A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects 12 Months of Age and Older

The purpose of the study is to evaluate the long-term safety, tolerability, efficacy, and pharmacodynamics (PD) of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA).

Start Date01 Oct 2024

Sponsor / Collaborator

Vertex Pharmaceuticals, Inc.

NCT05882357 / RecruitingPhase 3

A Phase 3, Open-label Study Evaluating the Pharmacokinetics, Safety, and Tolerability of Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects 12 to Less Than 24 Months of Age

This study will evaluate the pharmacokinetics (PK), safety, tolerability, pharmacodynamics (PD), and efficacy of ELX/TEZ/IVA in CF subjects 12 to less than (<) 24 months of age.

Start Date27 Jun 2023

Sponsor / Collaborator

Vertex Pharmaceuticals, Inc.

NCT06191640 / RecruitingNot ApplicableIIT

Sinus Disease in Young Children With Cystic Fibrosis

This is a prospective, observational study examining the impact of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators on chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) in young children with cystic fibrosis (YCwCF). This study involves two groups: children 2-8 years old, inclusive at initial visit, receiving highly effective modulator therapy (HEMT), and a control group of children 2-8 years old, inclusive at initial visit, not receiving HEMT. Outcomes will include sinus magnetic resonance imaging (MRI) scans, olfactory tests, and quality of life surveys obtained over a two-year period.

Start Date12 Apr 2023

Sponsor / Collaborator

University of California, Los Angeles

[+6]

100 Clinical Results associated with Ivacaftor

100 Translational Medicine associated with Ivacaftor

100 Patents (Medical) associated with Ivacaftor

1,605

Literatures (Medical) associated with Ivacaftor

01 Apr 2024·Journal of affective disorders

Drug-induced depressive symptoms: An update through the WHO pharmacovigilance database

Article

Author: Storck, Wilhelm ; Yrondi, Antoine ; Laforgue, Edouard-Jules ; Li, Julien ; Zelmat, Yoann ; Sommet, Agnès ; Balcerac, Alexander ; Montastruc, François

BACKGROUND:

Depression is a highly incident condition and some drugs have been described as inducing or worsening depression. However, literature on this topic is rare and possibly outdated.

METHODS:

We performed disproportionality analyses using VigiBase®, the largest pharmacovigilance database worldwide to identify drugs associated with depression. Then we excluded drugs already known as depressogenic according to American Summary of Product Characteristics (SPC). We then reviewed drug mechanism of action, scientific literature and European SPC for each drug identified to assess a level of plausibility. We measured Reporting Odds Ratio (ROR) statistically significant and superior to 1, suggesting a significant association between a drug and the reporting of depressive symptoms.

RESULTS:

Out of the 5237 drugs extracted on VigiBase®, we have retained 89 new drugs associated with depression. More than half of drugs of interest are from nervous system. Opicapone (ROR: 20.66 95 %CI: 15.62-27.33), and gadoversetamide (ROR 18.62, 95 %CI 9.63-35.95) were the drugs with the highest ROR. Among the 89 drugs, 38 were considered already described such as suvorexant or ivacaftor, 20 likely associated such as anti-migraines drugs or new antipsychotic drugs and 31 potentially associated.

LIMITATIONS:

Pharmacovigilance studies have many inherent limitations, such as under-reporting bias, notoriety effect and protopathic bias. These results are not intended to establish a causal link, only a statistical association.

CONCLUSION:

We found a strong statistical signal and pharmacological plausibility for 58 new depressogenic drugs. This update list of suspected drugs may prove useful for doctors faced with potential cases of drug-induced depression or to stay aware in case. Other studies are needed to confirm the list.

