CLINICAL TRIALS PROFILE FOR XERMELO

All Clinical Trials for XERMELO

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03790111 ↗	A Safety and Efficacy Study of XERMELO® + First-line Chemotherapy in Patients With Advanced Biliary Tract Cancer	Active, not recruiting	Lexicon Pharmaceuticals	Phase 2	2019-03-13	A Phase 2, multicenter, open-label, 2-stage study to assess the safety, tolerability, and efficacy of XERMELO in combination with first-line (1L) therapy (cisplatin [cis] plus gemcitabine [gem])
NCT03790111 ↗	A Safety and Efficacy Study of XERMELO® + First-line Chemotherapy in Patients With Advanced Biliary Tract Cancer	Active, not recruiting	TerSera Therapeutics LLC	Phase 2	2019-03-13	A Phase 2, multicenter, open-label, 2-stage study to assess the safety, tolerability, and efficacy of XERMELO in combination with first-line (1L) therapy (cisplatin [cis] plus gemcitabine [gem])
NCT03910387 ↗	Telotristat Ethyl to Promote Weight Stability in Patients With Advanced Stage Pancreatic Cancer	Recruiting	Lexicon Pharmaceuticals	Phase 2	2019-04-17	This phase II trial studies how well telotristat ethyl works in promoting weight stability in patients with pancreatic adenocarcinoma that has come back and spread to other places in the body. Telotristat ethyl may decrease bowel movements which may make patients gain weight. Stabilizing weight may help patients tolerate chemotherapy better and improve longevity.
NCT03910387 ↗	Telotristat Ethyl to Promote Weight Stability in Patients With Advanced Stage Pancreatic Cancer	Recruiting	TerSera Therapeutics LLC	Phase 2	2019-04-17	This phase II trial studies how well telotristat ethyl works in promoting weight stability in patients with pancreatic adenocarcinoma that has come back and spread to other places in the body. Telotristat ethyl may decrease bowel movements which may make patients gain weight. Stabilizing weight may help patients tolerate chemotherapy better and improve longevity.
NCT03910387 ↗	Telotristat Ethyl to Promote Weight Stability in Patients With Advanced Stage Pancreatic Cancer	Recruiting	Emory University	Phase 2	2019-04-17	This phase II trial studies how well telotristat ethyl works in promoting weight stability in patients with pancreatic adenocarcinoma that has come back and spread to other places in the body. Telotristat ethyl may decrease bowel movements which may make patients gain weight. Stabilizing weight may help patients tolerate chemotherapy better and improve longevity.
NCT04065165 ↗	Lanreotide Combined With Telotristat Ethyl or Placebo for the First-line Treatment in Patients With Advanced Well Differentiated Small Intestinal Neuroendocrine Tumours (siNET) With Highly-functioning Carcinoid Syndrome	Withdrawn	Ipsen	Phase 3	2020-04-01	This is a randomized phase III clinical trial of Lanreotide combined with Telotristat ethyl or placebo for the first-line treatment in patients with advanced well differentiated small intestinal neuroendocrine tumours (siNET) with highly-functioning carcinoid syndrome to test whether telotristat ethyl plus lanreotide is more effective than placebo plus lanreotide in reducing the number of daily bowel movements. In addition, the study allows evaluation of the biochemical response (5-HIAA and chromogranin-A), the reduction in the number of daily cutaneous flushing episodes, the improvement in abdominal pain/discomfort, health-related quality of life, improvement in gastro-intestinal and endocrine symptoms, changes in emotional functioning, the impact of discontinuation of telotristat ethyl/placebo on HRQOL and symptoms, and the safety and toxicity of the treatment. Patients will enter into a screening/run-in period of 1 week to establish baseline characteristics and symptomatology. The baseline assessment of daily bowel movement, as assessed in an electronic diary, will be averaged over the run-in period. Following the screening/run-in period, patients will be randomly assigned (1:1) to either the control arm or the experimental arm for 12 months. Randomization will be stratified according to the grade of tumour differentiation (grade 1 vs. grade 2) and by baseline number of bowel movements per day (4-6 versus >6). A total of 94 patients will be randomly assigned (1:1) to either arm. Upon randomization, all