ENTRECTINIB - Generic Drug Details

What are the generic drug sources for entrectinib and what is the scope of freedom to operate?

Entrectinib is the generic ingredient in one branded drug marketed by Genentech Inc and is included in two NDAs. There are fourteen patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Entrectinib has one hundred and twenty-three patent family members in thirty countries.

One supplier is listed for this compound.

Summary for ENTRECTINIB

International Patents:	123
US Patents:	14
Tradenames:	1
Applicants:	1
NDAs:	2
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	59
Clinical Trials:	32
Patent Applications:	986
What excipients (inactive ingredients) are in ENTRECTINIB?	ENTRECTINIB excipients list
DailyMed Link:	ENTRECTINIB at DailyMed

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for ENTRECTINIB

Constraining patent/regulatory exclusivity:

10,398,693

Dosage:

CAPSULE;ORAL

Constraining patent/regulatory exclusivity:

TREATMENT OF PEDIATRIC PATIENTS OLDER THAN 1 MONTH UP TO 12 YEARS OF AGE WITH SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION, AS DETECTED BY AN FDA-APPROVED TEST WITHOUT A KNOWN ACQUIRED RESISTANCE MUTATION, ARE METASTATIC OR WHERE SURGICAL RESECTION IS LIKELY TO RESULT IN SEVERE MORBIDITY, AND HAVE PROGRESSED FOLLOWING TREATMENT OR HAVE NO SATISFACTORY ALTERNATIVE THERAPY

Dosage:

PELLETS;ORAL

^*The generic entry opportunity date is the latter of the last compound-claiming patent and the last regulatory exclusivity protection. Many factors can influence early or later generic entry. This date is provided as a rough estimate of generic entry potential and should not be used as an independent source.

Recent Clinical Trials for ENTRECTINIB

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Hunan Province Tumor Hospital	Phase 1/Phase 2
Cancer Research UK	Phase 2/Phase 3
Royal Marsden NHS Foundation Trust	Phase 2/Phase 3

See all ENTRECTINIB clinical trials

Anatomical Therapeutic Chemical (ATC) Classes for ENTRECTINIB

L01EX	Other protein kinase inhibitors
L01E	PROTEIN KINASE INHIBITORS
L01	ANTINEOPLASTIC AGENTS
L	Antineoplastic and immunomodulating agents

US Patents and Regulatory Information for ENTRECTINIB

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-001	Aug 15, 2019		RX	Yes	No
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-001	Aug 15, 2019		RX	Yes	No	10,561,651
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-002	Aug 15, 2019		RX	Yes	Yes	9,085,565		Y	Y
Genentech Inc	ROZLYTREK	entrectinib	CAPSULE;ORAL	212725-002	Aug 15, 2019		RX	Yes	Yes	9,649,306

EU/EMA Drug Approvals for ENTRECTINIB

Company	Drugname	Inn	Product Number / Indication	Status	Generic	Biosimilar	Orphan	Marketing Authorisation	Marketing Refusal
Roche Registration GmbH	Rozlytrek	entrectinib	EMEA/H/C/004936 Rozlytrek as monotherapy is indicated for the treatment of adult and paediatric patients 12 years of age and older with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion,who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, andwho have not received a prior NTRK inhibitorwho have no satisfactory treatment options.Rozlytrek as monotherapy is indicated for the treatment of adult patients with ROS1 positive, advanced non small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.	Authorised	no	no	no	2020-07-31

