CLINICAL TRIALS PROFILE FOR NETUPITANT; PALONOSETRON HYDROCHLORIDE

All Clinical Trials for netupitant; palonosetron hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02517021 ↗	A Safety Study of Intravenous Pro-Netupitant and Palonosetron Combination for the Prevention of Nausea and Vomiting	Completed	PSI CRO	Phase 3	2015-11-01	NEPA-15-18 is a clinical study assessing safety of pro-netupitant and palonosetron, two antiemetic drugs, given with oral dexamethasone. The objective of the study is to evaluate if pro-netupitant and palonosetron are safe when administered to prevent nausea and vomiting after administration of repeated cycles of chemotherapy.
NCT02517021 ↗	A Safety Study of Intravenous Pro-Netupitant and Palonosetron Combination for the Prevention of Nausea and Vomiting	Completed	PSI CRO AG	Phase 3	2015-11-01	NEPA-15-18 is a clinical study assessing safety of pro-netupitant and palonosetron, two antiemetic drugs, given with oral dexamethasone. The objective of the study is to evaluate if pro-netupitant and palonosetron are safe when administered to prevent nausea and vomiting after administration of repeated cycles of chemotherapy.
NCT01376297 ↗	A Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting	Completed	Parexel	Phase 3	2011-07-01	NETU-10-29 is a clinical study assessing safety of netupitant and palonosetron, two antiemetic drugs, both given with oral dexamethasone. The objective of the study is to evaluate if netupitant and palonosetron are safe when administered to prevent nausea and vomiting after administration of repeated cycles of chemotherapy.
NCT01376297 ↗	A Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting	Completed	Helsinn Healthcare SA	Phase 3	2011-07-01	NETU-10-29 is a clinical study assessing safety of netupitant and palonosetron, two antiemetic drugs, both given with oral dexamethasone. The objective of the study is to evaluate if netupitant and palonosetron are safe when administered to prevent nausea and vomiting after administration of repeated cycles of chemotherapy.
NCT01339260 ↗	An Efficacy and Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting	Completed	Parexel	Phase 3	2011-04-01	NETU-08-18 is a two-arm clinical study assessing efficacy and safety of a single oral dose of netupitant and palonosetron, two antiemetic drugs, versus oral palonosetron, both given with oral dexamethasone. The objective of the study is to demonstrate that netupitant and palonosetron are more effective than palonosetron alone, to prevent nausea and vomiting induced by moderately emetogenic cancer chemotherapy after administration of repeated cycles of chemotherapy.
NCT01339260 ↗	An Efficacy and Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting	Completed	Helsinn Healthcare SA	Phase 3	2011-04-01	NETU-08-18 is a two-arm clinical study assessing efficacy and safety of a single oral dose of netupitant and palonosetron, two antiemetic drugs, versus oral palonosetron, both given with oral dexamethasone. The objective of the study is to demonstrate that netupitant and palonosetron are more effective than palonosetron alone, to prevent nausea and vomiting induced by moderately emetogenic cancer chemotherapy after administration of repeated cycles of chemotherapy.

Clinical Trial Conditions for netupitant; palonosetron hydrochloride

Condition Name

Condition Name for netupitant; palonosetron hydrochloride
Intervention	Trials
Chemotherapy-induced Nausea and Vomiting	9
Malignant Neoplasm	2
Chemotherapy-induced Nausea and Vomiting (CINV)	1
Head and Neck Squamous Cell Carcinoma (HNSCC)	1

Condition MeSH

Condition MeSH for netupitant; palonosetron hydrochloride
Intervention	Trials
Vomiting	15
Nausea	11
Breast Neoplasms	3
Neoplasms	2

Clinical Trial Locations for netupitant; palonosetron hydrochloride

Trials by Country

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Trials by Country for netupitant; palonosetron hydrochloride
Location	Trials
United States	72
Italy	7
Ukraine	4
Poland	3
Serbia	3

