- Biogen and AbbVie Announce the Voluntary Worldwide Withdrawal of Marketing Authorizations for ZINBRYTA® (daclizumab) for Relapsing Multiple Sclerosis
- ZINBRYTA (daclizumab) voluntarily withdrawn from market worldwide
- Zinbryta (daclizumab) for the Treatment of Multiple Sclerosis
- Causes of multiple sclerosis
- Zinbryta (daclizumab)’s mechanism of action
- Clinical trials
- Zinbryta (Daclizumab) for Multiple Sclerosis
- How Zinbryta works
- History of Zinbryta
- Next steps for Zinbryta
- Other Zinbryta info
Biogen and AbbVie Announce the Voluntary Worldwide Withdrawal of Marketing Authorizations for ZINBRYTA® (daclizumab) for Relapsing Multiple Sclerosis
CAMBRIDGE, Mass. & NORTH CHICAGO, Ill.–(BUSINESS WIRE)–Biogen (Nasdaq:BIIB) and AbbVie (NYSE:ABBV) today announced the voluntary worldwide withdrawal of ZINBRYTA for relapsing multiple sclerosis.
The companies believe that characterizing the complex and evolving benefit/risk profile of ZINBRYTA will not be possible going forward given the limited number of patients being treated.
“Biogen believes the voluntary worldwide withdrawal of ZINBRYTA, a treatment for relapsing multiple sclerosis, is in the best interest of patients,” said Alfred Sandrock, M.D., Ph.D.
, executive vice president and chief medical officer at Biogen. “Biogen and AbbVie continue to prioritize patient safety and the care of multiple sclerosis patients worldwide.”
Biogen will continue to work collaboratively with regulatory authorities in the withdrawal of product and with healthcare providers worldwide in their support of ZINBRYTA patients.
Patients currently treated with ZINBRYTA should contact their healthcare provider if they have any questions or concerns.
ZINBRYTA (daclizumab) is currently available in the EU, U.S., Switzerland, Canada and Australia. ZINBRYTA is a prescription medicine used to treat adults with relapsing forms of multiple sclerosis (MS).
Because of its risks, ZINBRYTA is generally used in people who have tried two or more MS medicines that have not worked well enough.
It is not known if ZINBRYTA is safe and effective for use in children under 18 years of age.
At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases.
Founded in 1978 as one of the world’s first global biotechnology companies by Charles Weissman, Heinz Schaller, Kenneth Murray and Nobel Prize winners Walter Gilbert and Phillip Sharp, today Biogen has the leading portfolio of medicines to treat multiple sclerosis; has introduced the first and only approved treatment for spinal muscular atrophy; and is focused on advancing neuroscience research programs in Alzheimer’s disease and dementia, multiple sclerosis and neuroimmunology, movement disorders, neuromuscular disorders, pain, ophthalmology, neuropsychiatry, and acute neurology. Biogen also manufactures and commercializes biosimilars of advanced biologics. We routinely post information that may be important to investors on our website at www.biogen.com. To learn more, please visit www.biogen.com and follow us on social media – , LinkedIn, , .
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ZINBRYTA (daclizumab) voluntarily withdrawn from market worldwide
On Friday March 2, 2018, Biogen Canada and AbbVie announced the voluntary withdrawal of ZINBRYTA® (daclizumab) from the market worldwide due to safety concerns. Eight reports of brain inflammation (encephalitis and meningoencephalitis) were reported in Europe in individuals being treated with daclizumab.
According to Biogen, given the nature and complexity of adverse events being reported, further assessment of the benefit/risk profile of ZINBRYTA® will not be possible going forward given the limited number of patients being treated.
Biogen is working closely with regulatory authorities, such as Health Canada, and healthcare providers to support people treated with ZINBRYTA®.
Patients should contact their healthcare team to discuss their treatment plan; and must not stop taking their medication until they have had a discussion with their physician. ZINBRYTA® was a second-line, once monthly self-administered monoclonal antibody for RRMS.
Health Canada has recently approved Biogen and AbbieVie’s newest disease modifying therapy, Zinbryta™ (daclizumab). Zinbryta is a humanized monoclonal antibody that binds to CD25, an interleukin-2 (IL-2) receptor subunit on the surface of T-cells.
CD25 can be found at high levels on T-cells that become activated in people with MS. The antibody prevents activation and growth of disease-causing immune cells.
Zinbryta also appears to increase the activity of certain beneficial immune cells called CD56(bright) natural killer cells which can regulate the immune system by destroying disease-causing T cells.
