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”)
”Omvärlden”
Kvalitet
In vitro assays
Kvalitet
– Djurmodeller
– Human kinetik
Human dynamik
• Effekt
– Säkerhet
(immunogenicitet)
In vitro assays
Djurmodeller
Human kinetik
Human dynamik
Effekt/Säkerhet
En bioteknologivärderas syn på
biosimilardokumentation
Kliniska
säkerhetshetsstudier
Klinisk effekt
PD-studier
(Immunogenicitet)
PK-studier
(kliniska)
nonclinical
Sedvanlig kvalitetsdokumentation för
biologiska produkter
+
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
Remsima (Remicade) - Safety specification
Important
identified risk
Important
potential risk
Missing
information
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
Remsima – PhV plan
•
Ongoing Phase I-III studies
•
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.