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每月只一次注射的多发性硬化症药物Zinbryta获欧盟批准上市
If a patient develops clinical signs or symptoms suggestive of hepatic dysfunction (e.g. unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine), it is recommended to promptly measure serum transaminases and interrupt or discontinue treatment with Zinbryta, as appropriate. In patients with prolonged elevations of serum transaminases, it is appropriate to evaluate for other possible causes, such as infection, and referral to a specialist may be required. Autoimmune hepatitis (without the presence of auto-antibodies) has been observed in clinical studies. Treatment with systemic corticosteroids may be appropriate. Refer to section below, 'Educational Guidance', for details of the Physician Guidelines and Patient Card that are recommended for use with this medicine. Educational guidance All physicians who intend to prescribe Zinbryta must ensure they are familiar with the Physician Guidelines for this medicinal product. The physician should discuss the risk of hepatic injury with patients and provide them with a Patient Card. The Card informs patients of the risk of severe hepatic injury, and its possible symptoms, so that they are aware of situations in which they should contact a healthcare professional in a timely manner. In addition, the Card explains the need for monitoring of liver function and educates the patient on the importance of adherence to their monthly blood tests. Skin reactions Skin reactions, some serious (e.g. exfoliative rash or dermatitis, toxic skin eruption), have been reported with Zinbryta. Skin reactions generally resolved with standard care, including treatment with topical or systemic steroids. If a patient develops a diffuse or highly inflammatory rash, referral to a dermatologist and discontinuation of Zinbryta may be required (see section 4.8). Depression Zinbryta should be administered with caution to patients with previous or current depressive disorders. Patients treated with Zinbryta should be advised to report any symptoms of new or worsening depression, and/or suicidal ideation to the prescribing physician. If a patient develops severe depression, and/or suicidal ideation, discontinuation of Zinbryta should be considered (see section 4.8). Infections Infections, some serious (e.g. pneumonia and bronchitis), have been reported with Zinbryta. If serious infection develops, it could be necessary to withhold treatment with Zinbryta until the infection resolves. Tuberculosis infections have been reported in patients treated with Zinbryta. In patients who have had tuberculosis or who live in endemic areas of the disease, screening for active tuberculosis should be performed before starting treatment, and patients should be monitored during treatment. In patients with severe active infection, a delay in initiation of Zinbryta therapy should be considered (see section 4.8). Zinbryta has not been studied in patients with immunodeficiency syndromes. Gastrointestinal disorders Colitis has been reported with Zinbryta. The colitis improved with discontinuation of Zinbryta and standard treatment. Referring patients who develop symptoms of colitis (e.g. abdominal pain, fever, prolonged diarrhoea) to a specialist is advisable (see section 4.8). Lymphopenia When observed during Zinbryta clinical studies, lymphopenia was mostly mild to moderate (≥ 500/mm3). Sustained severe lymphopenia (< 500/mm3), was not observed in clinical studies with Zinbryta. However, as a precaution, monitoring of complete blood count is recommended every 3 months. The risk of Progressive Multifocal Leukoencephalopathy (PML) associated to the treatment with Zinbryta has not been established. Excipient related considerations This medicinal product contains 0.14 mmol sodium per dose. It is essentially 'sodium-free' and can be used by patients on a sodium-restricted diet. 4.5 Interaction with other medicinal products and other forms of interaction Zinbryta is not expected to undergo metabolism by hepatic enzymes or renal elimination. Drug interactions between Zinbryta and symptomatic MS therapy (e.g. antispastic agents, fampridine) are not expected; however there is limited data on concomitant use of Zinbryta with MS symptomatic therapies. Immunisations The safety of immunisation with live viral vaccines during treatment with Zinbryta has not been studied. Vaccination with live vaccines is not advised during treatment and up to 4 months after discontinuation. In a clinical study, patients (n=90) on long-term treatment with Zinbryta mounted appropriate immune responses to an inactivated trivalent seasonal influenza vaccine. The magnitude of the immune response to the seasonal influenza vaccine, and proportion of patients with seroconversion and seroprotection were consistent with those observed in healthy volunteer populations. Patients on Zinbryta may receive non-live vaccines. 