MedPath

Trospium

Generic Name
Trospium
Brand Names
Trosec
Drug Type
Small Molecule
Chemical Formula
C25H30NO3
CAS Number
47608-32-2
Unique Ingredient Identifier
T4Y8ORK057
Background

Trospium is an antispasmodic agent used to treat the symptoms of overactive bladder, a condition that causes the bladder muscles to contract uncontrollably. An overactive bladder leads to an increased urge to urinate, frequent urination, and sometimes, loss of control over urination. Trospium is manufactured by Indevus Pharmaceutical Inc. and was granted FDA approval in 2007.

Indication

For the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency, detrusor instability and frequency of micturition.

Associated Conditions
Overactive Bladder Syndrome (OABS)

Xanomeline Trospium Shows Promising Cognitive Benefits in Schizophrenia Patients with Baseline Impairment

• Phase III trial results demonstrate that xanomeline trospium (XT), a novel muscarinic receptor-targeting drug, significantly improved cognitive function in schizophrenia patients with baseline cognitive impairment. • The study revealed 39% of cognitively impaired patients receiving XT achieved substantial improvement in executive function, sustained attention, and verbal recall, compared to 19% in the placebo group. • As the first FDA-approved antipsychotic targeting the acetylcholine system, XT shows unique advantages in addressing multiple symptom domains of schizophrenia, including positive, negative, and cognitive symptoms.

Sumitomo's Novel Schizophrenia Drug Ulotaront Fails to Meet Primary Endpoint in Phase 3 Trials

• Sumitomo Pharma America's ulotaront (SEP-363856), a novel TAAR1 and 5-HT1A agonist, failed to demonstrate statistical significance versus placebo in two Phase 3 trials for acute schizophrenia. • Despite showing favorable safety profile with fewer metabolic side effects compared to current antipsychotics, the drug's efficacy was masked by an unexpectedly high placebo response in the DIAMOND 1 and 2 studies. • The setback occurs amid ongoing development of other promising schizophrenia treatments, including Karuna's KarXT and Minerva's roluperidone, which are advancing toward potential market approval.

Zai Lab's KarXT Receives NMPA Acceptance for Schizophrenia Treatment in China

• China's NMPA has accepted Zai Lab's NDA for KarXT for treating schizophrenia in adults, addressing a significant unmet need. • Phase 3 trials in China showed KarXT significantly reduced schizophrenia symptoms compared to placebo, with a tolerable safety profile. • KarXT represents a novel class of treatment targeting muscarinic acetylcholine receptors, offering a new approach compared to traditional antipsychotics. • The NDA is supported by Phase 1 and Phase 3 China studies, along with data from global EMERGENT clinical programs, indicating robust evidence.

Cobenfy Shows Cognitive Benefits in Schizophrenia Patients with CANTAB Assessment

• Cobenfy, a novel schizophrenia treatment targeting M1/M4 muscarinic receptors, has received FDA approval and demonstrates efficacy in reducing both positive and negative symptoms. • A post-hoc analysis of Phase 3 trials using Cambridge Cognition's CANTAB reveals cognitive performance improvements in schizophrenia patients with pre-existing cognitive impairment. • The CANTAB assessment tool proves instrumental in tracking cognitive benefits, enhancing data collection, and accelerating the development of effective schizophrenia treatments. • Cobenfy represents a breakthrough as the first monotherapy to demonstrate replicable cognitive benefits, independent of its impact on positive and negative symptoms.

Xanomeline/Trospium Chloride (COBENFY™) Approved for Schizophrenia Treatment

• Xanomeline/trospium chloride (COBENFY™) has received its first approval in the USA for treating schizophrenia in adults, marking a new approach in psychiatric medication. • The oral, fixed-dose combination targets muscarinic acetylcholine receptors, with xanomeline acting as an agonist at M1 and M4 receptors in the brain. • Trospium chloride is included to mitigate peripheral cholinergic adverse effects associated with xanomeline, enhancing tolerability. • This approval signifies a milestone in the development of novel treatments for schizophrenia, addressing efficacy and side effect profiles.

Reviva Pharmaceuticals Reports Promising Preliminary OLE Data for Brilaroxazine

Reviva Pharmaceuticals has announced encouraging preliminary data from its Open-Label Extension (OLE) study for brilaroxazine, showing favorable safety, tolerability, and adherence rates. The company is gearing up for its confirmatory Phase III RECOVER-2 trial, with plans to launch in early 2025. Additionally, Reviva has successfully raised $18 million to fund the upcoming trial and support operations until approval.

