10.6 Biologics & Biosimilars
Biologics are complex molecules produced by living organisms, including antibodies, vaccines, and gene therapies. Biosimilars are highly similar versions of approved biologics.
Monoclonal Antibodies
Nomenclature
- • -omab: Mouse antibody
- • -ximab: Chimeric (human-mouse hybrid)
- • -zumab: Humanized (mostly human)
- • -umab: Fully human
- Example: Infliximab (chimeric), adalimumab (human)
Mechanisms
- • Target cell surface receptors or circulating proteins
- • Antibody-dependent cell cytotoxicity (ADCC)
- • Complement-dependent cytotoxicity (CDC)
- • Receptor blockade or agonism
Types of Biologics
Therapeutic Antibodies
Cancer Therapy
- • Rituximab (anti-CD20): Lymphomas
- • Trastuzumab (anti-HER2): Breast cancer
- • Bevacizumab (anti-VEGF): Angiogenesis inhibitor
- • Pembrolizumab (anti-PD-1): Checkpoint inhibitor
Autoimmune/Inflammatory
- • Infliximab (anti-TNF-α): RA, IBD
- • Adalimumab (anti-TNF-α): Multiple indications
- • Ustekinumab (anti-IL-12/23): Psoriasis
- • Secukinumab (anti-IL-17): Psoriatic arthritis
Vaccines
Live-Attenuated
- • MMR, varicella, rotavirus
- • Strong immunity
- • Contraindicated in immunocompromised
Inactivated/Subunit
- • Influenza, hepatitis A/B, HPV
- • Safer in immunocompromised
- • May need boosters
mRNA Vaccines
- • COVID-19 (Pfizer, Moderna)
- • Encode antigen protein
- • Novel platform
Gene Therapy
Ex Vivo
- • CAR-T cell therapy (tisagenlecleucel)
- • Cells modified outside body, then reinfused
- • For hematologic malignancies
In Vivo
- • Onasemnogene (Zolgensma) for SMA
- • AAV vector delivers gene directly
- • One-time treatment
Biosimilars
Regulatory & Clinical Considerations
Definition:
Biosimilars are highly similar to an approved reference biologic, with no clinically meaningful differences in safety, purity, or potency. NOT identical (unlike generic small molecules).
Approval Process:
- • Analytical studies (structure, function)
- • Pharmacokinetic/pharmacodynamic studies
- • Limited clinical trials (demonstrate similarity)
- • Less extensive than original biologic approval
Examples:
- • Filgrastim-sndz (biosimilar of Neupogen/filgrastim)
- • Infliximab-dyyb (biosimilar of Remicade)
- • Bevacizumab-awwb (biosimilar of Avastin)
Benefits:
- ✓ Lower cost (15-35% reduction)
- ✓ Increased access to biologics
- ✓ Comparable efficacy and safety
Special Considerations for Biologics
Immunogenicity
- • Formation of anti-drug antibodies (ADAs)
- • Can reduce efficacy or cause hypersensitivity
- • Higher risk with chimeric vs humanized antibodies
- • May require switching to different biologic
Administration & Storage
- • Most require refrigeration (2-8°C)
- • IV infusion or subcutaneous injection
- • Cannot be taken orally (degraded in GI tract)
- • Often require premedication (antihistamines, steroids)
Infection Risk
- • Immunosuppression increases infection risk
- • Screen for latent TB before TNF-α inhibitors
- • Avoid live vaccines during therapy
- • Monitor for opportunistic infections
Cost Considerations
- • Extremely expensive ($20,000-$500,000/year)
- • Biosimilars offer cost savings
- • May require prior authorization
- • Patient assistance programs often available