International Patents for ENTRECTINIB

Country	Patent Number	Title	Estimated Expiration
European Patent Office	2176231	DÉRIVÉS D'INDAZOLE SUBSTITUÉS ACTIFS COMME INHIBITEURS DE KINASES (SUBSTITUTED INDAZOLE DERIVATIVES ACTIVE AS KINASE INHIBITORS)
Mexico	2016010519	MOLECULAS PARA ADMINISTRACION A CELULAS CANCEROSAS MUTANTES ROS1. (COMPOUNDS FOR TREATING PATIENTS WITH ROS1 MUTANT CANCER CELLS.)
Israel	260297	תהליך להכנת n-[5-(5,3-דיפלואורו-בנזיל)-h1-אינדאזול-3-איל]-4-(4-מתיל-פיפראזין-1-איל)-2-(טטראהידרו-פיראן-4-אילאמינו)-בנזאמיד (Process for the preparation of n-[5-(3,5-difluoro-benzyl)-1h-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide)
Eurasian Patent Organization	201691151	СОЕДИНЕНИЯ ДЛЯ ЛЕЧЕНИЯ ПАЦИЕНТОВ С ROS1-МУТАНТНЫМИ РАКОВЫМИ КЛЕТКАМИ

Supplementary Protection Certificates for ENTRECTINIB

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
3107541	122021000032	Germany		PRODUCT NAME: ENTRECTINIB IN ALLEN DEM GRUNDPATENT ZUGRUNDE LIEGENDEN FORMEN; REGISTRATION NO/DATE: EU/1/20/1460 20200731
2176231	132020000000164	Italy		PRODUCT NAME: ENTRECTINIB O SUOI ISOMERI, TAUTOMERI O SALI FARMACEUTICAMENTE ACCETTABILI(ROZLYTREK); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/20/1460, 20200803
2176231	46/2020	Austria		PRODUCT NAME: ENTRECTINIB ODER ISOMERE, TAUTOMERE ODER PHARMAZEUTISCH ANNEHMBARE SALZE DAVON; REGISTRATION NO/DATE: EU/1/20/1460 (MITTEILUNG) 20200803
2176231	2020C/551	Belgium		PRODUCT NAME: ENTRECTINIB OF ISOMEREN, TAUTOMEREN OF FARMACEUTISCH AANVAARDBARE ZOUTEN DAARVAN; AUTHORISATION NUMBER AND DATE: EU/1/20/1460 20200803

ENTRECTINIB Market Analysis and Financial Projection

Market Dynamics and Financial Trajectory for Entrectinib (Rozlytrek)

Introduction

Entrectinib, marketed as Rozlytrek, is a targeted therapy approved by the FDA for the treatment of adult and pediatric patients with solid tumors harboring NTRK gene fusions or ROS1 fusions, particularly in non-small cell lung cancer (NSCLC). Here, we delve into the market dynamics and financial trajectory of this drug.

Clinical Efficacy and Approval

Entrectinib has demonstrated significant clinical efficacy in patients with NTRK and ROS1 fusion-positive tumors. For ROS1-positive NSCLC, entrectinib showed an overall response rate (ORR) of 77% and a median duration of response of 24.6 months[2].

The FDA granted accelerated approval to entrectinib in August 2019 for patients 12 years and older with solid tumors having NTRK fusions, and later extended this approval to include pediatric patients as young as 1 month old[5].

Market Size and Growth

The global market for TRK inhibitors, which includes entrectinib, is projected to surpass $2 billion by 2026. This growth is driven by several factors:

• Increasing Prevalence of Cancer: The rising incidence of cancer globally is a significant driver for the demand of targeted therapies like entrectinib[4].
• Research and Development: Ongoing clinical trials and the development of new TRK inhibitors are expected to enhance the market size[4].
• Government Initiatives and Awareness: Increased awareness about the availability of these drugs and government initiatives to support cancer research and treatment are also contributing to market growth[4].

Competitive Landscape

Entrectinib competes in the TRK inhibitor market alongside another approved drug, larotrectinib (Vitrakvi). Both drugs have shown promising results in treating NTRK fusion-positive solid tumors, including those with central nervous system (CNS) metastases[4].

Cost-Effectiveness and Pricing

The cost-effectiveness of entrectinib is a critical factor in its market dynamics. According to the CADTH review, the incremental cost-effectiveness ratio (ICER) for entrectinib compared to second-line treatment options exceeds $550,000 per quality-adjusted life-year (QALY) gained, and over $10 million per QALY when including the costs of patient identification. However, for specific indications with high NTRK prevalence, price reductions could make entrectinib cost-effective at a threshold of $50,000 per QALY gained[1].