4.6 Fertility, pregnancy and lactation Pregnancy There are limited data from the use of Zinbryta in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reprotoxicity (see section 5.3). Zinbryta should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Breast-feeding Available toxicology data in lactating cynomolgus monkeys have shown excretion of daclizumab in milk (for details see section 5.3). It is not known whether Zinbryta is secreted in human milk. Although human IgG is secreted into human milk, published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts. A risk to newborns/infants cannot be excluded. If a woman wishes to breast-feed during treatment with Zinbryta, the benefit of breast-feeding to the child and of therapy to the woman should be considered. Fertility No impact on male or female fertility as assessed by fertility indices was detected in animal studies (see section 5.3). There are no data on the effects of Zinbryta on human fertility. 4.7 Effects on ability to drive and use machines Zinbryta has no or negligible influence on the ability to drive and use machines. 4.8 Undesirable effects Summary of the safety profile In the placebo-controlled study (the SELECT study), 417 patients received Zinbryta (150 mg, n=208; 300 mg, n=209; every 4 weeks) for up to 1 year. In the active-controlled study (the DECIDE study), 919 patients received Zinbryta (150 mg, every 4 weeks) and 922 patients received interferon beta-1a intramuscular, (30 microgram weekly) for a minimum of 2 years and up to 3 years. The most commonly reported adverse reactions leading to discontinuation in patients treated with Zinbryta were hepatic reactions, including elevations of serum transaminases (5%), and cutaneous reactions (4%) (see section 4.4). The most common adverse reactions reported for Zinbryta were rash, increased alanine aminotransferase (ALT), depression, nasopharyngitis, upper respiratory tract infection, influenza, oropharyngeal pain, and lymphadenopathy. Tabulated list of adverse reactions The adverse reactions are presented as MedDRA preferred terms under the MedDRA System Order Class by frequency and incidence. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The incidence of the adverse reactions is expressed according to the following categories: • Very common (≥ 1/10) • Common (≥1/100 to <1/10) • Uncommon (≥1/1,000 to <1/100) Table 2: Adverse reactions reported for Zinbryta 150mg
†Observed with a ≥2% higher incidence than interferon beta-1a (intramuscular) Description of selected adverse reactions Hepatic injury Elevations of serum transaminases and severe hepatic injury have occurred in patients treated with Zinbryta. Serious reactions, including autoimmune hepatitis, hepatitis and jaundice, were observed in 1% of patients. In a clinical study, a case of fatal autoimmune hepatitis occurred in a patient re-initiating treatment with 300 mg of daclizumab after a planned 6 month treatment interruption period. In clinical studies, serum transaminase elevations occurred during treatment and up to 4 months after the last dose of Zinbryta. Most patients had elevations that were asymptomatic and resolved spontaneously. An increased incidence of elevations of ALT or AST > 5 times the ULN was reported in Zinbryta-treated patients compared to placebo (4% versus <1%) or interferon beta-1a (intramuscular) (6% versus 3%). The incidence of discontinuation due to medicine related hepatic disorders was 5% in Zinbryta-treated patients and 4% in interferon beta-1a (intramuscular). Skin reactions In clinical studies Zinbryta increased the incidence of skin reactions [18% vs 13% (placebo); 37% vs 19% (interferon beta-1a (intramuscular))] and serious skin reactions [<1% vs 0% (placebo); 2% vs <1% (interferon beta-1a (intramuscular))] compared to placebo and interferon beta-1a (intramuscular). The most common skin reactions were rash, dermatitis, and eczema. The majority of patients had skin reactions that were mild or moderate in severity. Discontinuation due to skin reactions was 4% in Zinbryta-treated patients. Depression In clinical studies, Zinbryta increased the incidence of depression [5% vs 1% (placebo); 8% vs 6% (interferon beta-1a (intramuscular))]; the incidence of serious reactions of depression was <1% with Zinbryta. Infections In clinical studies, Zinbryta increased the incidence of infections [50% vs 44% (placebo) and 65% vs 57% (interferon beta-1a (intramuscular))] and