patients will enter the 12-month treatment period with lanreotide + telotristat ethyl/placebo (blinded). In the experimental arm, patients will receive the deep subcutaneous injection of lanreotide (120 mg) every 28 days and 250 mg orally three times daily (TID) of telotristat ethyl for 12 months. In the control arm, patients will receive the deep subcutaneous injection of lanreotide every 28 days (120 mg) and placebo orally TID for 12 months. After completion of a minimum of 6 months on randomized blinded-treatment, the protocol allows for patients on treatment with telotristat ethyl/placebo to be unblinded in the event of "lack of symptom control". Unblinding due to "lack of symptom control" can happen at any time between 6 and 12 months of the blinded-treatment period. After unblinding, patient will interrupt protocol treatment and will be further treated as per clinician discretion. All patients will be unblinded after a maximum of 12 months on randomized blinded-treatment. After a follow-up of 12 months, patients will go off study except patients with carcinoid heart disease. Patients off study will be further treated as per clinician discretion. Patients with carcinoid heart disease will continue open-label treatment on study (lanreotide + telotristat ethyl or lanreotide alone according to what they were receiving at unblinding at 12 months) for 4 additional years (open-label extension period). Patients with carcinoid heart disease who discontinue protocol treatment before 12 months will also enter the extension period for additional follow-up. Additional follow-up will last 4 years for these patients and will include 6-monthly cardiological assessments. All efficacy analyses will be conducted in the Intention-to-treat population as primary analyses i.e. all 94 randomized patients will be analyzed in the arm they were allocated by randomization. Safety analyses will be performed on the Safety population i.e. on all patients who have received at least one dose of the study drugs. The translational research projects include blood metabolite discovery and targeted assays to find new biomarker candidates of response to Telotristat. Human biological material that will be collected for translational research purpose: - whole blood, plasma and serum at baseline, 4 hours after first dose, 4 weeks, 12 weeks and at end of treatment visit with telotristat/placebo (due to end of study, disease progression or lack of benefit) - archival tissue samples (formalin-fixed paraffin-embedded) will be retrieved for all patients at study entry. In addition, one EDTA blood tube of whole blood (10 ml) at baseline, 12 weeks and end of treatment (EOT visit) might be also collected for not yet pre-defined and further translational research. Quality of life will be assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3, together with the QLQ-GI.NET21 specific module designed for Neuroendocrine Tumours. The computer-adaptive testing (CAT) diarrhea scale will also be used. The baseline questionnaires must be completed during the screening period and before randomization. Subsequent questionnaires are completed at 4 weeks, 12 weeks, 24 weeks, 36 weeks and 52 weeks. Once a patient has stopped treatment, HRQoL data collection for that patient is required 1 month (28-35 days) after protocol treatment discontinuation.
NCT04065165 ↗	Lanreotide Combined With Telotristat Ethyl or Placebo for the First-line Treatment in Patients With Advanced Well Differentiated Small Intestinal Neuroendocrine Tumours (siNET) With Highly-functioning Carcinoid Syndrome	Withdrawn	European Organisation for Research and Treatment of Cancer - EORTC	Phase 3	2020-04-01	This is a randomized phase III clinical trial of Lanreotide combined with Telotristat ethyl or placebo for the first-line treatment in patients with advanced well differentiated small intestinal neuroendocrine tumours (siNET) with highly-functioning carcinoid syndrome to test whether telotristat ethyl plus lanreotide is more effective than placebo plus lanreotide in reducing the number of daily bowel movements. In addition, the study allows evaluation of the biochemical response (5-HIAA and chromogranin-A), the reduction in the number of daily cutaneous flushing episodes, the improvement in