The bipolar disorder pipeline is moderate in size containing agents in a range of different drug classes, including both tried and tested, and novel classes. However, it is unlikely that any product in the late-stage pipeline will be able to displace lithium as the gold standard of treatment, says GlobalData, a leading data and analytics company.

Philippa Salter, Neurology Analyst at GlobalData, comments: “The atypical antipsychotics have a strong presence in the bipolar disorder pipeline. This is despite the presence of 13 atypical antipsychotic products, as well as generics, already on the market for managing acute manic symptoms. Pipeline agents will therefore need to demonstrate significant advantages over currently available products to best compete in the market, a point emphasized by key opinion leaders (KOLs) interviewed by Globaldata.”

One way in which these agents can differentiate themselves is through their safety profiles.Marketed atypical antipsychotics are associated with effects on metabolic parameters (such as weight gain, hyperglycemia, and dyslipidemia) and extrapyramidal symptoms (dystonia, akathisia, parkinsonism, and tardive

dyskinesia). KOLs agreed that despite the competition, space remains in the bipolar disorder market for atypical antipsychotics with significantly improved safety profiles.

Salter continues: “Even with improvements in safety, the lack of novelty in this approach means that new atypical antipsychotics are likely to result only in incremental advances in treatment efficacy, especially for products that are reformulations of existing drugs, such as risperidone extended release (ER) and aripiprazole controlled release (CR), both in Phase I development.”

Beyond the atypical antipsychotics, there are a variety of novel mechanisms of action (MoAs) in the bipolar disorder pipeline that developers are hoping will offer improved efficacy and safety compared to the available products. Not only can new MoAs provide a point of difference for developers looking to enter this competitive market, but they may also be used to target new patient sub-populations in which competition is lower.

Salter adds: “For example, if they reach the market, Falkieri would become the first approved treatment for treatment-resistant bipolar depression, and Cyclurad would become the first approved treatment for acute suicidal ideation/behavior associated with bipolar depression. There is a high unmet need for effective treatments for bipolar depression, and suicide rates are higher in bipolar disorder patients than in the general population, so these are important patient populations to be targeting.”

GlobalData anticipates that six products in the late-stage pipeline will enter the bipolar disorder market prior to 2030. These products are: BioXcel Therapeutics’ dexmedetomidine, Vanda Pharmaceuticals’ Fanapt (iloperidone), Jina Pharmaceuticals’ endoxifen, NRX Pharmaceuticals’ Cyclurad (cycloserine + lurasidone), Sunovion Pharmaceuticals’ SEP-4199 (amisulpride), and Celon Pharma’s Falkieri (esketamine). Additionally, Intra-Cellular Therapies’ Caplyta (lumateperone) received FDA approval for the treatment of depressive episodes associated with bipolar I or II disorder in December 2021 and is anticipated to launch later this year.

Salter concludes: “Although there are several promising agents in the pipeline, it is unlikely that lithium will be replaced as the gold standard for bipolar disorder, given its efficacy in treating both bipolar mania and bipolar depression, as well as being effective for both acute and maintenance therapy. It is also unlikely that these agents will alter the treatment paradigm; more likely they will become supplementary options that can be added to existing treatments or used when more established therapies fail.”