Trials by US State

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−

Trials by US State for netupitant; palonosetron hydrochloride
Location	Trials
South Carolina	5
Ohio	5
Florida	4
California	4
New York	4

Clinical Trial Progress for netupitant; palonosetron hydrochloride

Clinical Trial Phase

Clinical Trial Phase for netupitant; palonosetron hydrochloride
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	6
Phase 2/Phase 3	2

Clinical Trial Status

Clinical Trial Status for netupitant; palonosetron hydrochloride
Clinical Trial Phase	Trials
Completed	7
Recruiting	6
Active, not recruiting	2

Clinical Trial Sponsors for netupitant; palonosetron hydrochloride

Sponsor Name

Sponsor Name for netupitant; palonosetron hydrochloride
Sponsor	Trials
Helsinn Healthcare SA	8
National Cancer Institute (NCI)	3
Consorzio Oncotech	2

Sponsor Type

Sponsor Type for netupitant; palonosetron hydrochloride
Sponsor	Trials
Other	19
Industry	13
NIH	3

Netupitant and Palonosetron Hydrochloride: Clinical Trials, Market Analysis, and Projections

Introduction

Netupitant and palonosetron hydrochloride, marketed under the brand name Akynzeo, is a fixed-dose combination (FDC) of a neurokinin-1 (NK1) receptor antagonist and a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, respectively. This combination is designed to prevent acute and delayed nausea and vomiting associated with highly emetogenic cancer chemotherapy.

Mechanism of Action

The mechanism of action of Akynzeo involves the inhibition of two key pathways that trigger nausea and vomiting. Netupitant selectively antagonizes the human substance P/neurokinin 1 (NK1) receptors, while palonosetron is a potent 5-HT3 receptor antagonist. This dual action effectively blocks the vomiting reflex initiated by chemotherapy-induced release of serotonin and substance P[1].

Clinical Trials

Efficacy and Safety

Clinical trials have demonstrated the superior efficacy of the netupitant and palonosetron FDC over palonosetron alone in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV). In the pivotal NETU-07-07 trial, the combination of 300mg netupitant and 0.50mg palonosetron showed significant superiority in achieving complete response (CR) rates compared to palonosetron alone. The CR rates for the combination were 87.4%, 87.6%, and 89.6% for the 100mg, 200mg, and 300mg netupitant doses, respectively, versus 76.5% for palonosetron alone[3].

Multiple-Cycle Efficacy

The NETU-08-18 trial, which evaluated the efficacy of Akynzeo over multiple chemotherapy cycles, further reinforced its superiority. The study showed that the netupitant/palonosetron FDC maintained its efficacy across multiple treatment cycles, with CR rates of 74.3% in the overall phase, compared to 66.6% for palonosetron alone[3].

Pediatric Studies

Pediatric clinical development for Akynzeo has been ongoing, with several studies aimed at evaluating the safety and efficacy in children aged 0 to 17 years undergoing emetogenic chemotherapy. These studies include pharmacokinetic and pharmacodynamic assessments, as well as safety and tolerability evaluations. However, the pediatric clinical development has faced challenges, leading to slower progress than anticipated[4].

Market Analysis

Market Size and Growth

The global netupitant and palonosetron hydrochloride capsules market has been experiencing significant growth. As of 2023, the market was valued at approximately USD 1.57 billion and is projected to grow at a Compound Annual Growth Rate (CAGR) of about 10.5% from 2024 to 2033, reaching an estimated market size of USD 4.17 billion by 2033[2].

Market Drivers

The primary drivers of this market include the increasing prevalence of cancer and the growing number of patients undergoing chemotherapy. According to the World Health Organization (WHO), cancer is the second leading cause of death globally, with an estimated 9.6 million deaths in 2018. The demand for effective antiemetic drugs to manage CINV is also a key driver, with Akynzeo offering superior efficacy and a favorable safety profile[2].

