Alkermes Initiates Phase 2 Study of ALKS 7290 as Adjunctive Treatment for Major Depressive Disorder
Alkermes plc has announced the initiation of a Phase 2 clinical study evaluating ALKS 7290, an investigational orexin 2 receptor (OX2R) agonist, as an adjunctive treatment for adults with major depressive disorder (MDD). The study will assess the safety, tolerability and preliminary efficacy of ALKS 7290 when administered alongside standard antidepressant therapy. The clinical development program represents another step in Alkermes’ efforts to advance orexin-based therapies for neuropsychiatric conditions with significant unmet medical needs.
ALKS 7290 is an investigational small-molecule OX2R agonist being developed by Alkermes for multiple neuropsychiatric indications, including attention-deficit hyperactivity disorder (ADHD) and the adjunctive treatment of MDD. Through its research into orexin biology, the company is exploring the potential of activating the orexin system to influence neural pathways involved in wakefulness, attention, cognition and mood regulation.
The newly initiated Phase 2 study will investigate whether ALKS 7290 can provide additional therapeutic benefits when combined with existing antidepressant medications in adults who continue to experience symptoms of depression. The trial will include participants with and without excessive daytime sleepiness, allowing researchers to evaluate the investigational treatment across different clinical presentations of MDD.
The study is designed as a randomized, double-blind, placebo-controlled clinical trial and is expected to enroll approximately 180 adult participants diagnosed with MDD. Participants will be assigned to receive either ALKS 7290 or placebo in combination with their existing antidepressant therapy for six weeks. The primary objective is to evaluate the safety and tolerability of the investigational drug, while secondary assessments will examine changes in depressive symptom severity and overall clinical status.
The initiation of this study strengthens Alkermes’ clinical pipeline and supports its broader strategy of developing medicines that target the orexin system across multiple neuropsychiatric disorders.
Exploring Orexin Biology in Neuropsychiatric Disorders
Orexin biology has emerged as an important area of scientific investigation because of its role in regulating several physiological and neurological processes. The orexin system consists of neuropeptides and their corresponding receptors that help regulate wakefulness, arousal and other functions associated with the central nervous system.
Orexin signaling is mediated primarily through two receptors: orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). These receptors are involved in coordinating neural activity associated with alertness, sleep-wake regulation and other brain functions.
OX2R is particularly relevant to the regulation of wakefulness and arousal. Researchers are also investigating the broader connections between orexin signaling and neural circuits associated with attention, cognition, motivation and mood.
These biological relationships have created opportunities to explore orexin receptor agonists as potential treatments for conditions involving disruptions in these neurological functions.
Alkermes is investigating whether activating OX2R could offer a differentiated therapeutic approach to neuropsychiatric disorders. Rather than focusing exclusively on neurotransmitter pathways commonly targeted by existing psychiatric medications, the company’s research is examining the potential of the orexin system as an additional mechanism for addressing symptoms associated with conditions such as ADHD and MDD.
In major depressive disorder, symptoms can extend beyond persistent sadness and may include reduced motivation, impaired concentration, fatigue, changes in sleep patterns and difficulties with everyday functioning. Some patients continue to experience substantial symptoms despite receiving antidepressant treatment.
The biological complexity of depression suggests that targeting additional neurological pathways could potentially provide new treatment opportunities. By investigating OX2R activation as an adjunctive approach, Alkermes aims to determine whether ALKS 7290 can complement the effects of established antidepressant medications.
The Phase 2 clinical study will provide an opportunity to generate initial clinical evidence regarding the potential role of orexin receptor activation in managing depressive symptoms.
ALKS 7290 Advances Into Phase 2 Development for Depression
ALKS 7290 is an investigational OX2R agonist that forms part of Alkermes’ broader orexin-based research and development strategy.
The candidate is being evaluated for its potential to address neurological and psychiatric conditions through activation of the orexin 2 receptor. Its development for ADHD and adjunctive MDD treatment reflects the company’s interest in exploring the role of orexin signaling across different disorders involving attention, alertness and other aspects of brain function.
The newly initiated Phase 2 study will specifically evaluate ALKS 7290 as an additional therapy for adults with MDD who are receiving standard antidepressant treatment.
Adjunctive treatment refers to the use of an additional medicine alongside an existing therapy to potentially improve treatment outcomes. In depression, some patients may not achieve adequate symptom improvement with their initial antidepressant medication. Others may experience persistent symptoms despite appropriate treatment.
Consequently, investigating additional therapeutic mechanisms is an important area of clinical research.
The trial will assess whether ALKS 7290, when administered with antidepressant therapy (ADT), can demonstrate an acceptable safety and tolerability profile and provide evidence of potential improvement in depressive symptoms.
