• recombinant human interferon alpha
• indicated for: hairy cell leukemia, AIDS-related Kaposi's sarcoma, chronic myelogenous leukemia, chronic hepatitis B and C, genital warts, papillomavirus
• major adverse reactions: fever, myalgia and headache; flu like symptoms

• consensus alpha interferon, analog
• indicated for: treatment of adult chronic hepatitis C
• it was the first second generation interferon
• side effects: flu-like symptoms, including fever, headache, myalgia, stiffness, fatigue
• pts on long-term therapy suffer depression and irritability that can be severe

• pegylated recombinant human interferon alfa
• indicated for: chronic hepatitis C alone or with ribavirin
• pegylation allows once/week dosing

• recombinant human interferon beta
• indicated for: relapsing, remitting multiple sclerosis and secondary progressive multiple sclerosis
• Delivery: single-use, pre-filled syringes
• adverse reactions: flu-like symptoms

• recombinant human interferon gamma
• indications: reduces frequency/severity of infections associated with chronic granulomatous disease; delays disease progression in severe, malignant osteopetrosis
• administered by subq injection 3x weekly at 50mcg/m²

interferon drugs

(brand names)

interferon drugs

(generic names)

• Interferon alpha 2a, 2b, n1, n3
• interferon alfacon-1
• peginterferon alfa 2a, 2b
• interferon beta- 1b, 1a
• interferon gamma-1b

Interleukins and Regulators

(brand name)

• Proleukin
• Neumega
• Kineret

• aldesleukin
• oprelvekin
• anakinra

• recombinant human interleuki-2
• indications: metastatic malignant melanoma, metastatic renal cell carcinoma
• severe toxicity inc. caplillary leak syndrome, cardiac arrythmias, angina, MI, respiratory failure, GI bleeding, and kidney failure

• thrombopoietic growth factor, IL-11
• indications: prevention of chemotherapy-associated thrombocytopenia
• 50mcg/kg SC every day for adults for 14-21 days

• selective interleukin-1 receptor antagonist
• Indication: rheumatoid arthritis alone or with other DMARDs
• 100mg/day SC; monitor neutrophil count for 3 months

oligonucleotide drugs

(brand names)

• Vitavene
• Macugen

oligonucleotide drugs

(generic names)

• fomivirsen sodium
• pegaptanib sodium

• antisense
• siRNA
• aptamers

• structure: 21-base phosphorothionate oligonucleotide
• indications: cytomegalovirus retinitis in HIV pts intolerant or nresponsive to other approved treatments
• 1st FDA approved, believed to act by an antisense mechanism (blocking synthesis of the CMV immediate early protein 1E2), it is no suspected to act as an interferon inducer
• injected directly into the vitreous eye fluid

• pegylated 28-mer oligonucleotide
• indication: neovascular (wet) age-related macular degeneration
• first aptamer drug, which binds to and inactivates extracellular VEGF
• injected directly into the vitreous fluid of the eye

• dimeric fusion protein of TNF-alpha receptor + IgG1 Fc
• Indication: reduce signs and symptoms of ankylosing spondylitis; plaque psoriasis; psoriatic arthritis; adult and juvenile RA alone and with methotrexate
• not to be used in patients with serious infection or sepsis; cost $10,400/yr

Pseudoantibodie drugs

(generic names)

• etanercept
• alefacept
• abatacept

pseudoantibody drugs

(brand name)

• Enbrel
• Amevive
• Orencia

• humanized monoclonal ab against CD33 attached to calicheamicin via a thiol-cleavable linker
• indication: CD-33 positive acute myeloid leukemia
• first immunotoxin approved; calicheamicin is a far too cytotoxic antibody to be useful in cancer chemotherapy on its own

denileukin difitox

• diptheria toxin fragments A and B fused to an interleukin-2 fragment
• Indication: CD25 positive persistent/recurrent cutaneousT-cell lymphoma
• first fusion toxin to be approved; its an orphan drug costing $25-50 thous. per treatment

Interleukin drugs

(brand name)

• Proleukin
• Neumega
• Kineret

Interleukin drugs

(generic name)

• aldesleukin
• oprelvekin
• anakinra

Colony stimulating factor drugs

(generic names)

• Filgrastim
• Pegfilgrastim
• sargramostim

Colony stimulating factor drugs

(brand name)

