CLINICAL TRIALS PROFILE FOR ZINBRYTA

All Clinical Trials for ZINBRYTA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00246129 ↗	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation	Completed	EMagnusson	Phase 4	2005-10-01	The advent of new, potent immunosuppressive (anti-rejection) drugs over the past ten years has substantially reduced the risk of rejection after kidney transplantation, has allowed the development of immuno-suppressive regimens that do not use long-term steroids (steroid avoidance), and has improved transplant success rates both in the short and medium term. The main new agents used in these modern regimens are the calcineurin inhibitor (CNI) tacrolimus; the anti-proliferative agent mycophenolate; and induction agents which are used to provide effective early suppression of the rejection process; these include monoclonal antibodies (MoAb) such as IL-2 receptor blocking antibodies (IL-2R MoAb: basiliximab and daclizumab) and the anti-CD52 antibody Campath-1H (alemtuzumab). Although almost all modern immunosuppressive regimens involve one or more of these agents, it is not known which is the safest and most effective combination. This randomised controlled trial compares two steroid sparing regimens which have been used with very good short and medium term results at St Mary's Hospital Renal and Transplant Unit over the last 5 years. The primary hypothesis is that the alemtuzumab/tacrolimus regimen is as effective and safe as the IL-2R MoAb/tacrolimus/mycophenolate regimen.
NCT00246129 ↗	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation	Completed	Hammersmith Hospitals NHS Trust	Phase 4	2005-10-01	The advent of new, potent immunosuppressive (anti-rejection) drugs over the past ten years has substantially reduced the risk of rejection after kidney transplantation, has allowed the development of immuno-suppressive regimens that do not use long-term steroids (steroid avoidance), and has improved transplant success rates both in the short and medium term. The main new agents used in these modern regimens are the calcineurin inhibitor (CNI) tacrolimus; the anti-proliferative agent mycophenolate; and induction agents which are used to provide effective early suppression of the rejection process; these include monoclonal antibodies (MoAb) such as IL-2 receptor blocking antibodies (IL-2R MoAb: basiliximab and daclizumab) and the anti-CD52 antibody Campath-1H (alemtuzumab). Although almost all modern immunosuppressive regimens involve one or more of these agents, it is not known which is the safest and most effective combination. This randomised controlled trial compares two steroid sparing regimens which have been used with very good short and medium term results at St Mary's Hospital Renal and Transplant Unit over the last 5 years. The primary hypothesis is that the alemtuzumab/tacrolimus regimen is as effective and safe as the IL-2R MoAb/tacrolimus/mycophenolate regimen.
NCT02881567 ↗	Efficacy and Safety of Daclizumab in Participants With RRMS Switching From Natalizumab	Terminated	AbbVie	Phase 3	2017-04-18	The primary objective of the study is to evaluate the effects of treatment with daclizumab on the proportion of participants relapse-free at 6 months in Relapsing-Remitting Multiple Sclerosis (RRMS) participants, who switched from treatment with natalizumab to daclizumab due to safety concerns. The secondary objectives of this study in this study population are to evaluate the effects of daclizumab on the following: 1) Multiple Sclerosis (MS) relapse activity including the annualized relapse rate (ARR) and the proportion of participants experiencing relapses requiring hospitalization and/or steroid treatment; 2) MS-related outcomes measured using magnetic resonance imaging (MRI); 3) Safety and tolerability in participants previously treated with natalizumab.
NCT02881567 ↗	Efficacy and Safety of Daclizumab in Participants With RRMS Switching From Natalizumab	Terminated	Biogen	Phase 3	2017-04-18	The primary objective of the study is to evaluate the effects of treatment with daclizumab on the proportion of participants relapse-free at 6 months in Relapsing-Remitting Multiple Sclerosis (RRMS) participants, who switched from treatment with natalizumab to daclizumab due to safety concerns. The secondary objectives of this study in this study population are to evaluate the effects of daclizumab on the following: 1) Multiple Sclerosis (MS) relapse activity including the annualized relapse rate (ARR) and the proportion of participants experiencing relapses requiring hospitalization and/or steroid treatment; 2) MS-related outcomes measured using magnetic resonance imaging (MRI); 3) Safety and tolerability in participants previously treated with natalizumab.