01 Mar 2024·Current reviews in clinical and experimental pharmacology

Cystic Fibrosis Transmembrane Conductance Regulator Protein Modulators in Children and Adolescents with Different CF Genotypes - Systematic Review and Meta-Analysis

Article

Author: Guntipalli, Prathima ; Zakaria, Faiza ; Yousif Hamdan, Alaa Hassan ; Nasr, Ujala ; Zahid, Samina ; Lourdes Pormento, Maria Kezia ; Hasan Rizvi, Syed Asad ; Lawal, Odunayo Susan ; Opiegbe, Adaugo

Objective::

To determine the efficacy of the first triple CFTR protein modulators in children and adolescents with cystic fibrosis.

Methods::

Systematic review and meta-analysis were conducted, following PRISMA guidelines. The following databases were searched extensively: PubMed/Medline, Clinical trials.gov, Google Scholar, Scopus, Embase, and Europe PMC using the keywords: “Ivacaftor”, “Elexacaftor”, “Tezacaftor”, VX_661”, VX_770”, “VX_445”, “cystic fibrosis”. A total of ten randomized clinical trials were included in our analysis. Primary outcomes included: Absolute change in predicted FEV1 from baseline, Absolute change in sweat chloride test from baseline, Absolute change in BMI from baseline, Absolute change in CF-QR from baseline, and Adverse Events.

Results::

Among primary findings, significant absolute change in predictive FEV1 from baseline through 4 weeks favoured the triple CFTR protein modulators. (MD = 11.80, 95% CI = 8.47_15.12, p value = <0.00001); as well as CF_QR score (MD = 0.00, 95% CI = -2.50_2.50, p value = 1.00), and BMI kg/m² change (MD = 16.90, 95% CI = 12.73_21.06, p value = <0.00001). No significant change was noted for CFTR channels activity in the treatment group when compared to placebo or VX_770/VX_661 (MD = -12.57, 95% CI = -94.46_69.32, p value = 0.76).

Conclusion::

In children aged ≥ 6 y old and adolescents with F508del_CFTR mutation, Elexacaftor- Tezacaftor-Ivacaftor tend to be more effective than first-generation therapy, demonstrating promising results by exhibiting significant improvement in lung function, body weight, and respiratory-related quality of life.

01 Mar 2024·European journal of ophthalmology

The efficacy of different anti-vascular endothelial growth factor agents, and dexamethasone implant therapy in patients with serous retinal detachment caused by Irvine-Gass syndrome

Article

Author: Karasu, Buğra ; Kesim, Enes ; Celebi, Ali Rıza Cenk

Purpose:

The aim of this study is to compare the efficacy of intravitreal aflibercept (IVA), bevacizumab (IVB), ranibizumab (IVR), and dexamethasone implant (IVDI) in the treatment of serous retinal detachment (SRD) caused by Irvine-Gass syndrome (IGS).

Design:

Retrospective cohort, comparative study.

Methods and Materials:

The medical records of 128 eyes with no previous history of intravitreal agents in 128 IGS patients with SRD that received IVA, IVB, IVR, and IVDI monotherapy were retrospectively reviewed. The patients were divided into 4 groups, according to treatment. Patients with recurrence and/or were unresponsive following a course of topical steroids and non-steroidal anti-inflammatory drugs (NSAIDs) were included in the study. Best corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and SRD were compared between the 4 treatment groups at baseline, at follow-up months 1, 3, 6, and 12, and at the final follow-up visit.

Results:

Serous retinal detachment completely resolved in 74%, 45.7%, 66.4%, and 40.8% of the eyes at month 1 (P = 0.042), 87%, 50.9%, 75.8%, and 80.9% at month 3 (p = 0.031), 88.9%, 50.4%, 75.7%, 80.2% at month 6 (p = 0.028), 81.7%, 72.8%, 68.7%, 80.1% at month 12 (p = 0.580), and 100%, 66.4%, 87.9%, 93.2% (p = 0.478) at final follow-up visit in the IVA, IVB, IVR, and IVDI groups, respectively. BCVA was significantly better in the IVA group at all follow-up time points (month 1: p < 0.001; month 3: p < 0.001; month 6: p = 0.002; month 12: p = 0.009, final follow-up visit: p < 0.001). CMT was significantly lower in the IVA group at months 3 (p = 0.008), 6 (p = 0.011), and 12 (p = 0.010), and at the final follow-up visit (p < 0.001). Recurrence was observed after a longer period of time and fewer injections were needed in the IVDI and IVA groups (p < 0.05). Resolution of CME was most rapid in the IVA group (p = 0.032).

