Biosimilarer ur ett svenskt perspektiv Bertil Jonsson Medical Products Agency
Vad? Godkännande Visst det finns riktlinjer Riskhantering (RMP, PhV) Original och kopia Uppföljning i Sverige Spårbarhet PhV Och varför jag?
Comparability. Assay Sensitivity! Regulatory ( LV ) Kvalitet In vitro assays Djurmodeller Human kinetik Human dynamik Effekt Säkerhet (immunogenicitet) Omvärlden Kvalitet In vitro assays Djurmodeller Human kinetik Human dynamik Effekt/Säkerhet
En bioteknologivärderas syn på biosimilardokumentation Klinisk effekt Kliniska säkerhetshetsstudier (Immunogenicitet) PD-studier Sedvanlig kvalitetsdokumentation för biologiska produkter + PK-studier (kliniska) nonclinical Jämförande studier mellan biosimilar och orginalprodukt
Studiekrav För att uppnå en indikation, stand alone mkt enklare. Principen är extrapolering, men kan kräva kompletterande bryggande studier, typ dynamik, om till annat terapiområde. Idag vanligen en effekt/säkerhet ekvivalensstudie + bryggande studie(r) till annan väsenskild indikation.
Anekdoter Original produkten förändras över tid Hinner biosimilaren med? Biobetter Renare, ja. Men inte.. PK ekvivalens 80 125% 82 95%? Effekt Icke godkänd indikation (e.g. neoadjuvant terapi)? Extrapolera? Säkerhet Öppen studie, skillnad i biverkningar
Biosimilarer ansökta i EU
Säkerhet Safety specification Describes the safety profile of the product as Important identified risks, Important potential risks, and missing information Pharmacovigilance plan Describes how the safety of the product should be followed up routine additional e.g. non-interventional studies Risk minimisation plan routine (product information) additional e.g. educational material, patient alert card
Important identified risk Important potential risk Missing information Remsima (Remicade) - Safety specification HBV reactivation; Congestive heart failure Opportunistic infections Serious infections including sepsis (exclud opportunistic infections, TB) Tuberculosis Seum sickness (delayed hypersensitivity reactions ) Haematologic reactions Systemic lupus erythematosus/lupus-like syndrome Demyelinating disorders Lymphoma (not HSTCL) Hepatosplenic T cell lymphoma (HSTCL) Intestinal or perianal abscess (in Crohn s disease) Serious infusion reactions during a re-induction regimen following disease flare Sarcoidosis/sarcoid-like reactions Paediatric malignancy Leukaemia Malignancy (excluding lymphoma) Colon carcinoma/dyplasia (in ulcerative colitis) Skin cancer Pregnancy exposure Infusion reaction associated with shortened infusion duration (in RA) Bowel stenosis, stricture, obstruction (in Crohn s disease) Long-term safety in adult patients with ulcerative colitis, psoriatic arthritis, or psoriasis Long-term safety in children with Crohn s disease and ulcerative colitis Long-term safety in children Safety in very young children (<6 years) Use of infliximab during lactation Lack of efficacy Hypersensitivity
Ongoing Phase I-III studies Remsima PhV plan Registry CT-P13 4.2: Observational, Prospective Cohort Study; Evaluate Safety & Efficacy of Remsima in Patients with RA (EU & Korea) British Society for Rheumatology Biologics Register Rheumatoid Arthritis Registry CT-P13 4.3: An observational, prospective cohort study to evaluate safety and efficacy of Remsima in CD, UC (EU, Korea) Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) The PRAC* recommended participation in other available European databases with RA patients (e.g. in Sweden and Spain) PRAC: PhV Risk Assessment Committee
Remsima Risk minimisation plan Routine product information (SmPC, Package leaflet) including pointing out importance to report brand name Additional patient alert card (TB, CHF) educational material to all prescribers; focus TB / infections educational material to prescribers for patients with pediatric inflammatory bowel diseases
Säkerhet/uppföljning Klassrelaterade PhV aktiviteter. Allmän PhV som för alla nya läkemedel, t.ex. periodic safety update reports. Immunogenicitetstudier (register) för alla biosimilarer (?). Som för alla biologics spårbarhet på batchnivå Gäller också i Sverige.