Definition
Bipolar disorder is a multifactorial condition characterized by fluctuating mood states BD is a multifactorial psychiatric mood disorder influenced by social, environmental, and genetic risk factors underlying its etiology. The disorder is characterized by fluctuating mood states, such as mania and depression, interspersed with periods of wellbeing over days and weeks. BD describes a range of disease subtypes, including BD type I, BD type II, and cyclothymia.
Latest key takeaways
- Datamonitor Healthcare estimates that in 2021, there were 47.7 million prevalent cases of bipolar disorder (BD) worldwide, and forecasts that number to increase to 50.4 million prevalent cases by 2027.
- The BD market is highly genericized, consisting of antipsychotics, anticonvulsants, and mood stabilizers such as lithium. The atypical antipsychotic market is the most dominant of the drug classes indicated for BD, and the oral atypical antipsychotic market is highly competitive with many generic alternatives available. The atypical long-acting injectable (LAI) antipsychotic market currently sees little competition and is therefore one of the key areas to target for growth, along with the development of drugs focusing on other underserved BD patient segments.
- One of the most impactful recent events to have occurred in the BD space is the FDA approval (in April 2022) of BioXcel’s Igalmi for the acute treatment of agitation associated with type I or II BD. In the Phase III trial, treatment with Igalmi led to rapid and durable improvements in acute agitation, superior to placebo. Its sublingual film formulation means it is easy to administer, avoiding the invasive administration of antipsychotics or benzodiazepines currently used for severe agitation in acute psychiatric facilities.
- As physicians and patients become more accustomed to the dosing regimens of LAIs and their associated benefits, their uptake will increase. Pharmaceutical treatment compliance is a major issue in BD, and physicians will encourage switching to LAI formulations to reduce relapses. There are only two key brands in the BD LAI atypical antipsychotic market: Risperdal Consta, the first of its kind approved for BD, requiring dosing every two weeks; and Abilify Maintena, which only requires once-monthly administration.
- Seroquel/Seroquel XR has a robust clinical profile in BD due to its strong efficacy as both a monotherapy and adjuvant in the treatment of BD mania, as a BD maintenance treatment, and in BD depression. The drug is one of few therapies specifically approved for BD depression. As a monotherapy in trials, treatment in both type I and II BD patients elicited some of the greatest improvements over placebo that have been witnessed in controlled BD studies. As an atypical antipsychotic, Seroquel/Seroquel XR has modest safety/tolerability profiles at best. Nevertheless, both formulations are genericized, and the market share of this brand in BD has been cannibalized and will continue to plummet.
- Abilify Maintena is one of the few approved LAI antipsychotics available for BD, and its increasing uptake means it is likely to dominate the bipolar LAI market. The drug boasts one of the highest rates of relapse reduction over placebo in clinical trials, granting it a position towards the top of the BD maintenance treatment algorithm. Abilify Maintena can be administered once monthly, surpassing Risperdal Consta’s dosing regimen of once every two weeks, and this less frequent dosing provides further aid to the mitigation of compliance issues so often seen with antipsychotics. Additionally, a new formulation of aripiprazole which can be administered once every two months is nearing approval. With the associated benefits of LAIs, and as both physicians and patients become more accustomed to the dosing regimens, the LAI market should see sizable growth.
- Intra-Cellular Therapies has gathered encouraging data from trials investigating the adjunctive and monotherapy use of Caplyta, which was approved by the FDA for type I and II BD depression in December 2021. Latuda is the only other therapy approved as an adjunctive/monotherapy treatment for BD depression, but has only demonstrated efficacy in type I BD depressed patients. Intra-Cellular is therefore offering a much-needed option in this subpopulation, and, moreover, Caplyta displayed minimal motor adverse events in pivotal trials, compared to the higher rates witnessed in Latuda’s regulatory studies.
- Lybalvi, a distinct formulation of olanzapine and the novel opioid receptor antagonist samidorphan, is an antipsychotic drug designed to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain, a firmly established side effect of most antipsychotics. The drug has demonstrated similar efficacy to olanzapine in schizophrenia patients and a statistically significant reduction in weight gain. In addition to its schizophrenia indication, it is now available to adults with type I BD.