Landmark Medical Advances of 2024: HIV Prevention, Schizophrenia Treatment, and More

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Alzheimer's Disease Pipeline Shows Promise with 120+ Therapies in Development

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AbbVie's Emraclidine Fails, Bolstering BMS's Lead in Schizophrenia Treatment

• AbbVie's emraclidine failed to demonstrate statistically significant improvement in schizophrenia symptoms in Phase II trials, a setback for the muscarinic pathway approach. • Bristol Myers Squibb's Cobenfy (KarXT), a muscarinic agonist, now stands as the frontrunner in schizophrenia treatment after AbbVie's trial failures. • Neurocrine Biosciences is advancing NBI-1117568, an oral muscarinic M4 selective agonist, with Phase III trials planned for early 2025, showing a potential path forward. • Other companies like Neumora Therapeutics and Reviva Pharmaceuticals are also exploring novel mechanisms for schizophrenia treatment, indicating a dynamic therapeutic landscape.

AbbVie's Emraclidine Fails in Schizophrenia Trials, Analysts Still Bullish on Immunology Portfolio

• AbbVie's emraclidine failed to meet the primary endpoint in two Phase 2 trials for schizophrenia, showing no statistically significant improvement in PANSS scores compared to placebo. • Analysts suggest Bristol Myers Squibb's Cobenfy (xanomeline and trospium chloride) is now positioned to face less competition in the schizophrenia market following AbbVie's setback. • Despite the disappointing results, analysts maintain a positive outlook on AbbVie, emphasizing the strength and growth potential of its immunology franchise. • The failure raises questions about AbbVie's neuroscience strategy, though the company's acquisition of Cerevel still holds promise with Tavapadon showing positive Phase 3 results in Parkinson's disease.

AbbVie's Emraclidine Fails in Phase II Schizophrenia Trials, Stock Plummets

• AbbVie's emraclidine, a novel M4-selective positive allosteric modulator, failed to meet the primary endpoint in two Phase II trials for schizophrenia, EMPOWER-1 and EMPOWER-2. • The trials assessed multiple doses of emraclidine as a once-daily, oral monotherapy but did not show a significant reduction in PANSS total score compared to placebo. • Following the announcement, AbbVie's stock price fell over 12%, while Bristol Myers Squibb's stock rose, potentially due to their competing drug KarXT showing positive results. • AbbVie will continue to analyze the data to determine the next steps, reaffirming its commitment to developing therapies for psychiatric and neurological disorders.

AbbVie's Emraclidine Fails in Phase II Schizophrenia Trials, Stock Plummets

• AbbVie's emraclidine, a novel M4-selective positive allosteric modulator, failed to meet the primary endpoint in two Phase II trials for schizophrenia. • The EMPOWER-1 and EMPOWER-2 trials did not show a significant reduction in PANSS total score compared to placebo, leading to AbbVie stock dropping over 12%. • Bristol Myers Squibb's stock rose by over 11% following AbbVie's announcement, as their KarXT schizophrenia treatment shows promising Phase III results. • KarXT, acquired by BMS through the Karuna Therapeutics acquisition, is projected to reach $2.81 billion in US sales by 2033, contrasting with emraclidine's setback.

Zai Lab Reports Strong Q3 2024 Growth, Highlights Pipeline Advances Including KarXT and ZL-1310

• Zai Lab's Q3 2024 net product revenue reached $101.8 million, a 47% year-over-year increase, driven by VYVGART, ZEJULA, and NUZYRA sales. • A China bridging study of KarXT in schizophrenia showed positive results, with regulatory submission expected in early 2025, potentially expanding treatment options. • Phase 1 data for ZL-1310, a DLL3-targeted ADC for extensive-stage SCLC, demonstrated promising antitumor activity, suggesting best-in-class potential. • The company anticipates launching three products in mainland China by the end of 2024 and aims for up to four regulatory submissions to the NMPA in the next six months.