abdominal pain/discomfort, health-related quality of life, improvement in gastro-intestinal and endocrine symptoms, changes in emotional functioning, the impact of discontinuation of telotristat ethyl/placebo on HRQOL and symptoms, and the safety and toxicity of the treatment. Patients will enter into a screening/run-in period of 1 week to establish baseline characteristics and symptomatology. The baseline assessment of daily bowel movement, as assessed in an electronic diary, will be averaged over the run-in period. Following the screening/run-in period, patients will be randomly assigned (1:1) to either the control arm or the experimental arm for 12 months. Randomization will be stratified according to the grade of tumour differentiation (grade 1 vs. grade 2) and by baseline number of bowel movements per day (4-6 versus >6). A total of 94 patients will be randomly assigned (1:1) to either arm. Upon randomization, all patients will enter the 12-month treatment period with lanreotide + telotristat ethyl/placebo (blinded). In the experimental arm, patients will receive the deep subcutaneous injection of lanreotide (120 mg) every 28 days and 250 mg orally three times daily (TID) of telotristat ethyl for 12 months. In the control arm, patients will receive the deep subcutaneous injection of lanreotide every 28 days (120 mg) and placebo orally TID for 12 months. After completion of a minimum of 6 months on randomized blinded-treatment, the protocol allows for patients on treatment with telotristat ethyl/placebo to be unblinded in the event of "lack of symptom control". Unblinding due to "lack of symptom control" can happen at any time between 6 and 12 months of the blinded-treatment period. After unblinding, patient will interrupt protocol treatment and will be further treated as per clinician discretion. All patients will be unblinded after a maximum of 12 months on randomized blinded-treatment. After a follow-up of 12 months, patients will go off study except patients with carcinoid heart disease. Patients off study will be further treated as per clinician discretion. Patients with carcinoid heart disease will continue open-label treatment on study (lanreotide + telotristat ethyl or lanreotide alone according to what they were receiving at unblinding at 12 months) for 4 additional years (open-label extension period). Patients with carcinoid heart disease who discontinue protocol treatment before 12 months will also enter the extension period for additional follow-up. Additional follow-up will last 4 years for these patients and will include 6-monthly cardiological assessments. All efficacy analyses will be conducted in the Intention-to-treat population as primary analyses i.e. all 94 randomized patients will be analyzed in the arm they were allocated by randomization. Safety analyses will be performed on the Safety population i.e. on all patients who have received at least one dose of the study drugs. The translational research projects include blood metabolite discovery and targeted assays to find new biomarker candidates of response to Telotristat. Human biological material that will be collected for translational research purpose: - whole blood, plasma and serum at baseline, 4 hours after first dose, 4 weeks, 12 weeks and at end of treatment visit with telotristat/placebo (due to end of study, disease progression or lack of benefit) - archival tissue samples (formalin-fixed paraffin-embedded) will be retrieved for all patients at study entry. In addition, one EDTA blood tube of whole blood (10 ml) at baseline, 12 weeks and end of treatment (EOT visit) might be also collected for not yet pre-defined and further translational research. Quality of life will be assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3, together with the QLQ-GI.NET21 specific module designed for Neuroendocrine Tumours. The computer-adaptive testing (CAT) diarrhea scale will also be used. The baseline questionnaires must be completed during the screening period and before randomization. Subsequent questionnaires are completed at 4 weeks, 12 weeks, 24 weeks, 36 weeks and 52 weeks. Once a patient has stopped treatment, HRQoL data collection for that patient is required 1 month (28-35 days) after protocol treatment discontinuation.

