Sammanfattning biverkningar
exklusive bekräftade/misstänkta covid-19-händelser1,a
SLE-nefrit: Gazyvaro i kombination med mykofenolatmofetil (MMF) är indicerat för behandling av vuxna patienter med aktiv SLE-nefrit av klass III eller IV, med eller utan samtidig klass V.
Clinical use:
The indication is granted market authorization based on objective response rate (ORR) demonstrated in a single-arm Phase II trial. Overall survival (OS) benefit in a single-arm trial cannot be confirmed.
In the pivotal trial, the majority of the clinical responses occurred within 16 weeks. Benefit of continued treatment should be regularly assessed, with the optimal duration of therapy varying for each individual patient.
Distribution Restrictions: ERIVEDGE is only available through a controlled distribution program called the ERIVEDGE Pregnancy Prevention Program (EPPP). For more information please contact the EPPP at 1-888-748-8926 or log onto rocheproplus.ca/en/products-resources/erivedge.html.
Geriatrics (≥65 years of age): Elderly patients should be treated with caution and monitored for adverse events.
Pediatrics (<18 years of age): The safety and efficacy of ERIVEDGE in pediatric patients has not been established. Irreversible premature fusion of the epiphyses and precocious puberty have been reported in pediatric patients exposed to ERIVEDGE. Premature fusion can progress after discontinuation of treatment. Due to safety concerns ERIVEDGE is contraindicated in children and adolescents aged below 18 years.
Contraindications:
Female patients who are pregnant or at risk of becoming pregnant
Breastfeeding female patients
Female patients of childbearing potential (FCBP) and male patients who do not comply with the ERIVEDGE Pregnancy Prevention Program
Children and adolescents aged less than 18 years of age
Patients who are hypersensitive to vismodegib or to any ingredient in the formulation
Most serious warnings and precautions:
Embryo-fetal death or severe birth defects: Can cause severe malformations, including craniofacial anomalies, midline defects and limb defects when administered to a female who is pregnant. Must not be used during pregnancy.
Effects on post-natal development: Irreversible premature fusion of the epiphyses (EPF) and precocious puberty have been reported in pediatric patients exposed to ERIVEDGE. In some cases of EPF, fusion progressed after drug discontinuation.
Renal impairment: The safety and efficacy of ERIVEDGE in patients with severe renal impairment have not been studied. No dedicated clinical studies have been conducted to evaluate the effect of mild, moderate and severe renal impairment on the pharmacokinetics of vismodegib.
Hepatic impairment: ERIVEDGE is not recommended for use in patients with severe hepatic impairment since limited data are available in these patients. ERIVEDGE should be used with caution in patients with mild and moderate hepatic impairment.
Other relevant warnings and precautions:
Effects on post-natal development
Blood donation: Patients must not donate blood while on treatment and for 24 months after discontinuation
Patients with advanced BCC (aBCC) have an increased risk of developing cutaneous squamous cell carcinoma (cuSCC). Cases of cuSCC have been reported in aBCC patients treated with ERIVEDGE. All patients should be monitored routinely while taking ERIVEDGE
Cardiovascular-related events
Decreased appetite, decreased weight and dehydration
Electrolyte abnormalities
Hepatotoxicity
Patients with a history of pancreatitis or gallbladder disease
Gastrointestinal-related events
Anaemia and lymphopenia
Grade 1 hypersensitivity
Arthralgia, back pain, muscle spasms, fractures, and elevated creatine phospohokinase (CPK) measurements reported
Syncope, dysgeusia and ageusia
Psychiatric disorders
Renal disorders and cases of renal failure have been observed in patients treated with ERIVEDGE
Amenorrhea has been observed in clinical trials in 30% of FCBP (Female of Childbearing Potential). Potential to impair fertility in patients
Blood work monitoring
For more information:
Please consult the Product Monograph for important information relating to warnings and precautions, adverse reactions, drug interactions, and dosing information that has not been discussed in this piece.
The Product Monograph is also available by calling us at 1-888-762-4388.
Verkningsmekanism
Obinutuzumab: En typ II anti-CD20-antikropp
•Obinutuzumab är en rekombinant, humaniserad, glykomodifierad typ II anti-CD20 monoklonal antikropp godkänd och indikerad för kombinationsbehandling av Kronisk lymfatisk leukemi (KLL) 2014 och follikulärt lymfom (FL)1,2
•Obinutuzumab binder till CD20 uttryckt på B-celler och leder till celldöd via:3
•Direkt celldöd (apoptos)
•Antikroppsberoende cellmedierad cytotoxicitet
•Antikroppsberoende cellmedierad fagocytos
•Obinutuzumab har visat överlägsen B-cellsdepletion jämfört med rituximab, tack vare:
•Dess glykomodifiering: Säkerställer större antikroppsberoende cellmedierad cytotoxicitet genom förbättrad bindningsaffinitet till immuneffektorceller4-6
•Typ II-bindningskonformationen: Ökar direkt celldöd, med minskad internalisering och mindre beroende av komplementberoende cytotoxicitet4-6
•Obinutuzumab har visats hämma B-celler i både perifert blod och lymfatisk vävnad4-7
Referenser:
1. European Medicines Agency (EMA). October 2024. https://www.ema.europa.eu/en/documents/product-information/gazyvaro-epar-product-information_en.pdf. (Accessed June 2025);
2. US Food & Drug Administration (FDA). July 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125486s029lbl.pdf. (Accessed June 2025);