Conclusion:

All intravitreal agents were effective in terms of visual results in the SRD patients; however, eyes treated with IVA and IVDI required fewer injections, as compared to the eyes treated with IVB and IVR. Furthermore, SRD entirely resolved in all eyes in the IVA group at the final follow-up visit.

News (Medical) associated with Ivacaftor

21 Jun 2024

·www.fiercepharma.com

Vertex clinches Trikafta and other cystic fibrosis drug reimbursement deal in England

Last November, NICE acknowledged in draft guidance the effectiveness of Vertex’s CF cocktails, but the agency stopped short of dubbing the medicines cost-effective. Cystic fibrosis (CF) patients and their families in England can rest a little easier this week, thanks to an extended long-term reimbursement deal inked by Vertex Pharmaceuticals and the country’s National Health Service (NHS). The accord comes after years of back-and-forth in the United Kingdom over the cost of Vertex’s life-saving—yet expensive—CF drugs. Vertex announced the updated reimbursement deal with the NHS on Thursday, which ensures access to the drugmaker’s CF meds Trikafta (known as Kaftrio in the U.K.), Symkevi and Orkambi for all existing and future eligible cystic fibrosis patients in England. It’s expected that similar deals will soon materialize in Wales, Scotland and Northern Ireland, according to the British Broadcasting Corporation (BBC). The agreement comes after the U.K.’s drug cost gatekeeper, the National Institute for Health and Care Excellence (NICE), issued a positive recommendation for Vertex’s roster of CFTR modulators in June. In November 2023, NICE acknowledged in draft guidance the effectiveness of Vertex’s CF cocktails, but the agency stopped short of dubbing the medicines cost-effective. “Even when considering the condition’s severity … the most likely cost-effectiveness estimates for [Trikafta], [Symkevi] and [Orkambi] are above the range that NICE considers an acceptable use of NHS resources,” the government agency said at the time. The situation mirrored a yearslong standoff between Vertex and the NHS over the pricing of Orkambi and other CF drugs that was resolved in 2019 with a four-year government reimbursement deal. Trikafta was added to the scheme in 2020. At the time of NICE’s decision last fall, David Ramsden, CEO of the Cystic Fibrosis Trust, argued that Vertex, NICE and the NHS must “urgently work together to find a solution to make these treatments available for all those who could potentially benefit.” Under the latest deal, patients will also receive access to any future license extensions on Vertex’s CF meds, the company explained in its release. Moreover, Vertex, NICE and the NHS are working on a path towards “rapid access” for Vertex’s next investigational cocktail for CF, which combines vanzacaftor, tezecaftor and deutivacaftor, should the combo therapy pass muster with England’s drug regulator. CF is a genetic condition in which a faulty protein affects the body’s cells, tissues and mucus- and sweat-producing glands. Patients with the disease make thick, sticky mucus that can build up and cause damage or infection to organs like the lungs and pancreas. The most serious and common complications of CF are respiratory in nature, including serious lung infections. Vertex’s flagship drug Trikafta is a combination of elexacaftor, ivacaftor and tezacaftor. It works by helping defective CF transmembrane conductance regulator proteins work more effectively. Vertex’s roster of CF medicines is currently “broadly available” in more than 60 countries, including Australia, France, Italy, Germany, the Republic of Ireland, the Netherlands, Spain and the U.S., the company explained. Meanwhile, another pricing standoff could be brewing between NICE and Vertex on the drugmaker’s CRISPR Therapeutics-partnered gene therapy for sickle cell disease, Casgevy. In draft guidance unveiled in March, the cost watchdog did not endorse Casgevy—which gained its U.K. approval in November 2023—but caveated that it was “exploring further data collection” on the therapy’s effectiveness and a potential commercial arrangement.