serious infections [3% vs 0% (placebo); 4% vs 2% (interferon beta-1a (intramuscular))] compared to placebo and interferon beta-1a (intramuscular). The most common types of infections were upper respiratory tract infections and viral infections. The median duration was similar between the treatment groups. The rate of infections and serious infections did not increase over time. The majority of patients with infections continued on treatment with Zinbryta. Discontinuation of Zinbryta due to infections was <1%. Gastrointestinal disorders An increased incidence of serious colitis (<1%) was reported in patients treated with Zinbryta in clinical studies. Lymphadenopathy In clinical studies, Zinbryta increased the incidence of lymphadenopathy, with onset occurring throughout the treatment period. Discontinuation due to lymphadenopathy was <1% in Zinbryta-treated patients. The majority of patients with lymphadenopathy continued on treatment with Zinbryta, and the majority of cases resolved within 3 months. Immunogenicity In the DECIDE study (see section 5.1), patients were tested for anti-drug (daclizumab) antibodies at week 4 and approximately every 3 months thereafter. Treatment-emergent anti-drug antibodies and neutralising antibodies were observed in 19% (175/913) and 8% (71/913) of study patients, respectively. The majority of the treatment-emergent anti-drug antibodies responses were transient (12% [110/913]) and the remaining minority (7% [65/913]) were persistent. Among the evaluable patients, the majority of treatment-emergent neutralising antibody responses were transient (6% [56 of 913]) and 2% of patients (15 of 913) had persistent responses. Treatment-emergent anti-drug antibodies and neutralising antibodies responses predominantly occurred during the first year of treatment and their frequency declined with continued Zinbryta treatment. In patients with neutralising antibodies, daclizumab clearance was increased on average by 19% (see section 5.2). There was no apparent correlation of anti-drug antibodies or neutralising antibodies development to clinical response, adverse reactions, or pharmacodynamic profile of daclizumab. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: Ireland HPRA Pharmacovigilance Earlsfort Terrace IRL - Dublin 2 Tel: +353 1 6764971 Fax: +353 1 6762517 Website: www.hpra.ie e-mail: medsafety@hpra.ie United Kingdom Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard 4.9 Overdose Reported experience with overdose is limited. The safety of doses above 300 mg administered subcutaneously and 400 mg intravenously have not been evaluated. Doses up to this level were well tolerated with no evidence of acute toxicity. Potential adverse reactions beyond this level are expected to be consistent with the safety profile for daclizumab in MS patients. Management In case of overdose, patients may require medical attention and appropriate supportive treatment should be given. 5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: immunosuppressants, interleukin inhibitors, ATC code: L04AC01 Mechanism of action Daclizumab is a humanised IgG1 monoclonal antibody that binds to CD25 (IL-2Rα), and prevents IL-2 binding to CD25. Daclizumab modulates IL-2 signalling by blocking CD25-dependent, high-affinity IL-2 receptor signalling, resulting in higher levels of IL-2 available for signalling through the intermediate-affinity IL-2 receptor. Key effects of this IL-2 pathway modulation potentially related to the therapeutic effects of daclizumab in MS include selective antagonism of activated T-cell responses, and expansion of immunoregulatory CD56bright natural killer (NK) cells, which have been shown to selectively decrease activated T-cells. Together, these immunomodulatory effects of daclizumab are believed to reduce CNS pathology in MS and thereby reduce the occurrence of relapses and disability progression. Pharmacodynamic effects In clinical studies, the pharmacodynamic effects of Zinbryta 150 mg administered subcutaneously every 4 weeks were consistent with modulation of IL-2 signalling as evidenced by the rapid and sustained saturation of the target CD25 receptors on circulating T-cells and a sustained approximately 2-fold increase in serum IL-2 concentration. In addition, an increase in CD56bright NK cells and a decrease in regulatory T-cells (defined as CD4+CD127lowFoxP3+ T-cells) was observed within 2 weeks after the first dose, with a sustained 5-fold increase in CD56bright NK cells above baseline and an approximately 60% decrease in regulatory T-cells in the treatment phase, with a return to baseline levels approximately 20-24 weeks after the last dose. During Zinbryta