Regional Analysis

The market is segmented into North America, Europe, Asia-Pacific, Latin America, and Middle East & Africa. North America, particularly the United States, is the largest market due to the high prevalence of cancer and well-established healthcare infrastructure. Europe is the second-largest market, while the Asia-Pacific region is expected to witness the highest growth due to increasing cancer prevalence, rising healthcare expenditure, and growing awareness about CINV management[2].

Market Opportunities

Personalized Medicine

The increasing focus on personalized medicine and the use of pharmacogenetic testing and biomarkers present opportunities for growth. These tools can help identify patients at high risk of CINV and guide the selection of appropriate antiemetic prophylaxis, potentially improving treatment outcomes[2].

Novel Formulations

The development of novel formulations and drug delivery systems, such as transdermal patches and oral suspensions, can enhance patient adherence and treatment outcomes. These innovations can also make the drug more accessible and affordable in emerging economies[2].

Emerging Markets

The growing demand for antiemetic drugs in emerging economies like China, India, and Brazil offers significant opportunities. Manufacturers can expand their distribution networks, collaborate with local partners, and develop affordable formulations to tap into these markets[2].

Safety and Adverse Reactions

QT Interval Prolongation

Akynzeo contains a 5-HT3 receptor antagonist, and caution is advised when used concomitantly with medicinal products that increase the QT interval or in patients with conditions that may lead to QT prolongation, such as electrolyte abnormalities or congestive heart failure[1].

Common Adverse Reactions

While netupitant itself does not have common adverse reactions, palonosetron has been associated with cases of constipation, eye swelling, dyspnea, and myalgia. Rare but serious adverse reactions include anaphylaxis and anaphylactoid reactions[1].

Future Outlook

The future outlook for the netupitant and palonosetron hydrochloride capsules market is promising. The increasing prevalence of cancer, growing demand for effective antiemetic drugs, and advancements in personalized medicine are expected to drive market growth. The Asia-Pacific region is anticipated to witness the highest growth due to its increasing cancer incidence and rising healthcare expenditure[2].

Key Takeaways

• Efficacy: Netupitant and palonosetron hydrochloride combination has shown superior efficacy in preventing acute and delayed CINV.
• Market Growth: The global market is projected to grow at a CAGR of 10.5% from 2024 to 2033.
• Market Drivers: Increasing cancer prevalence and demand for effective antiemetic drugs are key drivers.
• Regional Growth: Asia-Pacific region expected to witness the highest growth.
• Safety: Caution advised regarding QT interval prolongation and rare but serious adverse reactions.

FAQs

What is the mechanism of action of Akynzeo?

Akynzeo works by inhibiting the NK1 and 5-HT3 receptors, which are involved in the vomiting reflex triggered by chemotherapy-induced release of substance P and serotonin.

What are the key clinical trial findings for Akynzeo?

Clinical trials have shown that the netupitant and palonosetron combination is superior to palonosetron alone in preventing acute and delayed CINV, with high complete response rates maintained across multiple chemotherapy cycles.

What are the primary market drivers for Akynzeo?

The increasing prevalence of cancer and the growing demand for effective antiemetic drugs are the primary drivers of the market.

Which region is expected to witness the highest growth in the Akynzeo market?

The Asia-Pacific region is expected to witness the highest growth due to increasing cancer incidence, rising healthcare expenditure, and growing awareness about CINV management.

What are the potential safety concerns associated with Akynzeo?

Caution is advised regarding the use of Akynzeo in patients with conditions that may lead to QT interval prolongation, and rare but serious adverse reactions such as anaphylaxis and anaphylactoid reactions have been reported.

Sources

1. European Medicines Agency. Akynzeo, INN-netupitant & palonosetron hydrochloride. [PDF]
2. Data Horizon Research. Netupitant And Palonosetron Hydrochloride Capsules Market Size.
3. FDA. 205718Orig1s000 - accessdata.fda.gov.
4. FDA. Akynzeo® (netupitant-palonosetron hydrochloride) Capsules. [PDF]