Gene Therapy

21 Jun 2024

·www.biospace.com

Vertex Finally Reaches Pricing Deal With England’s NHS for Cystic Fibrosis Drugs

Pictured: Vertex Pharmaceuticals' headquarters in Boston, Massachusetts/iStock, hapabapa Vertex Pharmaceuticals on Thursday announced that it has entered into an extended, long-term reimbursement agreement with England’s National Health Service, granting access to its cystic fibrosis treatments Kaftrio (ivacaftor/tezacaftor/elexacaftor), Symkevi (ezacaftor/ivacaftor) and Orkambi (lumacaftor/ivacaftor). The biotech did not disclose specific details of the deal, only revealing that it would also apply to future license extensions of these drugs. Vertex is working on similar deals in Scotland, Wales and Northern Ireland. Ludovic Fenaux, senior vice president of Vertex International, said in a statement that the company is “delighted” to have reached a deal with the National Health Service (NHS), adding that the reimbursement agreement will ensure “long-term access” to Kaftrio, Symkevi and Orkambi for cystic fibrosis (CF) patients in England. Vertex is currently in talks with NHS England as well as the drug pricing watchdog National Institute for Health and Care Excellence (NICE) to ensure rapid access to the biotech’s next-generation triple combination CF treatment. In a Phase III readout posted in February 2024, the investigational therapy, dubbed vanza triple, matched Kaftrio in terms of improving patients’ lung function, and outperformed the approved treatment in terms of sweat chloride levels. Thursday’s reimbursement deal comes after the NICE in October 2023 declined to recommend Kaftrio, Symkevi and Orkambi for use in CF patients. At the time, the watchdog said that while the drugs’ efficacy data support their clinical benefit, they were too expensive to be covered. “The most likely cost-effectiveness estimates for [Kaftrio, Orkambi and Symkevi] are above the range that NICE considers an acceptable use of NHS resources,” the agency wrote. However, earlier this week, NICE reversed its recommendation. In its final draft guidance, the watchdog said that given the severity of CF and its effects of quality and length of life, the cost-effectiveness estimates for Kaftrio, Symkevi and Orkambi now fell within its threshold of acceptable use of NHS resources. While NICE’s recommendation and the NHS deal names three of Vertex’s CF drugs, the centerpiece is Kaftrio, which the watchdog said yielded better short- and long-term improvements than Symkevi and Orkambi. Kaftrio is also known as Trikafta in the U.S. and is a three-drug combo that first won the FDA’s approval in October 2019, allowing its use in patients aged 12 years and older bearing at least one copy of the F508del mutation in the CTFR gene. Trikafta works by increasing the number and improving the function of F508del-CFTR proteins at the cell surface. Trikafta won additional approvals in 2021, for use in CF patients ages 6 to 11 years, and in 2023, for patients 2 through 5 years. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Phase 3Drug Approval