Zinbryta is the first monoclonal antibody to be available for self-administration once-monthly through subcutaneous injection (under the skin). Zinbryta is indicated for adults with active relapsing remitting multiple sclerosis (RRMS), who have had an inadequate response to, or are unable to tolerate, one or more therapies indicated for the treatment of relapsing forms of MS.
The most common adverse effects reported include fatigue, headache, nausea, rash, musculoskeletal disorders, allergic reactions, infections, elevated liver enzymes, heart problems, and reduced platelet number.
The Health Canada approval of Zinbryta is results from two clinical trials:
- DECIDE, a phase III trial with more than 1,800 participants from 28 countries, focused on comparing a once monthly subcutaneous injection of daclizumab to a once weekly intramuscular injection of interferon beta-1a in participants with RRMS over 144 weeks. Participants administered daclizumab showed a 45% reduction in annualized relapse rate compared to participants administered interferon beta-1a. Additional results revealed a 54% reduction in the number of new or enlarging brain lesions relative to interferon beta-1a at 96 weeks.
- The Phase IIb SELECT trial examined the effects of 150mg or 300mg daclizumab treatment compared to a dummy drug (placebo) over 52 weeks in over 600 participants. Participants treated with daclizumab had lower relapse rates compared to placebo treated participants (150mg showed a 54% reduction; 300mg showed a 50% reduction), and more relapse free patients compared to the control group (150mg 81%; 300mg 80%).
The approval of Zinbryta provides another second line option for people with active RRMS who have had an inadequate response to, or are unable to tolerate, one or more therapies indicated for the treatment of MS. Selecting an MS therapy should be done in consultation with a health care team. The MS Society of Canada will provide updates on availability and public coverage of Zinbryta™ as they become available.
Full drug information will be available on the MS Society website shortly.
Zinbryta (daclizumab) for the Treatment of Multiple Sclerosis
Zinbryta (daclizumab) is an injectable formulation jointly developed by Biogen and Abbive for the treatment of relapsing forms of multiple sclerosis (MS) in adults.
The biological license application (BLA) for Zinbryta (daclizumab) was submitted to the US Food and Drug Administration (FDA) in February 2015. The FDA approved Zinbryta (daclizumab) as a once-a-month, self-administered, subcutaneous treatment for MS in adults, in May 2016.
The Committee for Medical Products for Human Use (CHMP) of the European Medical Agency (EMA) recommended a positive opinion to grant marketing authorisation (MA) for Zinbryta (daclizumab) in April 2016. The European Commission (EC) granted marketing authorisation for Zinbryta in July 2016.
The drug was approved in Australia and Canada in September and December 2016, respectively. It was also received approved in Switzerland in February 2017.
Causes of multiple sclerosis
MS is a chronic neurological disorder caused by damage of the myelin sheath that surrounds and protects the nerve cells. It usually attacks the central nervous system (CNS), which includes the brain, spinal cord and optic nerves.
Damage to the myelin sheath causes messages between brain and body to be slowed down or blocked, resulting in a number of symptoms such as visual disturbance, muscle weakness, trouble with co-ordination, numbness and memory problems.
MS is usually termed as an autoimmune disease, where the body’s immune system attacks the healthy cells accidentally. It is more commonly seen in women aged between 20 and 40 years.
There is no permanent cure for the disease, but medicines may control the symptoms and slow it down considerably.
Zinbryta (daclizumab)’s mechanism of action
The exact mechanism of action of Zinbryta is unknown. It is a new form of a humanised monoclonal antibody that binds to CD25, a high-affinity interleukin-2 (IL-2) receptor subunit on T-cells that become activated in people suffering from MS.
Zinbryta modulates the interleukin-2 (IL-2) signalling without causing any immune cell depletion. It should be referred to patients with relapsing MS (RMS) that have had an inadequate response to two or more therapies.
The US FDA and EC approved Zinbryta (daclizumab) results obtained from clinical trials DECIDE and SELECT, which were conducted on more than 2,400 patients with relapsing forms of RMS.
SELECT is a multi-centre, randomised, double-blinded, Phase IIb study conducted in more than 417 patients with RMS to evaluate the safety and efficacy of Zinbryta 150mg and 300mg against placebo. The drug was administered to the patients subcutaneously every four weeks for one year.
DECIDE is a Phase III, global, randomised, double-blinded, multi-centre study conducted in 1,841 patients suffering from RMS.