AbbVie's Emraclidine Fails to Meet Primary Endpoint in Phase 2 Schizophrenia Trials

• AbbVie's emraclidine, an oral monotherapy for schizophrenia, did not achieve statistically significant improvement in two Phase 2 trials, causing AbbVie shares to decline. • Despite the setback, AbbVie will continue analyzing the data to determine the next steps for emraclidine's development in psychiatric disorders. • AbbVie's focus remains on its pipeline of innovative therapies, particularly after acquiring Cerevel Therapeutics for $8.7 billion to expand its offerings in schizophrenia treatment. • Bristol-Myers Squibb's schizophrenia drug, Cobenfy (KarXT), recently gained FDA approval, following their acquisition of Karuna Therapeutics for $14 billion.

KarXT (Cobenfy) Approved for Schizophrenia: A Novel, Nondopaminergic Approach

• The FDA approved KarXT (Cobenfy) on September 26, 2024, marking the first new mechanism of action for schizophrenia treatment since 1954. • KarXT combines xanomeline and trospium to modulate brain circuits via muscarinic cholinergic receptors, offering a nondopaminergic approach to managing schizophrenia symptoms. • Clinical trials (EMERGENT-1, -2, -3, -4, -5) demonstrated significant improvements in PANSS scores and supported the long-term safety and efficacy of KarXT. • Cobenfy's unique mechanism and adverse event profile necessitate prescriber education to optimize its use as a novel treatment option for schizophrenia.

Teva's TEV-749 Shows Promise in Phase III Trial for Schizophrenia

• Teva's TEV-749 (olanzapine) demonstrated statistically significant improvements in schizophrenia symptoms in the Phase III SOLARIS trial over eight weeks. • The trial assessed three doses of TEV-749, showing improvements in social functioning and quality of life compared to placebo. • TEV-749, administered via subcutaneous injection, aims to improve patient adherence and reduce the risk of post-injection delirium/sedation syndrome (PDSS). • If approved, TEV-749 is projected to reach annual sales of $315 million by 2030 in the US, offering a new long-acting treatment option.

Zai Lab's KarXT Shows Positive Phase 3 Results for Schizophrenia Treatment in China

• Zai Lab's Phase 3 trial of KarXT in China met its primary endpoint, demonstrating a statistically significant 9.2-point reduction in PANSS total score compared to placebo at Week 5. • The trial also met all key secondary endpoints, showing significant improvements in positive and negative symptoms of schizophrenia, as measured by PANSS subscales and CGI-S. • KarXT exhibited a tolerable safety profile in the trial, with no new or unexpected safety signals observed compared to previous global studies. • Zai Lab plans to submit a New Drug Application (NDA) to China's National Medical Products Administration (NMPA) for KarXT in early 2025 based on these results.

Zai Lab's KarXT Shows Positive Phase 3 Results in China for Schizophrenia

• Zai Lab's Phase 3 trial of KarXT in China met its primary endpoint, demonstrating a statistically significant reduction in PANSS total score compared to placebo. • The trial also met all key secondary endpoints, showing significant improvements in positive and negative symptoms of schizophrenia. • KarXT exhibited a tolerable safety profile in the trial, with no new or unexpected safety signals observed. • Zai Lab plans to submit a New Drug Application (NDA) to China's NMPA for KarXT in early 2025 based on these results.

Zai Lab's KarXT Shows Positive Phase 3 Results for Schizophrenia Treatment in China

• Zai Lab's Phase 3 trial of KarXT in China met its primary endpoint, demonstrating a statistically significant 9.2-point reduction in PANSS total score compared to placebo at Week 5. • The trial also met all key secondary endpoints, showing significant improvements in PANSS positive and negative symptom subscales, and the CGI-S scale. • KarXT's safety profile in the trial was consistent with previous global studies, with no new or unexpected safety signals observed. • Zai Lab plans to submit a New Drug Application (NDA) to China’s NMPA in early 2025 based on these positive results.

FDA Approves Perioperative Nivolumab for Resectable NSCLC Without EGFR or ALK Mutations

• The FDA approved nivolumab with platinum-doublet chemotherapy as neoadjuvant treatment, followed by nivolumab as adjuvant treatment for resectable NSCLC. • The approval is specifically for patients without EGFR mutations or ALK rearrangements, based on the CheckMate-77T trial results. • The Opdivo regimen showed a 42% reduction in the risk of disease recurrence, progression, or death compared to chemotherapy and placebo. • This approval expands Opdivo's role in NSCLC, now covering both neoadjuvant-only and perioperative treatment regimens.
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