3. Hernandez J, et al. https://www.nature.com/articles/d42473-018-00278-8. (Accessed June 2025);
4. Mössner E, et al. Blood. 2010;115:4393–4402;
5. Herter S, et al. Mol Cancer Ther. 2013;12:2031–2042;
6. Tobinai K, et al. Adv Ther. 2017;34:324–356;
7. Looney CM, et al. Transplant Direct 2023;9:e1436.
Studiedesign
Fas III REGENCY (NCT04221477) studien1
.260303?qlt=85&ts=1772552719162&dpr=off)
aStandard treatment of MMF plus glucocorticoids;
bPatients with an adequate treatment response at Week 76 continued to receive blinded infusions every 6 months starting at Week 80, until study unblinding;
cPatients with inadequate treatment response at Week 76 or with loss of response during blinded treatment after Week 80 could enter open-label treatment;
dPatients were followed through Week 76 and for at least 12 months from the last dose of obinutuzumab or placebo;
Inklusionskriterier1
•Vuxna 18-75 år
• Klassifikationskriterier för SLE enligt ACR
• Aktiv ISN/RPS klass III eller IV SLE-nefrit med eller utan klass V, baserat på njurbiopsi utförd ≤6 månader före eller under screening
• Positivt anti-nukleärt antikroppstest (≥1:80 pm Hep-2 celler eller ≥1 motsvarande anti-nukleärt antikroppstest)
• ≥1 dos pulsdos metylprednisolon IV (≥250 mg) eller motsvarande behandling för den nuvarande episoden av aktiv LN från 6 månader före screening till och med dag 1 före den första infusionen
Exklusionskriterier1
•eGFR <30 mL/min/1,73 m2 kroppsyta
• UPCR <1 g/g
• ESKD2 som kräver dialys eller transplantation
• Aktiv infektion
• Anti-CD20-terapi <9 månader före eller under screening
• Cyklophosphamid, takrolimus, cyklosporin eller voklosporin ≤2 månader före eller under screening
Referenser:
1. Furie RA, et al. N Engl J Med. 2025;392:1471-1483.
2. ESKD, end-stage kidney disease
Effekt
Primär endpoint – komplett respons vid v. 761
aStandard treatment of MMF plus glucocorticoids;
bTreatment failure was defined as the occurrence of one or more of the following: New ESKD or need for chronic dialysis or renal transplantation; clinically significant, sustained worsening of UPCR and/or eGFR from Week 24 onward that led the investigator to conclude that the patient had failed the randomized treatment regimen; receipt of rescue therapy, except for glucocorticoid-only rescue.
Sekundär endpoint
CRR vid v. 76 med prednison ≤7.5 mg/dag mellan v. 64 och v. 761
aStandard treatment of MMF plus glucocorticoids.
Referenser
1. Furie RA, et al. N Engl J Med. 2025;392:1471-1483.
aThe safety population included all the patients who received any infusion of obinutuzumab or placebo in a blinded manner; the patients were grouped according to the infusion that was administered, regardless of the randomly assigned study group;
bStandard treatment of MMF plus glucocorticoids.
Referenser
1. Furie RA, et al. N Engl J Med. 2025;392:1471-1483.
GAZYVARO® (obinutuzumab), 1000 mg (25 mg/ml) koncentrat till infusionsvätska, lösning. Monoklonal antikropp L01FA03 (Rx,EF).
Indikationer: KLL: GAZYVARO i kombination med klorambucil är indicerat för behandling av vuxna patienter med tidigare obehandlad kronisk lymfatisk leukemi (KLL) och med komorbiditeter där fulldos fludarabinbaserad behandling inte är lämplig. Follikulärt lymfom (FL): GAZYVARO i kombination med kemoterapi, följt av underhållsbehandling med GAZYVARO hos patienter som svarat på behandling, är indicerat för behandling av tidigare obehandlade patienter med avancerat follikulärt lymfom. GAZYVARO i kombination med bendamustin följt av underhållsbehandling med GAZYVARO är indicerat för behandling av patienter med follikulära lymfom (FL) som inte svarat eller som har progredierat under eller upp till 6 månader efter behandling med rituximab eller rituximabinnehållande behandling. SLE-nefrit: GAZYVARO i kombination med mykofenolatmofetil (MMF) är indicerat för behandling av vuxna patienter med aktiv SLE-nefrit av klass III eller IV, med eller utan samtidig klass V.
Kontraindikationer: Överkänslighet mot den aktiva substansen eller mot något hjälpämne som ingår i lösningen.
Varningar och försiktighet: För att förbättra spårbarheten för biologiska läkemedel ska läkemedlets namn och tillverkningsstasnummer dokumenteras. KLL och FL: Infusionsrelaterade reaktioner, överkänslighetsreaktioner, tumörlyssyndrom (TLS), neutropeni, trombocytopeni, koagulationsrubbningar inklusive disseminerad intravasal koagulation (DIC), hjärtproblem, infektioner, hepatit B-reaktivering, progressiv multifokal leukoencefalopati (PML) och immunisering. SLE-nefrit: infektioner, neutropeni, infusionsrelaterade reaktioner och immunisering. För ingående beskrivning av varningar och försiktighet se www.fass.se.
Datum för översyn av produktresumén: 2025-12-04.
För fullständig information vid förskrivning, produktresumé och aktuella priser, se
www.fass.se.
Hälso- och sjukvårdspersonal uppmanas att rapportera varje misstänkt biverkning. Rapporteringen ska göras till Läkemedelsverket, www.lakemedelsverket.se eller direkt till Roche på sverige.safety@roche.com.
Roche AB | Box 1228 | 171 23 Solna
Tel 08-726 12 00
www.roche.se