” 

Cerebral emerged as a compelling partner for Alto Neuroscience’s forthcoming trial due to several factors. Notably, the company demonstrated the ability to rapidly identify a patient cohort meeting the trial’s specific criteria: “We were able to identify these 200 patients within a single hour,” Mou stated. 

However, the primary advantage lay in Cerebral’s pre-existing extensive data collection on patients and their healthcare providers – indicating a capacity to gather the high-caliber data required by Alto Neuroscience. This includes data pertaining to individuals experiencing severe depressive symptoms (a demographic often underserved by wellness-focused applications). 

For instance, Cerebral patients routinely complete questionnaires detailing their symptoms and emotional state. The company also maintains records of physician prescribing practices, potentially offering valuable insights into treatment efficacy. 

“Our commitment to delivering high-quality care necessitated the creation of a robust data infrastructure, enabling us to possess a more comprehensive understanding of our patients and clinicians than any other mental health provider currently,” Mou added. 

A remaining consideration centers on how the FDA will assess data obtained through decentralized, and potentially remote, methods. This evaluation process is currently evolving. In April, the agency mandated that oncology decentralized trials differentiate between in-person and remotely collected data within their datasets. 

This trial could serve as a valuable benchmark. Alto Neuroscience is presently conducting two comparable clinical trials of ALTO-300: one in collaboration with Cerebral, and a second utilizing the conventional site-based approach. 

Etkin clarified that the objective extends beyond merely evaluating the efficacy of ALTO-300. It aims to validate the entire concept of a decentralized, precision psychiatry clinical trial. 

“A significant aspect of our endeavor is to demonstrate to the FDA that the data obtained through a decentralized methodology is comparable in quality to that gathered in a traditional, site-based setting,” Etkin explained. 

Furthermore, there is indication that this trial addresses obstacles associated with traditional clinical trials – such as difficulties in patient recruitment. However, it is not without limitations. The participants in the Cerebral trial, for example, are concentrated in New York, Dallas, and Atlanta, not representative of populations residing far from major medical facilities. 

“Does it fully resolve the issue of representation? Not entirely,” Mou acknowledged. “However, I believe it yields a more accurate participant group: The likelihood of genuine depression among these individuals is considerably higher than when recruiting through conventional brick-and-mortar clinics.” 

Transitioning from Research to Market Availability

The founders emphasized the potential of decentralized trials to facilitate the eventual market release of new drugs. Mou highlighted Cerebral’s capability to efficiently distribute a medication to suitable patients following regulatory approval.

From Alto Neuroscience’s viewpoint, Cerebral represents a valuable pathway for integrating mental health biomarkers into routine clinical practice – a challenge that has historically hindered accurate diagnosis of mental health disorders.

Traditionally, mental health assessments have relied on observed behaviors, rather than objective medical evaluations. However, ongoing research, alongside efforts from companies like Alto Neuroscience, aims to shift the focus towards diagnosis grounded in verified biomarkers.

“A collaborative partner such as Cerebral would be perfectly positioned to implement our biomarkers, upon approval, within a clinical setting, due to the highly organized and meticulously documented nature of their patient care.”

Initial results from the ongoing trial are anticipated by the close of 2022.