18 Jun 2024

·www.biospace.com

Enlaza Therapeutics Appoints Jeffrey Leiden, M.D., Ph.D., as a Key Advisor

Executive Chairperson and former CEO of Vertex Pharmaceuticals to help guide the development of a high-value pipeline of first-in-class covalent protein drugs from Enlaza’s War-Lock™ platform LA JOLLA, Calif.--(BUSINESS WIRE)-- Enlaza Therapeutics, the first covalent biologic platform company, today announced the appointment of Dr. Jeffrey Leiden, Executive Chairperson of Vertex Pharmaceuticals, as a key advisor to the company. Dr. Leiden has more than 40 years of experience in the biopharma industry developing life-improving medicines and building companies that transform the industry. “Jeff is one of the most accomplished and admired leaders in our industry. He has dedicated his career to developing important first-in-class medicines from novel breakthrough technologies that have helped millions of people with serious diseases,” said Sergio Duron, Ph.D., CEO of Enlaza Therapeutics. “With our War-Lock platform, we can create covalent protein drugs with the potential to improve treatments for many diseases. Jeff’s guidance will be invaluable as we establish a diverse pipeline and advance our lead assets toward clinical development.” "While covalency has been a long-standing strategy in small molecule drug development, Enlaza is the first to incorporate covalency into biologics, unlocking a new class of protein therapeutics," said Dr. Leiden. "I look forward to working closely with the Enlaza team to realize the full potential of this exciting new drug discovery and development platform and help create meaningful new medicines for patients.” As CEO and President of Vertex from 2012 through 2020, Dr. Leiden built a robust pipeline of drug candidates, with a particular focus on therapies that cure or modify the course of disease. Under his leadership, Vertex delivered the first and only medicines to treat the underlying cause of cystic fibrosis for patients with certain forms of the disease, including KALYDECO®, ORKAMBI®, SYMDEKO® and TRIKAFTA®. In 2015, he established a collaboration with CRISPR Therapeutics to develop transformative therapies for sickle cell disease (SCD), beta thalassemia (TDT) and other diseases; and in 2023, CASGEVY™ was approved as the first gene-editing therapy in the world for SCD and TDT. In 2019, he led the Vertex acquisition of Semma Therapeutics to develop a clinical program to investigate what may be the first potentially curative stem cell-based therapy for type 1 diabetes. Prior to joining Vertex, Dr. Leiden was a managing director at Clarus Ventures, a life sciences venture capital firm, from 2006 through 2012. Dr. Leiden was President, Chief Operating Officer and Chief Scientific Officer of Abbott Laboratories, Pharmaceuticals Products Group, and a member of the board of directors of Abbott Laboratories from 2000 to 2006. At Abbott he led the development and commercialization of HUMIRA®. From 1987 to 2000, Dr. Leiden held several academic appointments, including the Rawson Professor of Medicine and Pathology and Chief of Cardiology and Director of the Cardiovascular Research Institute at the University of Chicago, the Elkan R. Blout Professor of Biological Sciences at the Harvard School of Public Health, and Professor of Medicine at Harvard Medical School. He is an elected member of both the American Academy of Arts and Sciences and the National Academy of Medicine. About the War-Lock™ Platform Enlaza’s covalent biologic platform, called War-Lock, creates highly specific therapeutic warheads that covalently bind to drug targets of interest. This white-space technology enables, for the first time, a covalent-acting protein drug that retains the selectivity of small-format biologics. Protein drugs produced by the platform can be modified to incorporate various payloads and achieve specific delivery to target tissues with high fidelity. About Enlaza Therapeutics Enlaza Therapeutics is pioneering the field of covalent biologics. This novel class of protein therapeutics has the potential to delivers more efficacious and safer treatments for patients. The company's proprietary War-Lock™ platform leverages leading synthetic biology technology for site-specific covalent coupling driven by drug binding. Enlaza is building a pipeline of first-in-class covalent biologics. For more information, please visit .

Executive Change

100 Deals associated with Ivacaftor

External Link

KEGG	Wiki	ATC	Drug Bank
D09916	Ivacaftor	R07AX02	DB08820

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Cystic Fibrosis	US	Vertex Pharmaceuticals, Inc.	31 Jan 2012

