Breakthrough Clinical Results
Neurocrine Biosciences has initiated a Phase 3 registrational program for NBI-1117568, an oral muscarinic M4 selective receptor agonist, as a potential treatment for schizophrenia. This follows positive Phase 2 data showing a statistically significant reduction in PANSS scores. NBI-1117568, discovered by Nxera Pharma, is the first NxWave™-designed molecule to enter Phase 3. The Phase 3 study is a global, double-blind, placebo-controlled trial expected to enroll approximately 280 patients. Neurocrine will pay Nxera a $15 million milestone payment upon dosing of the first patient in the Phase 3 study.
Key Highlights
- Phase 3 trial of NBI-1117568 for schizophrenia initiated by Neurocrine Biosciences.
- Positive Phase 2 data supported the initiation of the Phase 3 program.
- NBI-1117568 is an oral, muscarinic M4 selective receptor agonist.
- The trial will enroll approximately 280 adults with schizophrenia.
Incidence and Prevalence
Schizophrenia's Global Burden: Latest Estimates
The most recent data from PubMed regarding the global incidence and prevalence of schizophrenia comes from a 2023 study analyzing data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) up to 2019. This study reveals:
- Raw Prevalence Increase: From 1990 to 2019, the raw prevalence of schizophrenia increased significantly, from 14.2 million to 23.6 million cases globally. This represents an increase of over 65%.
- Stable Age-Standardized Prevalence: While the raw number of cases increased, the age-standardized prevalence remained stable globally. This suggests that the increase in raw prevalence is largely due to population growth and aging, rather than a true increase in the proportion of the population affected by schizophrenia.
- Incidence Increase: The raw incidence of schizophrenia also increased from 941,000 to 1.3 million new cases annually between 1990 and 2019, a rise of over 37%. Similar to prevalence, age-standardized incidence remained stable globally.
- Disability-Adjusted Life Years (DALYs) Increase: DALYs, a measure of overall disease burden, increased by over 65% during the same period, rising from 9.1 million to 15.1 million. Again, age-standardized DALYs remained stable globally.
Other Key Findings and Considerations:
- Socio-Demographic Index (SDI) Differences: In high-SDI countries, both prevalence and DALYs increased, while in low-SDI countries, age-standardized incidence decreased, and DALYs remained stable. This highlights the potential for underdiagnosis and undertreatment in low-SDI settings.
- Sex Differences: The male-to-female ratio of schizophrenia burden remained stable overall (1.1:1) over the 30-year period. However, this ratio shifts with age, with females exhibiting higher raw prevalence after age 65. This is likely due to differences in age of onset (earlier in males) and life expectancy (longer in females).
- Underestimation of Burden: The GBD study does not account for mortality directly attributable to schizophrenia, which likely leads to an underestimation of the true burden of the disease.
Earlier Estimates:
Other GBD studies from earlier years provide slightly different estimates, reflecting the ongoing nature of data collection and analysis in this field. For example:
- GBD 2017: Estimated 1.13 million incident cases and 12.66 million DALYs globally in 2017. The global age-standardized incidence rate (ASIR) decreased slightly from 1990 to 2017, while the age-standardized DALY rate (ASDR) remained stable.
- GBD 2016: Estimated a global age-standardized point prevalence of 0.28% in 2016, with no significant sex differences observed. Globally, prevalent cases rose from 13.1 million in 1990 to 20.9 million in 2016.
It's important to note that estimates of schizophrenia prevalence and incidence can vary depending on the methodology used, the populations studied, and the diagnostic criteria applied. The GBD studies provide valuable insights into the global burden of schizophrenia, but continued research and improved data collection are essential for refining these estimates and understanding the complex epidemiology of this disorder.
Economic Burden
Schizophrenia's Economic Burden: USA and Europe
The economic burden of schizophrenia is substantial in both the USA and Europe, although direct comparisons are hampered by variations in methodology, healthcare systems, and data availability. Here's a summary of the latest available information:
USA:
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A 2023 study estimated the excess economic burden of schizophrenia in the US in 2019 at $343.2 billion. This represents a near doubling of the burden since 2013 ($155.7 billion). This massive figure includes:
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$251.9 billion (73.4%) in indirect costs, primarily driven by caregiving ($112.3 billion), premature mortality ($77.9 billion), and unemployment ($54.2 billion).
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$62.3 billion (18.2%) in direct healthcare costs.
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$35.0 billion (10.2%) in direct non-healthcare costs, offset by $6.0 billion (1.7%) in avoided basic living costs.
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An earlier study (2014) estimated the annual cost of schizophrenia in the US to be $62.7 billion in 2002. This included $22.7 billion in direct healthcare costs, $7.6 billion in direct non-healthcare costs, and $32.4 billion in indirect costs, with unemployment being the largest contributor.
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Another study focusing on treatment-resistant schizophrenia (TRS) estimated that TRS adds more than $34 billion in annual direct medical costs in the USA. This study also highlighted the significant loss in quality of life associated with TRS.
Europe:
European data is more fragmented and often older. Cost estimates are generally lower than in the US, but still substantial.
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A 2016 review of cost-of-illness studies found the annual societal cost per patient varied widely, from $5,818 in Thailand (not European, but included in the review for comparison) to $94,587 in Norway (2015 USD). The lifetime societal cost per patient was estimated to be $988,264 in Australia.
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A 2014 review found annual costs for schizophrenia ranging from $94 million to $102 billion per country. Indirect costs constituted 50-85% of the total costs.
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A 2021 study focusing on Huntington's Disease (which has some overlapping features with schizophrenia in terms of burden) found average annual direct medical costs of €12,663, non-direct medical costs of €2,984, and indirect costs of €47,576 in five European countries and the USA. Costs were higher in later stages of the disease.
Challenges and Gaps:
- Data Scarcity and Heterogeneity: European data is often older and less comprehensive than US data. Methodological differences make comparisons difficult.
- Indirect Cost Measurement: Indirect costs, including lost productivity and caregiver burden, are often underestimated or not fully captured.
- Treatment-Resistant Schizophrenia: The high cost of TRS highlights the need for more effective treatments.
- Impact of New Treatments: The impact of newer antipsychotic medications and other interventions on costs and outcomes needs further investigation.
Conclusion:
Schizophrenia imposes a massive economic burden on both the USA and Europe. More research, particularly in Europe, is needed to fully quantify the burden and to evaluate the cost-effectiveness of interventions. Standardized methodologies and comprehensive data collection are crucial for accurate comparisons and informed policy decisions.
NBI-1117568 (Suzetrigine) is primarily being investigated for its efficacy in treating acute pain. Two Phase 3 clinical trials have been conducted, focusing on post-surgical pain management after abdominoplasty and bunionectomy. These trials compared suzetrigine to a placebo and an active control (hydrocodone bitartrate/acetaminophen or HB/APAP). The results showed statistically significant pain reduction with suzetrigine compared to placebo, but not superiority to HB/APAP. The provided texts do not mention any other indications for which NBI-1117568 is currently being trialed. The intervention models for the acute pain trials involved a randomized, double-blind, placebo- and active-controlled design. Participants received either suzetrigine (100mg then 50mg every 12 hours), HB/APAP (5/325mg every 6 hours), or a placebo for 48 hours after surgery. The primary endpoint was the time-weighted sum of pain intensity difference from 0-48 hours (SPID48) versus placebo. Key secondary endpoints included SPID48 versus HB/APAP and time to a 2-point reduction in pain from baseline versus placebo.