treatment, mean cell counts for the major immune subsets (T, B, and NK cells) remained within normal ranges; total lymphocyte, T and B cell counts decreased on average ≤10% from baseline during the first year of treatment. Total lymphocyte counts returned to baseline levels approximately 8-12 weeks after the last dose of Zinbryta (150mg). Total lymphocyte counts <0.8x109 cells/L ([Common Terminology Criteria for Adverse Events – CTCAE] Grade 2; at least one measurement) occurred in 4% of placebo-treated and 5% of Zinbryta-treated patients in the SELECT study, and 9% of the interferon beta-1a (intramuscular)-treated and 8% of Zinbryta-treated patients in the DECIDE study. Total NK cell counts increased approximately 1.5-fold as a result of the change in CD56bright NK cells. Clinical efficacy and safety The efficacy of Zinbryta was demonstrated in two studies (SELECT and DECIDE) in patients with RMS. The SELECT study was double-blind, randomised, placebo-controlled, with either Zinbryta 150 mg (n=208), or 300 mg (n=209) versus placebo (n=204) every 4 weeks for 52 weeks. The DECIDE study was double-blind, randomised, parallel-group, active-controlled with Zinbryta 150 mg every 4 weeks (n=919) versus interferon beta-1a (intramuscular) 30 micrograms weekly (n=922), for a minimum of 2 to a maximum of 3 years (96 to 144 weeks). The study designs and baseline characteristics are presented in Table 3. Table 3: Study design and baseline characteristics for SELECT study and DECIDE study
Table 4: SELECT study clinical and MRI results (at 52 weeks)
MRI analyses used evaluable dataset for each endpoint; T1 Gd-enhancing: MRI intensive population Table 5 and Figures 1-2 show the results for the DECIDE study. Zinbryta significantly reduced the ARR and the risk of relapse, compared to interferon beta-1a (intramuscular)-treated patients. In addition, there was a statistically significant effect on 24 week confirmed disability progression in Zinbryta treated patients with a hazard ratio 0.73 [95% CI: 0.55, 0.98]. At week 96, Zinbryta demonstrated a statistically significant reduction in the number of new or newly enlarging T2 hyperintense lesions, the number of new T1 Gd-enhancing lesions and the mean number of new T1 hypointense lesions. In addition, Zinbryta reduced clinically meaningful worsening in the patient-reported physical impact of MS (≥7.5 point worsening from baseline to week 96 in the MSIS-29 physical score) compared to interferon beta-1a (intramuscular). Table 5: DECIDE study clinical and MRI results (96 to 144 weeks) (Values refer to results at 96 weeks, unless otherwise indicated.)
Hazard ratio for the risk of relapse. MRI analyses used evaluable dataset for each MRI endpoint. Subgroup analyses of the SELECT and DECIDE studies demonstrated a consistent effect of Zinbryta compared to placebo and interferon beta-1a (intramuscular) across subgroups defined by demographic and MS disease characteristics. In the DECIDE study subgroup analysis, there was a statistically significant reduction observed compared to interferon beta-1a (intramuscular) on ARR and the number of new or newly enlarging T2 hyperintense lesions across subgroups (gender, age, prior MS DMT therapy, and disease activity levels). Although the effect on disability progression was mainly seen in patients with baseline EDSS < 3.5, evidence of efficacy was shown in patients with relapsing secondary progressive MS (SPMS) as defined by baseline EDSS ≥ 3.5 and at least one of the three: confirmed 24 week worsening of EDSS, or ≥ 20% decline on Timed 25-foot Walk (T25FW), or, ≥ 20% decline on 9-Hole Peg Test (9-HPT). Efficacy in patients with highly active disease Highly active disease was defined as follows: • Patients with 2 or more relapses in 1 year, and with 1 or more Gd-enhancing lesions on brain MRI, or • Patients who had failed to respond to a full and adequate course (at least 1 year) of prior DMT treatment, having had at least 1 relapse in the previous year while on therapy, and at least 9 T2 hyperintense lesions in cranial MRI or at least 1 Gd-enhancing lesion, or having an unchanged or increased relapse rate in the prior year as compared to the previous 2 years. Clinical trial data from the DECIDE study demonstrated consistent treatment effects in the highly active disease subgroup. Compared with interferon beta-1a intramuscular (n=440), Zinbryta (n=404) led to reductions on ARR (rate ratio 0.52 [95% CI: 0.42, 0.64], p<0.0001), number of new or newly enlarging T2 hyperintense lesions (lesion mean ratio 0.46 [95% CI: 0.37, 0.57], p<0.0001), and 24 weeks confirmed disability progression (hazard ratio 0.60 [95% CI: 0.40, 0.89], p=0.012). Figure 1: Percentage of patients relapse-free (DECIDE study) Figure 2: Proportion of patients with 24 week confirmed disability (DECIDE study) Paediatric population The European Medicines Agency has deferred the obligation to submit the results of studies with Zinbryta in one or more subsets of the paediatric population in treatment of multiple sclerosis (see section 4.2 for information on paediatric use). 