The study will also include participants with and without excessive daytime sleepiness. This aspect of the trial may help researchers better understand the potential relationship between orexin system activation and different symptom profiles among individuals with MDD.
By examining a broader group of patients, Alkermes intends to evaluate the investigational therapy in a population that reflects the clinical variability associated with major depressive disorder.
Details of the Randomized, Double-Blind Phase 2 Trial
The Phase 2 clinical study is designed as a randomized, double-blind, placebo-controlled trial. These clinical research methods are widely used to evaluate investigational medicines and help reduce potential bias when assessing treatment outcomes.
Approximately 180 adult participants diagnosed with major depressive disorder are expected to enroll in the study.
Eligible participants will be randomized into treatment groups and receive either ALKS 7290 or placebo alongside their existing antidepressant therapy. The treatment period will last six weeks.
The double-blind design means that neither participants nor the investigators directly responsible for evaluating them will know which study treatment has been assigned during the blinded portion of the trial. The placebo-controlled approach will allow researchers to compare outcomes between participants receiving ALKS 7290 in addition to antidepressants and those receiving placebo with antidepressants.
The study includes primary and secondary objectives.
Primary objective: Safety and tolerability
The primary objective is to evaluate the safety and tolerability of ALKS 7290 when administered as an adjunctive treatment to standard antidepressant medications.
Researchers will assess the treatment’s safety profile during the six-week study period. This evaluation will help determine how well participants tolerate ALKS 7290 in combination with their existing antidepressant regimens.
Safety and tolerability are essential considerations in the development of new psychiatric medicines, particularly when an investigational treatment is intended to be administered alongside existing medications.
The findings will provide important information to guide decisions about the continued clinical development of ALKS 7290 in MDD.
Secondary objective: Changes in depressive symptom severity
The secondary objective is to determine whether participants receiving ALKS 7290 in combination with antidepressant therapy experience improvements in depressive symptoms compared with participants receiving placebo alongside antidepressant treatment.
The study will evaluate changes from baseline using two established clinical assessment instruments:
- Montgomery–Åsberg Depression Rating Scale (MADRS): A clinical assessment tool used to measure the severity of depressive symptoms and evaluate changes in depression over time.
- Clinical Global Impressions-Severity Scale (CGI-S): A clinician-rated instrument used to assess the overall severity of a patient’s illness.
Both measures will be used to assess clinical outcomes at Week 6.
The MADRS evaluation will provide a structured assessment of depressive symptom severity, while the CGI-S will offer an overall clinical assessment of the participant’s condition.
Comparing changes in these measures between the ALKS 7290 and placebo groups will help researchers determine whether the investigational therapy demonstrates preliminary evidence of therapeutic benefit when added to standard antidepressants.
Although the primary focus of the study is safety and tolerability, the secondary efficacy assessments will provide important information about the potential clinical activity of ALKS 7290.
Addressing Unmet Needs in Major Depressive Disorder
Major depressive disorder is a common and potentially debilitating psychiatric condition that can affect emotional well-being, cognitive functioning, physical health and everyday activities.
People living with MDD may experience persistent low mood, loss of interest in previously enjoyable activities, fatigue, sleep disturbances, changes in appetite, impaired concentration and reduced motivation. The severity and combination of symptoms can vary considerably between individuals.
Although several antidepressant medications are available, treatment response is not consistent across all patients. Some individuals experience meaningful improvements with their initial treatment, while others may require medication adjustments, alternative therapies or additional treatment approaches.
For patients who do not achieve sufficient symptom control, adjunctive treatment strategies represent an important area of clinical research.
Alkermes is investigating whether ALKS 7290 could provide a complementary mechanism of action by targeting OX2R. The company’s scientific rationale is based on the role of orexin signaling in neural circuits involved in wakefulness, attention, cognition and mood.
The inclusion of participants with and without excessive daytime sleepiness is particularly relevant to the study’s design. Sleep-related symptoms and daytime functioning can vary among individuals with depression, and the trial may help researchers explore whether the investigational treatment has potential across these different patient characteristics.
However, the clinical effectiveness of ALKS 7290 in MDD has not yet been established. The Phase 2 study is intended to generate early clinical evidence and determine whether further development is warranted.
Alkermes Highlights the Potential of Orexin-Based Therapies
Craig Hopkinson, MD (MBChB), chief medical officer and executive vice president of Research & Development at Alkermes, highlighted the scientific importance of orexin biology and the company’s objectives for the newly initiated clinical study.
“Orexin biology represents a compelling area of scientific exploration in neuropsychiatry, given its central role in regulating wakefulness and its broad connections to neural circuits relevant to attention, cognition and mood,” Hopkinson said.