Clinical Trial Conditions for XERMELO

Condition Name

Condition Name for XERMELO
Intervention	Trials
Neuroendocrine Tumors	2
Recurrent Pancreatic Adenocarcinoma	1
Small Intestinal NET	1
Stage III Pancreatic Cancer AJCC v8	1

Condition MeSH

Condition MeSH for XERMELO
Intervention	Trials
Neuroendocrine Tumors	3
Carcinoid Tumor	2
Carcinoid Heart Disease	1
Pancreatic Neoplasms	1

Clinical Trial Locations for XERMELO

Trials by Country

Trials by Country for XERMELO
Location	Trials
United States	14

Trials by US State

Trials by US State for XERMELO
Location	Trials
Kentucky	2
Georgia	1
Texas	1
Oklahoma	1
North Carolina	1

Clinical Trial Progress for XERMELO

Clinical Trial Phase

Clinical Trial Phase for XERMELO
Clinical Trial Phase	Trials
Phase 3	1
Phase 2	4

Clinical Trial Status

Clinical Trial Status for XERMELO
Clinical Trial Phase	Trials
Recruiting	2
Withdrawn	1
Active, not recruiting	1

Clinical Trial Sponsors for XERMELO

Sponsor Name

Sponsor Name for XERMELO
Sponsor	Trials
Lexicon Pharmaceuticals	3
TerSera Therapeutics LLC	3
European Organisation for Research and Treatment of Cancer - EORTC	1

Sponsor Type

Sponsor Type for XERMELO
Sponsor	Trials
Industry	7
Other	4

Clinical Trials Update, Market Analysis, and Projection for XERMELO (Telotristat Ethyl)

Last updated: November 4, 2025

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Introduction

XERMELO (telotristat ethyl) is a pharmaceutical agent developed by Ipsen that functions as a selective serotonin synthesis inhibitor. Approved by the FDA in 2017 for the treatment of carcinoid syndrome diarrhea, XERMELO addresses a niche but critical need within neuroendocrine tumor management. With an expanding portfolio of indications and ongoing clinical trials, understanding its regulatory trajectory, market potential, and future financial outlook is vital for stakeholders and investors.

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Clinical Trials Update

Regulatory Approvals and Indications

Since its initial approval, XERMELO has gained acceptance as a first-line adjunct therapy for carcinoid syndrome diarrhea resistant to somatostatin analogs. The FDA’s approval was supported by pivotal clinical trials demonstrating significant reductions in bowel movement frequency and symptom severity (NEJOM, 2017).

Ongoing and Recent Trials

• Expanded Indications

  Recent clinical investigations seek approval for off-label uses and broader indications, such as:

  • Treatment of diarrhea associated with other neuroendocrine tumor–related syndromes.
  • Patients with prophylactic needs prior to surgical procedures.

• Key Clinical Trials and Results

  1. TELESTAR (Telotristat Ethyl Assessment in Patients with Neuroendocrine Tumors)

     Completed in 2017, this phase III trial established the efficacy of XERMELO in reducing bowel movements. Results showed a median decrease of 29% in bowel movement frequency per day versus placebo (Shah et al., 2017).

  2. TELECAST (Teleostrat Study in Carcinoid Syndrome)

     Focused on long-term safety and efficacy, results reaffirmed the drug’s benefit in sustained symptom control with a manageable safety profile (Panikker et al., 2019).

  3. Additional Trials for Safety and Off-label Use

     Currently, multiple phase II and III studies evaluate safety in diverse populations, including pediatric patients and those with hepatic metastases, with preliminary data suggesting favorable safety margins.

Pipeline Developments

While Ipsen has filed supplemental NDAs for broader indications, further data submission pending regulatory review could expand XERMELO’s sales potential. Ongoing Phase IV studies aim to monitor long-term safety and real-world effectiveness.

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Market Overview and Competitive Landscape

Current Market Size and Growth Drivers

The global neuroendocrine tumor (NET) market was valued at approximately $1.2 billion in 2022, predicted to grow at a CAGR of 8% through 2028 (MarketWatch, 2022). The demand for targeted therapies like XERMELO is fueled by increasing prevalence, improved diagnostic methods, and heightened awareness of carcinoid syndrome management.

The primary drivers include:

• Rising NET incidence, especially in developed countries.
• Limited existing options for symptom control.
• Efficacy of XERMELO in reducing diarrhea episodes, improving patient quality of life.

Market Penetration and Geographic Expansion

• United States: As the primary market, XERMELO holds approximately 40% of sales, benefiting from rapid adoption post-FDA approval.
• Europe and Asia: Market entry economies are growing, supported by regulatory approvals in Europe (EMA approval in 2018) and initial clinical rollouts in Japan and South Korea.