Clinical Trial Conditions for ZINBRYTA

Condition Name

Condition Name for ZINBRYTA
Intervention	Trials
Kidney Diseases	1
Kidney Failure	1
Kidney Transplantation	1
Relapsing-Remitting Multiple Sclerosis (RRMS)	1

Condition MeSH

Condition MeSH for ZINBRYTA
Intervention	Trials
Multiple Sclerosis, Relapsing-Remitting	1
Multiple Sclerosis	1
Renal Insufficiency	1
Kidney Diseases	1

Clinical Trial Locations for ZINBRYTA

Trials by Country

Trials by Country for ZINBRYTA
Location	Trials
Germany	4
United States	3
Italy	2
United Kingdom	1
Puerto Rico	1

Trials by US State

Trials by US State for ZINBRYTA
Location	Trials
Iowa	1
Florida	1
Wisconsin	1

Clinical Trial Progress for ZINBRYTA

Clinical Trial Phase

Clinical Trial Phase for ZINBRYTA
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	1

Clinical Trial Status

Clinical Trial Status for ZINBRYTA
Clinical Trial Phase	Trials
Completed	1
Terminated	1

Clinical Trial Sponsors for ZINBRYTA

Sponsor Name

Sponsor Name for ZINBRYTA
Sponsor	Trials
EMagnusson	1
Hammersmith Hospitals NHS Trust	1
AbbVie	1

Sponsor Type

Sponsor Type for ZINBRYTA
Sponsor	Trials
Other	2
Industry	2

ZINBRYTA (Daclizumab): A Comprehensive Update on Clinical Trials, Market Analysis, and Projections

Introduction to ZINBRYTA

ZINBRYTA (daclizumab) is a humanized monoclonal antibody developed jointly by Biogen and AbbVie for the treatment of relapsing forms of multiple sclerosis (MS). It was approved by the U.S. Food and Drug Administration (FDA) in May 2016 as a once-monthly, self-administered, subcutaneous treatment[3].

Mechanism of Action

ZINBRYTA works by selectively binding to the high-affinity interleukin-2 (IL-2) receptor subunit (CD25) on T-cells that become activated in people with MS. This binding modulates IL-2 signaling without causing general immune cell depletion. It decreases abnormally-activated T-cells and pro-inflammatory lymphoid tissue inducer cells, while increasing CD56 bright natural killer (NK) cells, which help regulate the immune system[2][3].

Clinical Trials Overview

The FDA approval of ZINBRYTA was primarily based on results from two clinical trials: the Phase 2b SELECT and the Phase 3 DECIDE studies. These global, randomized, double-blind, controlled studies involved approximately 2,400 people living with relapsing-remitting MS (RMS)[1][3].

DECIDE Study

The DECIDE study was the largest and longest head-to-head Phase 3 clinical trial ever conducted in MS. It compared ZINBRYTA to AVONEX (interferon beta-1a) intramuscular injection. Key findings included:

• Relapse Reduction: ZINBRYTA significantly reduced the annualized relapse rate (ARR) by 45% compared to AVONEX up to 144 weeks[1][3].
• MRI Lesions: ZINBRYTA reduced the mean number of new or newly enlarging T2-hyperintense lesions by 54% compared to AVONEX at 96 weeks[3].
• Relapse-Free Patients: At up to 144 weeks, 67% of patients on ZINBRYTA were relapse-free compared to 51% of patients on AVONEX[3].

SELECT Study

The SELECT study was a Phase 2b trial that also demonstrated ZINBRYTA's efficacy. It showed a 54% reduction in ARR compared to placebo at 52 weeks[1][3].

EXTEND Study

The EXTEND study is an ongoing, Phase 3, open-label extension of the DECIDE study. Interim results presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) showed sustained efficacy of ZINBRYTA for up to five years. The study reinforced ZINBRYTA’s long-term benefits in maintaining relapse-free status and preventing disability progression[4].

Efficacy and Safety Profile

No Evidence of Disease Activity (NEDA)

A post-hoc analysis from the DECIDE study showed that significantly more patients treated with ZINBRYTA achieved NEDA status compared to those on AVONEX. This was particularly evident during the 24-96 week period, with 44.7% of ZINBRYTA patients achieving NEDA status versus 22.4% of AVONEX patients[4].

Safety Profile

ZINBRYTA's safety profile includes a boxed warning for the risk of hepatic injury, including autoimmune hepatitis, and other immune-mediated disorders. The drug is restricted to prescribers, pharmacies, and patients enrolled in the ZINBRYTA Risk Evaluation and Mitigation Strategy (REMS) Program, which includes required monthly liver function tests[3].