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cough	Phase 3	AU	Vertex Pharmaceuticals, Inc.	12 Oct 2021
Cough	Phase 3	BE	Vertex Pharmaceuticals, Inc.	12 Oct 2021
Cough	Phase 3	CA	Vertex Pharmaceuticals, Inc.	12 Oct 2021
Cough	Phase 3	ES	Vertex Pharmaceuticals, Inc.	12 Oct 2021
Glucose Metabolism Disorders	Phase 3	AU	Vertex Pharmaceuticals, Inc.	15 Jan 2021
Glucose Metabolism Disorders	Phase 3	BE	Vertex Pharmaceuticals, Inc.	15 Jan 2021
Glucose Metabolism Disorders	Phase 3	CZ	Vertex Pharmaceuticals, Inc.	15 Jan 2021
Glucose Metabolism Disorders	Phase 3	FR	Vertex Pharmaceuticals, Inc.	15 Jan 2021
Glucose Metabolism Disorders	Phase 3	IT	Vertex Pharmaceuticals, Inc.	15 Jan 2021
Glucose Metabolism Disorders	Phase 3	NL	Vertex Pharmaceuticals, Inc.	15 Jan 2021

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Biospace Manual	Not Applicable	Cystic Fibrosis	18	Dispersome	lzfiokjkzk(xcaiknnhjp) = equivalent weppivojra (ocymgnnbzi ) View more	Superior	13 May 2024
Biospace Manual	Not Applicable	Cystic Fibrosis	18	Kalydeco		Superior	13 May 2024
NCT04545515 (CTgov)	Phase 3	Cystic Fibrosis	120	IVA+ELX/TEZ/IVA	cbnptcrqgw(abilupmtff) = dclrtzedfw iushxjrvhm (swvteqgfgl, hhzkoygovw - lzobqzpnyl) View more	-	08 May 2024
NCT04058366 (CTgov)	Phase 3	Cystic Fibrosis	251	IVA+ELX/TEZ/IVA	quhlycbyzi(zioxvwlitf) = ovtmngrqho tlhyrzsufz (ptpydbkurh, xbnzcxwadj - ovpxxnppbg) View more	-	16 Jan 2024
NCT03085485 (CTgov)	Phase 2	Bronchitis, Chronic	40	Ivacaftor 150 MG (Ivacaftor)	inhrjpnxfk(ptmqshzbsy) = nvevlttxbj ahyysgmepk (mkrztzlrzo, gieobljcuz - szxlhyfaog) View more	-	21 Dec 2023
NCT03085485 (CTgov)	Phase 2	Bronchitis, Chronic	40	Placebo (Placebo)	inhrjpnxfk(ptmqshzbsy) = cndkwiochv ahyysgmepk (mkrztzlrzo, hstdkvjxve - qstfplkdyk) View more	-	21 Dec 2023
AASLD2023	Not Applicable	Cystic Fibrosis	154	Elexacaftor/tezacaftor/ivacaftor	nxupyhvmip(gyrjguiswv) = aqnobbtsau xwjsxvydtb (kfwoshmtyt ) View more	-	10 Nov 2023
NCT04969224 (CTgov)	Phase 3	Cough \| Cystic Fibrosis	82	IVA+ELX/TEZ/IVA	nqkihbpdei(uvrzsszizm) = ptfoooorou vygyoasqib (pstfsliohr, qsqgdttwuu - vbpsnotydt) View more	-	03 Oct 2023
NCT04599465 (CTgov)	Phase 3	Cystic Fibrosis \| Glucose Metabolism Disorders	69	IVA+ELX/TEZ/IVA	kdrblckwph(iywvbihrol) = awwmiweilp crfxwfpybd (dgkqplmtne, ivowxhyzlu - wuiavfmmct) View more	-	03 Aug 2023
NCT05111145 (CTgov)	Phase 3	Cystic Fibrosis	86	IVA+ELX/TEZ/IVA	npiarmjgem(ovlmgwnmue) = fsicqargud inheeekhlw (nfkhoisehy, crnifkgkqt - wdqcsnphds) View more	-	11 Jul 2023
NCT04043806 (CTgov)	Phase 3	Cystic Fibrosis	458	IVA+ELX/TEZ/IVA	rrksshtopu(osdhqcnjio) = lzmiinhihi obwkrbpfkf (izvcxledpp, elnjbkmsts - vrmcxtobke) View more	-	06 Jul 2023

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