• Neupogen
• Neulasta
• Leukine/Prokine

• stimulates neutrophil production, but has a longer half life than filgrastim
• pegylated filgrastim
• indication: decreases chemotherapy-associated neutropenia
• modified filgrastim with lower clearance rates and increased circulation lifetimes

coagulation factor drugs

(generic name)

• moroctocog alfa
• eptacog alfa
• nonacog alfa

coagulation factor drugs

(brand name)

• Helixate-P/ Kogenate/ Recombinate/ Refacto/ Advate/ Bioclate
• NovoSeven
• BeneFIX

Growth factors turned into drugs

(generic names)

• becaplermin
• palifermin
• Bone morphogenic protein-2

Growth factors turned into drugs

(brand name)

• Regranex Gel
• Kepivance

• indication: diabetic ulcers of the lower limbs and feet that extend into the subcutaneous layer or beyond
• recombinant B chain of the homodimer of human platelet-derived growth factor synthesized in Sacchromyces cerevisiae (yeast)
• PDGF stimulates mitosis and movement offibroblasts, neutrophils and macrophages, which are all involved in tissue repair.Fibroblasts stimulated to secrete collagenase, which is used in tissue remodeling (stage in wound healing)

• indication: reduces the chances of developing severe mucositis (injury to the cells lining the mouth) and shortening recovery time from severe mucositis in patietns with cancer who recive high doses of chemotherapy and radiation therapy followed by stem cell rescue
• recombinant human keratinocyte growth factor, which stimulates the growth of cells in tissue such as skin and the surface layer of the mouth, stomach lining, and colon

• indication: spinal fusion procedures in skeletally mature pts with degenerative disc disease
• Marketed by Medtronic
• BMP-2 is produced in E.coli at Wyeth
• signaling for osteogenesis occurs through receptor serine threonine kinases

• Follicle Stimulating Hormone:
  • Follitropin alfa (Gona-F)
  • Follitropin beta (Follistim)
• Luteinizing hormone:
  • Lutropin alfa (Luveris)
• Human choriogonadotropin:
  • Choriogonadotropin alfa (Ovidrel)

• activatedprotein C acute phase protein
• indication: severe sepsis associated with organ dysfunction and high risk of death
• binds to high affinity interleukin-2 receptor on activated T_helper cells
• acute phase proteins produced by body in response to infection, and are normally purified from pleural fluid
• sepsis is the leading cause of bankruptcy in biotech companies

• no FDA approved drugs yet
• most research for oligonucleotide drugs is aimed at exploiting natural mechanism that specifically turns off protein synthesis with oligonucleotides
• short interfering RNA turns out to work much better than antisense with RNAse H- typically siRNA 10 to 200 x more active

• chimeric Fab fragment that binds to glycoprotein IIb/IIIa receptor of platelets blocking aggregation
• indications: adjunct to angioplasty (PCI); unstable angina during PCI, MI
• contraindicated for major surgery, trauma or other bleeding risk within 6 weeks

• human tissue plasminogen activator (tPA, an enzyme

indication: acute MI, stroke, and pulmonary embolism

causes clot lysis by converting plasminogen into plasmin by limited proteolysis. It binds to fibrin in blood clots, and is activated 400x, allowing it to preferentially lyse clots with limited systemic proteolysis 

• second generation thrombolytic
• contains only 2 of the domain: protease and kringle-2. since it is smaller it will diffuse faster.

• the same as alteplase but has 6 amino acid substitutions specifically designed to prolong its half-life, enabling single bolus dosing, and increased specificity for fibrin
• substitution of threonine 103 w/ asp, asp117 w/ glu, and amino acids 296-299 with tetr-alanine
• results in less disturbance of the coagulation system

• pegylated analog of human growth hormone
• indication: acromegaly
• 1st GH receptor antagonist produced: contains 191 amino acid residues to which 4-6 PEG polymers are covalently bound

• pegylated erythropoietin
• indication: treatment of anemia associated with chronic kidney disease
• allows once per month dosing

• cytokine that stimulates red blood cell production
• indication: anemia in chemotherapy and AZT Tx, chronic renal failure; reduces red blood transfusions in surgery
• first biotechnology blockbuster with US sales >$1 billion/yr;potential drug of abuse in endurance athletes

• second generation erythropoetin
• highly sialylated EPO
• indication: anemia in chronic renal failure, chronic renal insufficiency and chemotherapy
• Darbepoetin achieves a 3x longer circulating half-life due to increased sialylation