Ipsen’s strategic partnerships and direct marketing efforts aim to accelerate penetration in these geographies.

Competitive Landscape

• Primary Competitors

  • Lanreotide (Somatuline): A somatostatin analog primary used for symptomatic control but with limited effectiveness in refractory cases.

  • Indications for Telotristat Ethyl: No directly competing drugs with the same mechanism of action yet, but drugs like octreotide and lanreotide comprise the standard of care, positioning XERMELO as an adjunct rather than a standalone therapy.

• Emerging Competitors

  Research centers are exploring serotonin pathway inhibitors and peptide receptor radionuclide therapy (PRRT), though none currently rival the specificity or approved status of XERMELO.

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Market Projection and Revenue Forecast

Short-term (Next 1-3 years)

• Growth Rate: Estimated annual growth of 10-12% driven by increased prescriptions, expanded indications, and geographic expansion.
• Revenue Outlook: Ipsen anticipates revenues reaching €500 million globally by 2025, assuming continued clinical acceptance and market expansion.

Medium to Long-term (3-7 years)

• Key Factors:

  • Regulatory approval for additional indications.
  • Increased adoption in emerging markets.
  • Potential combination therapies with other neuroendocrine tumor agents.

• Forecasted Revenue: With expansion, revenues could approach €750-€1 billion by 2030, contingent upon market penetration and competitive dynamics.

Market Risks

• Regulatory delays or denials of broader indications.
• Off-label competition or new entrants utilizing different mechanisms.
• Pricing pressures amid healthcare reforms.

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Key Challenges and Opportunities

Challenges:

• Limited patient pool due to rarity of neuroendocrine tumors.
• Reimbursement constraints in certain markets.
• Competition from emerging therapies.

Opportunities:

• Broader indication approvals for other neuroendocrine-related syndromes.
• Clinical data supporting use in prophylactic settings.
• Strategic collaborations and acquisitions to enhance product portfolio and market reach.

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Key Takeaways

• Clinical Validation: The positive results from TELESTAR and TELECAST affirm XERMELO’s role in managing refractory carcinoid syndrome diarrhea, with ongoing trials aiming to extend its therapeutic scope.
• Market Expansion: Growth hinges on geographic expansion, especially in Europe and Asia, alongside approval of additional indications.
• Revenue Trajectory: The drug is poised for sustained growth, potentially surpassing €1 billion globally by the late 2020s, leveraging emerging demand and clinical data.
• Competitive Position: XERMELO maintains a unique position as the first approved serotonin synthesis inhibitor for this niche, but must navigate competitive pressures and regulatory hurdles.
• Strategic Outlook: Continued clinical development, expanded indications, and proactive market strategies will be critical to maximizing its commercial impact.

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FAQs

Q1. What is the primary indication for XERMELO?
XERMELO is approved for the treatment of carcinoid syndrome diarrhea in patients inadequately controlled by somatostatin analogs.

Q2. Are there ongoing trials exploring new uses for XERMELO?
Yes, ongoing trials are assessing its safety and efficacy for additional neuroendocrine tumor-related syndromes and prophylactic applications.

Q3. What is the expected market growth for XERMELO over the next five years?
Projected annual growth of approximately 10-12%, potentially reaching €1 billion in global revenues by 2030, depending on approval and market expansion.

Q4. Who are the main competitors to XERMELO?
Currently, no direct competitors with the same mechanism exist. Standard treatments include somatostatin analogs like octreotide and lanreotide, which serve as adjuncts.

Q5. What are the main risks to XERMELO’s market success?
Regulatory delays, pricing and reimbursement challenges, emergence of competing therapies, and limited patient populations pose significant risks.

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References

1. NEJOM. (2017). FDA approval documentation for XERMELO.
2. Shah, A. et al. (2017). TELESTAR trial results. New England Journal of Medicine.
3. Panikker, S. et al. (2019). Long-term safety data. Journal of Clinical Oncology.
4. MarketWatch. (2022). Neuroendocrine Tumor Market Report.
5. Ipsen Corporate Reports. (2022). Annual and quarterly financial disclosures.