The cost of entrectinib is significant, with a monthly cost of $8,007.72 for adult patients based on the recommended dosing of 600 mg once daily[1].

Safety and Adverse Effects

While entrectinib has shown promising efficacy, it also comes with a range of adverse effects. Common side effects include pyrexia, constipation, increased weight, vomiting, diarrhea, and nausea. Serious adverse events, such as nervous system disorders and cardiac disorders, have also been reported[2][5].

Patient and Clinician Feedback

Patients and clinicians have highlighted the importance of biomarker testing for identifying eligible patients. Patients have reported improved quality of life, tumor reduction, and reduced side effects with entrectinib treatment. However, some patients have expressed the need for earlier biomarker screening and treatment for brain metastases[1].

Future Outlook

The future outlook for entrectinib is promising, given its efficacy in treating NTRK and ROS1 fusion-positive tumors. Ongoing clinical trials and the expansion of its approval to pediatric patients are expected to further boost its market presence.

Key Trends and Drivers

• Increasing Awareness: Growing awareness about the availability and benefits of TRK inhibitors is expected to drive market growth.
• Government Support: Government initiatives to support cancer research and treatment will continue to play a crucial role.
• Clinical Trials: Ongoing and future clinical trials will provide more data on the long-term efficacy and safety of entrectinib, potentially expanding its indications.
• Market Competition: The introduction of new TRK inhibitors could increase competition, but the unique profile of entrectinib, especially its brain-penetrating capability, positions it strongly in the market[2][4].

Challenges

Despite the positive outlook, there are challenges to consider:

• Cost and Accessibility: The high cost of entrectinib and the need for biomarker testing could limit accessibility for some patients.
• Uncertainty in Clinical Effectiveness: The CADTH review highlighted substantial uncertainty regarding the clinical effectiveness of entrectinib across different tumor types, which could impact its adoption[1].

Key Takeaways

• Clinical Efficacy: Entrectinib has shown significant efficacy in treating NTRK and ROS1 fusion-positive tumors.
• Market Growth: The global TRK inhibitor market is expected to surpass $2 billion by 2026.
• Cost-Effectiveness: The drug's high cost is a significant factor, but price reductions could make it cost-effective for specific indications.
• Safety and Adverse Effects: Entrectinib comes with a range of adverse effects, necessitating careful patient monitoring.
• Future Outlook: Ongoing clinical trials and expanded approvals are expected to boost its market presence.

Frequently Asked Questions

Q: What is entrectinib used for? A: Entrectinib is used for the treatment of adult and pediatric patients with solid tumors that have NTRK gene fusions or ROS1 fusions, particularly in non-small cell lung cancer (NSCLC)[2][5].

Q: How effective is entrectinib? A: Entrectinib has shown an overall response rate of 77% and a median duration of response of 24.6 months in patients with ROS1-positive NSCLC[2].

Q: What are the common side effects of entrectinib? A: Common side effects include pyrexia, constipation, increased weight, vomiting, diarrhea, and nausea. Serious adverse events such as nervous system disorders and cardiac disorders have also been reported[2][5].

Q: How much does entrectinib cost? A: The monthly cost of entrectinib is approximately $8,007.72 for adult patients based on the recommended dosing[1].

Q: Is entrectinib cost-effective? A: The cost-effectiveness of entrectinib varies by indication. While it is not cost-effective at current prices for many indications, price reductions could make it cost-effective for specific tumor types with high NTRK prevalence[1].

Sources

1. CADTH Review: Pharmacoeconomic Review - Entrectinib (Rozlytrek) - NCBI Bookshelf.
2. Onclive: Published Entrectinib Data Demonstrate Encouraging Responses in ROS1 NSCLC.
3. Biospace: TRK Inhibitors Market Size, Drug Sales & Clinical Trials Insight 2026.
4. Cancer Network: FDA Approves Entrectinib for Pediatric Solid Tumors.