The study included two arms. One was given 150mg of subcutaneous Zinbryta every four weeks and the other was given AVONEX (interferon beta-1a) 30mcg IM once a week.
“Zinbryta is approved in Switzerland, Canada and Australia.”
The trial achieved its primary endpoint of significant reduction in annualised relapse rate (ARR) and first secondary end point of reduction in the number of newly enlarging T2 hyper-intense lesions.
However, the study did not demonstrate a statistical significance in its secondary end point of evaluating proportion of patients with sustained disability progression, measured by Expanded Disability Status Scale (EDSS) after 12 weeks.
The commonly observed adverse reactions in patients treated with Zinbryta were nasopharyngitis, upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal pain, bronchitis, eczema, lymphadenopathy, depression and increased alanine aminotransferase (ALT).
Zinbryta (Daclizumab) for Multiple Sclerosis
Zinbryta (daclizumab), a humanized monoclonal antibody produced by Biogen and AbbVie, is an approved treatment for relapsing multiple sclerosis (RMS) in the U.S. and in Europe.
How Zinbryta works
Zinbryta is a formulation of a monoclonal antibody against the CD25 subunit of interleukin 2 (IL-2) receptors. These receptors are highly expressed on reactive T-cells in MS patients.
By selectively targeting the T-cells with CD25, Zinbryta prevents the expansion of CD25-positive, autoreactive T-cells. It further promotes the activity of CD 65-positive natural killer cells, which clean up the already activated CD25-positive T-cells.
Therefore, Zinbryta both stops and prevents inflammation caused by CD25-positive T-cells.
In the high-yield formulation, Zinbryta is intended to be administered subcutaneously (beneath the skin) once every four weeks. At this dose, Zinbryta binds to all CD25 receptors within 10 hours and remains bound for 64 days.
History of Zinbryta
Daclizumab was originally pursued for the treatment of acute organ rejection in patients with kidney transplants by Roche under the trade name Zenapax. The medication was available in the U.S. and European Union, but it was withdrawn for commercial reasons.
Daclizumab is now called Zinbryta for use in RMS patients. Two clinical trials, DECIDE (NCT01064401) and SELECT (NCT00390221), formed the basis of the biological licence application (BLA) submission to the U.S. Food and Drug Administration (FDA) by Biogen and AbbVie.
The SELECT study compared the effect of different doses of daclizumab (300 mg and 150 mg) to placebo over a one-year period in participants with RMS and showed that the lower dose of daclizumab (150 mg) reduced the relapse rate by 54% compared to placebo.
DECIDE, a Phase 3 study involving 1,841 participants with RMS, showed that Zinbryta reduced the rate of relapses by 45% and also decreased the activity of the disease, as observed in MRI scans, over 144 weeks compared to Avonex, another drug approved for the treatment of RMS.
Next steps for Zinbryta
The FDA accepted Biogen and Abbvie’s BLA for Zinbryta for RMS, and Zimbryta was officially approved by the FDA on May 27, 2016.
The European Medicines Agency (EMA) also validated the Marketing Authorization Application for Zinbryta for the treatment of RMS, and a review process by EMA’s Committee for Medicinal Products for Human Use (CHMP) began in March 2015. About a year later, in April 2016, CHMP adopted a positive opinion, recommending marketing authorization in Europe for Zinbryta to treat RMS.
The EMA eventually approved Zinbryta for the treatment of adult patients with RMS in July 2016.
The decision was followed by the National Health Service (NHS) in England and Wales in March 2017 and by the Scottish Medicines Consortium (SMC) on April 10, 2017.
In England and Wales, Zinbryta is indicated for the treatment of RMS in patients who have relapses while taking one of the other available disease modifying drugs, and for the treatment of rapidly evolving RMS when there were two or more relapses in the previous year as measured with magnetic resonance imaging (MRI).
In Scotland, Zinbryta can be prescribed for rapidly evolving severe RMS, or RMS with inadequate response to disease modifying therapy.
The benefits of Zinbryta in patients with secondary progressive MS (SPMS) have also been investigated, by PDL BioPharma, in 2008. Eight percent of the patients enrolled in a Phase 2 clinical trial (NCT00109161) had SPMS (the other 92% had RMS).
Other Zinbryta info
Zinbryta has a black box warning about the potential for severe liver injury, including life-threatening and fatal events. Therefore it is highly recommended that liver function is monitored before starting and during treatment with Zinbryta. Common side effects include skin rash and elevated liver enzymes.
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