Will a Robust Pipeline Address the Major Depressive Disorder Treatment Conundrum?

In the contemporary world, major depressive disorder (MDD) is one of the diseases responsible for the greatest healthcare burden. In the United States, more than 24 million people suffer from major depressive disorder each year, while in Europe, about 20 million are diagnosed with the major depressive disorder each year.

These numbers might not be a true reflection owning to continuous ignorance about mental health issues as well as a social stigma associated with mental health conditions.

A plethora of pharmacological drugs from different classes acting by more than half a dozen mechanisms are available for the major depressive disorder treatment. However, a significant unmet need for major depressive disorder treatment still remains.

The currently available major depressive disorder medications used to treat includes antidepressants that act directly on monoamine mechanisms, impelling serotonin, norepinephrine receptors, and neurotransmitters for serotonin, norepinephrine, and dopamine. 

The recent approval of Spravato in 2020 was a breakthrough in the major depressive disorder treatment after a few decades of no novel MDD treatment. However, it has not impacted the major depressive disorder market significantly owing to its exorbitant cost and significant abuse potential.

It is firmly regulated and administered only under direct HCP supervision in accredited clinics and post-administration observation.

Thus, the struggle for major depressive disorder patients is not over. The challenges like the development of treatment resistance, treatment-associated side-effects, delayed therapeutic action, and abuse potential continues to be a roadblock in the major depressive disorder treatment.

High unmet needs warrant novel major depressive disorder therapies to cater to the needs of the people affected with MDD.

What’s Next in the MDD Treatment Landscape?

The leading major depressive disorder companies such as Takeda Pharmaceuticals, Forest Laboratories, Otsuka Pharmaceuticals, Janssen Research & Development, Axsome Therapeutics, AbbVie, SAGE Therapeutics, Minerva Neurosciences, Luye Pharma, Relmada Therapeutics, BioLite Inc., VistaGen Therapeutics, Praxis Precision Medicines, Intra-Cellular Therapies, Neurocrine Biosciences, Arrivo Bioventures, Sirstei Pharmaceuticals, Alto Neuroscience, Chase Therapeutics, Neumora Therapeutics, Inc., BlackThorn Therapeutics, Inc., Otsuka Pharmaceutical Co., Ltd., Fabre-Kramer Pharmaceuticals, Novartis, and others are developing drugs for major depressive disorder treatment. 

With the continuous efforts of these pharma companies in research and development, novel therapies in the major depressive disorder pipeline such as AXS-05 (Axsome Therapeutics), Travivo (Fabre-Kramer Pharmaceuticals), SAGE-217 (SAGE Therapeutics), CAPLYTA  (Intra-Cellular Therapies), LY03005 (Luye Pharma), cariprazine (AbbVie), seltorexant (Minerva Neurosciences), REL-1017 (Relmada Therapeutics), and PH10 (VistaGen Therapeutics), are expected to enter the United States, EU5 (Germany, Italy, France, Spain, the United Kingdom) and Japan major depressive disorder market in next few years.

Among all the analysts, AXS-05 is currently the talk of the town. The asset is anticipated to achieve high major depressive disorder treatment market penetration owing to its rapid action and favorable safety and efficacy profile. It is expected to enter the United States anytime in 2022. Its early entry and promising efficacy could raise the bar for other assets in the development.

Other than Janssen’s Spravato, which is marketed for a limited patient population, none of the marketed products for treatment for depression has demonstrated rapid antidepressant effects. Thus, there is an excitement in the major depressive disorder treatment market if AXS-05 could manage to gain FDA approval and outperform Spravato and other assets in major depressive disorder clinical trials development.

Luye Pharma’s LY03005 is another key product that is currently in development in the central nervous system (CNS) therapeutic area. The drug is an extended-release tablet, a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine (SNDRI). As per the estimates, the drug is expected to enter the United States major depressive disorder treatment market by 2023.

Furthermore, compared with traditional antidepressant medications, SNDRI is expected to be relatively beneficial in helping preserve patients’ sexual function, as well as maintain a better safety profile, produce a more rapid onset, and provide better efficacy, addressing currently unmet medical needs.

An alternative drug with proclaimed rapid action is Sage-217. It is designed to provide a rapid-acting, sustainable major depressive disorder treatment option and could represent a breakthrough in the current management of depression. As per the data, it is anticipated to bridge the gap in the major depressive disorder treatment management for patients.

Unlike the currently marketed major depressive disorder therapies, zuranolone has a short course, with no sexual dysfunction or weight gain, and is rapid and sustained.

Caplyta by Intra-Cellular Therapies is an atypical antipsychotic that is the only major depressive disorder medication approved by the FDA to treat depressive disorders associated with bipolar I or bipolar II as a monotherapy or in combination with lithium or valproate.

The major depressive disorder medication is now being tested in a Phase III trial to treat MDD as adjunctive major depressive disorder treatment. The therapy offers convenient dosing, so if approved, CAPLYTA might ease the dosing schedule for patients with MDD.

Next comes REL-1017, a new chemical entity (NCE) and novel NMDA receptor (NMDAR) channel blocker that is currently in the Phase III stage of clinical development. The drug recently gained approval for treatment-resistant depression – both REL-1017 and the recently approved drug Spravato target the NMDA receptor.

However, unlike Spravato, REL-1017 has superior tolerability and lesser risk for drug diversion. The drug could enter the United States major depressive disorder treatment market by 2024 and directly compete with Spravato and other low-cost generics currently available.

Also, VistaGen Therapeutics’ PH10 is the potential new generation stand-alone antidepressant with a mechanism of action that is fundamentally different from all current antidepressants. PH10 has the potential for multiple applications in global depression markets. Unlike the currently marketed antidepressant, PH10 claims to be rapid.

However, it is expected to enter late in the US major depressive disorder treatment market compared to other competitors.

Lastly, PDC 1421, an extract of Polygala tenuifolia, is also part of the race. The company claims that ABV 1504 has the potential to obtain better therapeutic outcomes with fewer serious side effects compared to the current standard of care. It could come into the US major depressive disorder treatment market by 2026.

Why Should Pharma Players Be Optimistic About Major Depressive Disorder Market Growth?

Currently, the major depressive disorder market size accounts for more than USD 5,000 million. The market for major depressive disorder treatment is dominated by low-cost and generic therapies. What is alarming here is that the condition is still severely underdiagnosed.

An estimated two-thirds of all MDD cases in the United States go undiagnosed, owing to stigma or an inability to distinguish between clinical depressive symptoms. Furthermore, MDD patients are more likely to be nonadherent than non-depressed people.

Major depressive disorder treatment outcomes are poor due to non-persistence, premature medication discontinuation, and a continuous movement from one antidepressant prescription to another, which increases healthcare expenses.

In general, major depressive disorder is associated with a high economic burden, with the majority of the expense stemming from a person’s inability to be productive at work, which adds to the strain on the patient and caretaker.

However, new techniques, such as proteomics and metabolomics, could allow researchers to approach MDD in new directions and make new discoveries in upcoming years. Also, the increasing prevalence of the disease along with upcoming novel therapies would fuel the major depressive disorder market in the future.

Last but not least, there is an increasing effort by various organizations and governments to create awareness about MDD, thus, breaking the stigma and misconception about the disease.

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