Common adverse reactions include nasopharyngitis, upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal pain, bronchitis, eczema, lymphadenopathy, depression, and increased alanine aminotransferase (ALT)[5].

Market Analysis

Regulatory Approvals

ZINBRYTA received FDA approval in May 2016 and was granted marketing authorization by the European Commission in July 2016. It was also approved in Australia, Canada, and Switzerland in subsequent months[5].

Market Impact

ZINBRYTA offers a unique once-monthly dosing regimen, which is a significant advantage in the MS treatment market. Its superior efficacy in reducing relapses and MRI lesions compared to traditional therapies like AVONEX makes it an attractive option for patients and healthcare providers[1][3].

However, the drug's use is generally reserved for patients who have had an inadequate response to two or more therapies indicated for MS, which may limit its market penetration compared to first-line treatments[3].

Market Projections

Patient Population

The global MS market is growing due to an increasing patient population and the need for more effective treatments. ZINBRYTA, with its novel mechanism of action and demonstrated efficacy, is poised to capture a significant share of this market, particularly among patients who have not responded well to other therapies.

Competitive Landscape

The MS treatment market is highly competitive, with several disease-modifying therapies available. However, ZINBRYTA's unique dosing schedule and its ability to modulate the immune system without causing general immune cell depletion set it apart from other treatments. This differentiation could help it maintain a strong market position despite competition[2][3].

Future Outlook

Despite its promising clinical trial results and unique benefits, ZINBRYTA faces challenges related to its safety profile and the need for strict monitoring. However, ongoing studies like the EXTEND trial continue to reinforce its long-term efficacy and safety, which could further solidify its place in the MS treatment landscape.

"ZINBRYTA is a new, once-monthly, self-administered, subcutaneous treatment option for people living with relapsing forms of MS, including those whose disease activity has been insufficiently controlled by their prior therapy," said Ralph Kern, M.D., senior vice president, Worldwide Medical, Biogen[4].

Key Takeaways

• Clinical Efficacy: ZINBRYTA demonstrated superior efficacy in reducing relapses and MRI lesions compared to AVONEX in clinical trials.
• Unique Mechanism: It modulates IL-2 signaling without causing general immune cell depletion.
• Safety Profile: Includes a boxed warning for hepatic injury and other immune-mediated disorders, requiring strict monitoring.
• Market Position: Offers a unique once-monthly dosing regimen, appealing to patients and healthcare providers.
• Future Outlook: Ongoing studies continue to support its long-term efficacy and safety, solidifying its place in the MS treatment market.

FAQs

Q: What is ZINBRYTA used for?

A: ZINBRYTA is used for the treatment of relapsing forms of multiple sclerosis (MS) in adults.

Q: How is ZINBRYTA administered?

A: ZINBRYTA is administered subcutaneously once a month.

Q: What are the key clinical trial findings for ZINBRYTA?

A: ZINBRYTA significantly reduced the annualized relapse rate and the number of new or newly enlarging T2-hyperintense lesions compared to AVONEX in clinical trials.

Q: What are the common adverse reactions associated with ZINBRYTA?

A: Common adverse reactions include nasopharyngitis, upper respiratory tract infection, rash, influenza, and others.

Q: Why is ZINBRYTA restricted to certain patients and healthcare providers?

A: Due to its safety profile, ZINBRYTA is restricted to patients and healthcare providers enrolled in the ZINBRYTA Risk Evaluation and Mitigation Strategy (REMS) Program.

Sources

1. Biogen and AbbVie Receive FDA Approval of Once-Monthly ZINBRYTA (daclizumab) for Multiple Sclerosis. AbbVie News. May 27, 2016.
2. EMA validates marketing authorization application for ZINBRYTA for treatment of multiple sclerosis. Biogen Press Release. March 27, 2015.
3. Biogen and AbbVie Receive FDA Approval of Once-Monthly ZINBRYTA (daclizumab) for Multiple Sclerosis. PR Newswire. May 27, 2016.
4. New Data Presented at ECTRIMS Reinforce Efficacy of ZINBRYTA (daclizumab) and Support Long-Term Safety Profile. Biogen Press Release.
5. Zinbryta (daclizumab) for the Treatment of Multiple Sclerosis. Clinical Trials Arena. March 22, 2018.