5.2 Pharmacokinetic properties Daclizumab pharmacokinetics are well described by a two-compartment model with first-order absorption and elimination. Absorption Following subcutaneous administration of daclizumab, the median time to reach maximum serum concentrations (Tmax) ranged from 5 to 7 days. The absolute bioavailability of daclizumab 150 mg subcutaneously administered was approximately 90% based on a cross-study population pharmacokinetic analysis of subcutaneous and intravenous dosing. Distribution Following subcutaneous administration of daclizumab 150 mg every 4 weeks, steady-state serum daclizumab concentrations were achieved by the 4th dose and daclizumab accumulated to a level approximately 2.5-fold compared to a single dose. At steady state, daclizumab mean maximum serum concentration (Cmax), minimum serum concentration (Cmin) and area under the serum concentration-time curve over the dosing interval (AUCtau) values were approximately 30 micrograms/mL, 15 micrograms/mL and 640 day*micrograms/mL, respectively, with inter-patient variability (% CV) of approximately 40%. Based on the cross-study population pharmacokinetic analysis, the steady-state volume of distribution of daclizumab is 6.34 L in a patient with a body weight of 68 kg (approximate median of evaluated patients). This small volume of distribution indicates that daclizumab is primarily confined to the vascular and interstitial spaces. Biotransformation The exact metabolic pathway for daclizumab has not been characterised. As an IgG1 monoclonal antibody, daclizumab is expected to undergo catabolism to peptides and amino acids in the same manner as endogenous IgG. Daclizumab is not expected to undergo metabolism by hepatic enzymes such as CYP isoenzymes (see section 4.5). Elimination As an IgG1 monoclonal antibody, daclizumab is not expected to undergo renal elimination. Based on the cross-study population pharmacokinetic analysis, the clearance of daclizumab is 0.212 L/day with a terminal half-life value of approximately 21 days. Daclizumab clearance in patients who developed neutralising antibodies was, on average, 19% higher (see section 4.8 Immunogenicity). Linearity/non-linearity Consistent with results from individual studies, a cross-study population pharmacokinetic analysis indicated that daclizumab exposure is more than dose-proportional in the 50 mg to 100 mg subcutaneous dose range and is dose proportional in the 100 mg to 300 mg subcutaneous dose range. Pharmacokinetic/pharmacodynamic relationship(s) Within the studied regimens of daclizumab 150 mg and 300 mg administered subcutaneous every 4 weeks in MS patients, there was no clear relationship between daclizumab exposure and clinical efficacy endpoints (ARR, T2 lesions and Gd-enhancing lesions) or safety endpoints of interest (serious infection status, moderate or severe cutaneous adverse reaction, and AST/ALT > 5 times the ULN). Special populations Renal or hepatic impairment No studies were conducted to evaluate daclizumab pharmacokinetics in patients with renal or hepatic impairment. Daclizumab is not expected to undergo renal elimination or metabolism by hepatic enzymes (see section 4.2). Weight Based on the cross-study population pharmacokinetic analysis, body weight accounted for less than 40% of the inter-patient variability in daclizumab clearance. No meaningful differences in clinical efficacy or safety were observed among the subgroups of MS patients by weight quartile in the DECIDE study. Age and gender Based on the cross-study population pharmacokinetic analysis, daclizumab pharmacokinetics were not influenced by age (range: 18 to 66 years; n=1670) or gender (n = 567 males and 1103 females). Race No pharmacokinetic differences were observed between Japanese and Caucasian healthy volunteers. 