He explained that the Phase 2 proof-of-concept study is intended to assess whether activating the orexin system could provide a new approach to addressing symptoms of major depressive disorder.
Hopkinson also emphasized that the initiation of the study represents another important milestone in the company’s efforts to advance its portfolio of OX2R agonists.
According to him, the clinical development program reflects Alkermes’ commitment to maintaining a leadership position in the development of orexin-based therapies across multiple neuropsychiatric indications.
The company’s strategy involves exploring the therapeutic potential of orexin receptor activation in different conditions, rather than restricting its research to a single disease area.
The advancement of ALKS 7290 into Phase 2 development for MDD adds another clinical opportunity to this strategy and provides a platform for evaluating the compound’s potential in a new patient population.
Clinical Development Strategy and Future Opportunities
The initiation of the MDD study represents an important step in Alkermes’ ongoing efforts to expand its research into orexin-based medicines.
ALKS 7290 is being developed for both ADHD and adjunctive treatment of MDD, providing the company with opportunities to investigate OX2R activation across distinct neuropsychiatric indications.
While these conditions have different clinical characteristics, both involve complex neurological processes that can affect attention, cognition and daily functioning.
The company’s research strategy is focused on understanding whether modulation of orexin signaling could provide therapeutic benefits in these settings.
The Phase 2 MDD trial will be particularly important in establishing the initial safety and tolerability profile of ALKS 7290 in combination with standard antidepressant medications. The secondary efficacy assessments will also help determine whether the treatment produces improvements in depressive symptom severity compared with placebo.
The expected enrollment of approximately 180 participants should provide a clinical dataset to support the evaluation of the investigational therapy during the six-week treatment period.
Further development decisions will depend on the clinical findings and the overall assessment of safety, tolerability and potential efficacy.
Additional studies may be required to establish the treatment’s clinical profile, determine appropriate dosing and evaluate its longer-term effects if the initial results support continued development.
Study Registration and Company Outlook
Additional information about the Phase 2 clinical study is available through the ClinicalTrials.gov database under registration number NCT07901179.
The trial will evaluate ALKS 7290 in approximately 180 adults with major depressive disorder receiving standard antidepressant therapy. Participants will receive either the investigational OX2R agonist or placebo for six weeks, with safety and tolerability serving as the primary study objective.
For Alkermes, the initiation of this clinical program represents continued progress in its efforts to develop innovative treatments for neuropsychiatric conditions.
By investigating orexin 2 receptor activation, the company is exploring a biological pathway with potential relevance to wakefulness, attention, cognition and mood regulation. The Phase 2 study will provide an opportunity to assess whether this approach could complement existing antidepressant therapies and potentially address persistent symptoms in adults with MDD.
As the clinical program progresses, the findings will help clarify the therapeutic potential of ALKS 7290 and inform its future development strategy.
Through its expanding orexin receptor agonist portfolio, Alkermes aims to explore new treatment mechanisms across multiple neuropsychiatric indications and contribute to the development of additional therapeutic options for patients whose conditions remain challenging to manage with currently available treatments.
About ALKS 7290
ALKS 7290 is a novel, investigational, oral orexin 2 receptor (OX2R) agonist in development for the treatment of attention-deficit hyperactivity disorder (ADHD) and as an adjunctive therapy to antidepressants in major depressive disorder (MDD). Orexin, a neuropeptide produced in the lateral hypothalamus, plays a crucial role in regulating wakefulness, and engages multiple downstream pathways and neural circuits relevant to attention, cognition and mood. 1
By targeting the orexin system, ALKS 7290 has the potential to address symptoms relevant to a broad range of disorders characterized by impairments in these domains. ALKS 7290 has been evaluated in a phase 1 study in healthy volunteers and adults living with ADHD, and is currently being evaluated in phase 2 studies in adults with ADHD and adults with MDD.
About Alkermes plc
Alkermes plc (Nasdaq: ALKS), a mid-cap growth and value equity, is a global biopharmaceutical company that seeks to develop innovative medicines in the field of neuroscience. The company has a portfolio of proprietary commercial products for the treatment of alcohol dependence, opioid dependence, schizophrenia, bipolar I disorder and narcolepsy.
Alkermes has established a leadership position in orexin biology and is advancing a portfolio of investigational orexin 2 receptor agonists for narcolepsy, idiopathic hypersomnia and other psychiatric and neurological disorders, including attention-deficit hyperactivity disorder (ADHD), major depressive disorder (MDD) and fatigue associated with multiple sclerosis and Parkinson’s disease. Headquartered in Ireland, Alkermes also has a corporate office and research and development center in Massachusetts and a manufacturing facility in Ohio. For more information, please visit Alkermes’ website at www.alkermes.com .