- Pipeline drug developers are targeting unmet needs in BD for which there are currently limited options available, and consequently these pipeline drugs will act to drive growth in the market, if successfully approved. Cyclurad is a proprietary formulation of D-cycloserine and lurasidone under development by NeuroRx for the treatment of bipolar depression in patients with acute suicidality. If successful, this would be the first drug approved to treat this specific patient population. Additionally, Celon Pharma is developing an inhaled esketamine formulation, Falkieri, which has the potential to be the first therapy approved for treatment-resistant bipolar depression.
- High-impact upcoming events for drugs in the BD space comprise topline Phase III results for Cyclurad and Caplyta, and a US approval decision for two-monthly aripiprazole.
CONTENTS
6 OVERVIEW
6 Latest key takeaways
8 DISEASE BACKGROUND
8 Definition
10 Patient segmentation
11 TREATMENT
11 Drug therapy is used in the vast majority of bipolar disorder patients
11 Therapy can be integrated with non-pharmacological interventions to improve patient outcomes
12 The goal of treatment is to bring patients to a state of recovery and minimize relapses
12 Bipolar disorder treatment guideline recommendations by drug class
13 Acute mania
14 Acute depression
15 Maintenance therapy
17 EPIDEMIOLOGY
17 Prevalence methodology
20 MARKETED DRUGS
27 PIPELINE DRUGS
32 KEY REGULATORY EVENTS
32 BioXcel Gets First Approval With Igalmi For Neuropsychiatric Agitation
33 PROBABILITY OF SUCCESS
34 CLINICAL TRIAL LANDSCAPE
35 Sponsors by status
36 Sponsors by phase
38 DRUG ASSESSMENT MODEL
38 Marketed drugs
40 Pipeline drugs
42 MARKET DYNAMICS
43 FUTURE TRENDS
43 The LAI atypical antipsychotic market will see increasing growth and little competition
43 The oral atypical antipsychotic market will see further widespread genericization
44 New market entrants will be directed towards underserved patient segments and improved tolerability
45 CONSENSUS FORECASTS
49 KEY UPCOMING EVENTS
50 KEY OPINION LEADER INSIGHTS
51 UNMET NEEDS
51 BD depression
51 Delay of correct diagnosis
51 Cognitive impairment
52 BIBLIOGRAPHY
53 APPENDIX
LIST OF FIGURES
9 Figure 1: DSM-5 diagnostic criteria for mood episodes based on symptoms
10 Figure 2: DSM-5 diagnostic criteria for bipolar disorder subtypes
11 Figure 3: Psychological interventions for bipolar disorder
12 Figure 4: Guidelines for bipolar disorder treatment
13 Figure 5: Drug classes recommended in bipolar disorder treatment guidelines, by disease phase and line of therapy
14 Figure 6: Guideline recommendations for acute mania, by line of treatment
15 Figure 7: Guideline recommendations for acute depression, by line of treatment
16 Figure 8: Guideline recommendations for maintenance therapy, by line of treatment
19 Figure 9: Trends in prevalent cases of bipolar disorder, 2018–27
27 Figure 10: Overview of pipeline drugs for bipolar disorder in the US
27 Figure 11: Pipeline drugs for bipolar disorder, by company
28 Figure 12: Pipeline drugs for bipolar disorder, by drug type
28 Figure 13: Pipeline drugs for bipolar disorder, by classification
33 Figure 14: Probability of success in the bipolar disorder pipeline
34 Figure 15: Clinical trials in bipolar disorder
34 Figure 16: Top 10 drugs for clinical trials in bipolar disorder
35 Figure 17: Top 10 companies for clinical trials in bipolar disorder
35 Figure 18: Trial locations in bipolar disorder
36 Figure 19: Bipolar disorder trials status
37 Figure 20: Bipolar disorder trials sponsors, by phase
38 Figure 21: Datamonitor Healthcare’s drug assessment summary for bipolar disorder
42 Figure 22: Market dynamics in bipolar disorder
43 Figure 23: Future trends in bipolar disorder
49 Figure 24: Key upcoming events in bipolar disorder
LIST OF TABLES
18 Table 1: Prevalent cases of bipolar disorder, 2018–27
21 Table 2: Marketed drugs for bipolar disorder
29 Table 3: Pipeline drugs for bipolar disorder in the US
46 Table 4: Historical global sales, by drug ($m), 2017–21
47 Table 5: Forecasted global sales, by drug ($m), 2022–26