5.3 Preclinical safety data Preclinical safety studies were conducted in cynomolgus monkeys due to species specificity of daclizumab binding only to human or primate CD25. Carcinogenesis Carcinogenicity studies with daclizumab have not been conducted. In two 9 month studies in monkeys there were no pre-neoplastic or neoplastic tissue observed. Mutagenesis Genotoxicity studies have not been conducted. Reproductive toxicity Daclizumab did not affect reproductive capacity in female and male cynomolgus monkeys (AUC in females and males up to 85 and 100 times higher than the exposure at the clinical dose respectively). There was no effect on foetal development and no evidence of teratogenicity. Daclizumab had no effect on peri- and post-natal development from birth to up to 6 months in the offspring. Exposures (AUC) in these studies ranged from 55 to 140 times that observed with the clinical dose. Daclizumab was detected in the milk of 11/14 lactating monkeys at levels that were <0.122% of the maternal serum levels, with no adverse reactions observed in the off-spring. Toxicology In two 9 month studies conducted in cynomolgus monkeys daclizumab was subcutaneously administered at bi-weekly doses of 10-200 mg/kg. Chronic administration of daclizumab at all doses increased the incidence of skin findings (compared to those observed in control animals). These findings (dry, red raised patchy areas of the skin, as compared to controls, that correlated microscopically with acanthosis/hyperkeratosis and sub-acute to chronic inflammation) were characterised predominantly as mild to moderate, with one case assessed as severe. A dose dependent increase in incidence of microglial aggregates above background was observed in the brain and spinal cord of monkeys treated with ≥35 mg/kg, (AUC 27 times higher than the clinical dose). Following a recovery period of up to 12 weeks, there was evidence of reversibility. Microglial aggregates in monkeys did not increase in incidence or severity with increased duration of dosing and were not associated with neuronal damage or neurobehavioral effects. A small subset of microglial aggregates were associated with microhaemorrhage but with no evident functional sequelae in monkeys. In vitro investigative studies suggest that microglial aggregates are not due to a direct effect of daclizumab on microglial cells but are likely to be attributable to an increase in local IL-2 bioavailability. The clinical relevance of microglial aggregates is unknown, however no deleterious neurologic effects attributed to the microscopic change have been observed in monkeys. 6. Pharmaceutical particulars 6.1 List of excipients Sodium succinate Succinic acid Sodium chloride Polysorbate 80 Water for injections 6.2 Incompatibilities In the absence of compatibility studies, this medicinal product should not be mixed with other products. 6.3 Shelf life 3 years. Zinbryta can be stored at room temperature (up to 30°C) in the original pack for 30 days. Do not place Zinbryta back into the refrigerator after warming to room temperature. If Zinbryta has been outside of the refrigerator for more than a total of 30 days or if you are not sure how long Zinbryta has been at room temperature, it should be discarded. 6.4 Special precautions for storage Store in a refrigerator (2°C-8°C). Do not freeze. Store in the original package in order to protect from light. For additional information on storage at room temperature, see section 6.3. 6.5 Nature and contents of container Pre-filled syringe made of glass (Type 1) with a rubber stopper and thermoplastic rigid needle shield containing 1 mL of solution. A 29 gauge, 0.5 inch staked needle is pre-affixed to the syringe. Pack sizes: - Pack containing one 150 mg pre-filled syringe. - 3 month multipack containing three 150 mg pre-filled syringes (3 boxes containing 1 syringe each). A pre-filled syringe of Zinbryta is contained within a spring-powered pen injector called Zinbryta Pen. The syringe inside the pen is a pre-filled syringe made of glass (Type 1) with a rubber stopper and thermoplastic rigid needle shield, containing 1 mL of solution. A 29 gauge, 0.5 inch staked needle is pre-affixed to the syringe. Pack sizes: - Pack containing one 150 mg pre-filled pen. - 3 month multipack containing three 150 mg pre-filled pens (3 boxes containing 1 pen each). Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling Any unused medicinal product or waste material should be disposed of in accordance with local requirements. 7. Marketing authorisation holder BIOGEN IDEC Limited Innovation House 70 Norden Road Maidenhead Berkshire SL6 4AY United Kingdom 8. Marketing authorisation number(s) EU/1/16/1107/001 EU/1/16/1107/002 EU/1/16/1107/003 EU/1/16/1107/004 9. Date of first authorisation/renewal of the authorisation Date of first authorisation: 1st July 2016 10. Date of revision of the text 07/2016 Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
达克珠单抗注射剂|Zinbryta（daclizumab solution for injection）简介：每月只一次注射的多发性硬化症药物Zinbryta获欧盟批准上市2016年7月6日，百健（Biogen）和艾伯维（AbbVie）合作开发的每月注射一次的多发性硬化症（MS）单抗药物Zinbryta（daclizumab，达克珠单抗）获Z ... 责任编辑：p53
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