Marketing of Peptide, Proteins,

Author: Sasan NasoohiFunction : Sales Manager Schering PloughDate : Nov 08Presented to Ph.D. students of Faculty of Pharmacy of Tehran University

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Proteins, eventually !!

•Our genetic material speaks the tale of proteins

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Proteins: disease and remedy

• Loss in protein production or functionality might lead to serious diseases – Diabetes Mellitus

• Proteins might mediates diseases as well– C-reactive protein mediates cardiovascular disorders.

• Exogenous proteins might mediate serious reactions– Hypersensitivity reactions.

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Proteins are drugs !

Serving or mimicking an endogenous function:Hormonal therapy (Insulin,)

Exploiting an endogenous reaction:Vaccines

Antagonizing an endogenous function:(infliximab)

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From cells to patients

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Peptide Pros and Cons

Advantages:High Activity, High Specifity, Little unspecific binding to molecular structure other that desired target, Minimization of drug-drug interactions, Less accumulation in tissues, Lower toxicity, Often very potent, Biological diversity

DisadvantagesLow oral bioavailability, injection required, Less stable, Difficult delivery and challenge to transport across membranes, Challenging and costly synthesis, Solubility challenges, Risk of immunogenic effects, Cleared from body quickly

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Origin of peptide products

• Synthetic peptides

• Naturally-derived peptides

• Natural, non-blood derived proteins

• Natural, blood derived proteins

• Recombinant proteins

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Peptide Pharmaceuticals

• Annual market value: $ 35 Bln

• Aprox. 40 marketed peptides worldwide

• 270 in clinical phase

• 400 in preclinical phase

• Growth rate double the rate all APIs(Estimated : 10%)

• Expanding interest in peptides for drug discovery

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Protein Therapeutics

• Market size: 60 bln• Growth rate: 13%

• Aprox. 130 marketed protein therapeutics worldwide

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Major Brands > $ 1 Mln

• Procrit (Johnson & Johnson) – epoetin alpha, treatment of anemia

• Epogen (Amgen)- Epoetin , increase of red blood cells

• Rituxan (Genentech)- Rituximab, treatment of rheumatoid arthritis

• Enbrel (Amgen)- Etanercept, treatment of rheumatoid arthritis

• Remicade (Schering Plough) – infliximab, anti-inflammatory

• Herceptin (Chugai)- Trastuzumab – breast cancer treatment

• Humalog ( Eli Lilly)- Insulin - Diabetes

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Major Brands > $ 1 Mln

• Procrit > $2bln $35/ml

• Epogen $37/ml

• Rituxan $70/ml

• Enbrel $160/vial

• Remicade $700/vial

• Herceptin $1200/vial

• Humalog $ 100/vial

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Iran Sales 4 month

• Procrit > $2bln $35/ml

• Epogen $37/ml

• Rituxan $70/ml

• Enbrel $160/vial 1875 vials / 920,000 Rials

• Remicade $700/vial 659 vials / 6,500,000 Rials

• Herceptin $1200/vial 499vials / 8,000,000 Rials

• Humalog $ 100/vial

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Cost-effectiveness

• Follitorpin Urine collection/Recombinant

• Price

• Batch to batch consistency• Novel new product• Less risk of contaminations

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Production Costs

• $300-$500 per g for 300-500 g

• $100-$200 per g for 1-2 Kg

• $25-$ per g for 50-100 Kg

• <$10 per g for high ranges

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What is PharmacoEconomics (PE)?

Inputs

Costs

Health Care

Outcomes

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Pharmacoeconomics (PE)

• Compares the costs and consequences (outcomes) of drug therapies and medical interventions

• PE analysis– efficient allocation of limited resources among competing alternative medications and

services

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Costs

• What is cost?

• How is cost different from price?

• Do we know the cost of drugs?

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Costs

• Direct costs: costs to deliver services to patient; both medical and non-medical

• Indirect costs: cost of treatment to patient or society

• Intangible costs: quality of life

Advantages:High Activity, High Specifity,

Little unspecific binding to molecular structure other that desired target, Minimization of drug-drug interactions, Less accumulation in tissues, Lower toxicity, Often very potent, Biological diversity

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Costs can be described in many ways

• Cost / unit (cost/tab, cost/vial)• Cost / treatment• Cost / person• Cost / person / year• Cost / case prevented• Cost / life saved• Cost / DALY (disability-adjusted life year)

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Outcomes

• Both positive and negative outcomes should be addressed• Positive outcomes: drug’s efficacy measure• Negative outcomes: ADR and treatment failure

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Most Active Developments

• Types: Cytokines , Monoclonal Antibodies, Vaccines

• Segments: Oncology, Cardiovascular, Infection

GPCR

STY kinases

Zinc peptidases

Serine proteases

PDE

Other 110 families

Cys proteases

Gated ion-channel Ion channels

Nuclear receptor

P450 enzymes

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The top 10 biotechnology companies

Ranking Company Country 2007 pharma sales ($m)

% change vs 2006

2007 total revenues ($m)

1 (1) Amgen US 14,311.00 3.3 14,771.00 2 (2) Genentech US 9,443.00 23.6 11,724.00 3 (3) Genzyme US 2,833.28 21.8 3,813.52 4 (4) CSL Australia 2,661.61 24.0 2,779.95 5 (5) Biogen Idec US 2,136.82 20.0 3,171.62 6 (6) Daewoong

Pharmaceutical South Korea 522.98 23.2 522.95

7 (7) Biotest Germany 338.57 31.4 447.44 8 (8) Orchid

Pharmaceuticals India 315.22 47.7 315.23

9 (12) Crucell Netherlands 243.40 86.5 279.34 10 (9) CK Life

Sciences Hong Kong 190.73 6.7 268.10

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Challenges

• 80’s : Technological challenges for peptide delivery

• High R&D and marketing costs

• Large scale manufacturing

• Competitive environment

• Formulation of stable product

• Delivery of the product to body

• Overcoming short bioavailability

• Peptide production still maturing

• Conventional pharmaceutical formulations would destroy most proteins and eliminate their activities:– Pharmaceutical manufacturing includes harsh processing steps that would be harmful for proteins e.g. heating, high shear force, granulation,

compression, etc.

1. Short shelf life of protein preparations:• If kept in correct conditions, must not be used after 4 weeks post opining

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Challenges

Chance of commercialization from Phase I = 10-20%Chance of commercialization from phase III = 60-80%

• 90% of drugs entering clinical trials fail to make it to market

• The average cost to bring a new drug to market is estimated at $770 million

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Current FDA Policy for approval of rDNA-derived Products

• FR Notice (51 FR 23309), June 26, 1986• Points to Consider in the Production Testing of New Drugs and

Biologicals Produced by Recombinant DNA Technology (April 10, 1986)– Protein drug substances produced by rDNA technology cannot be assumed to be

the same.– IND and Full NDA (505(b)(1)) required.

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Determining the Degree of Similarity of Proteins

• Past: Limited ability to characterize the identity, structure, activity of the active components

• Scientific advances: sensitive and validated assays• Accumulated agency’s experience in making determinations of the

similarity and sameness of peptides and proteins• FDA published recommendations on comparability/evaluations in 1996.

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Product Comparability Testing

• Analytical Testing

• Bioassays

• Pre-clinical Animal Studies

• Clinical Studies

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Pharmaceutical Equivalence (PE)

• Identical active drug ingredients• Identical amounts of active ingredients• Identical dosage forms• Identical compendia or other applicable standard of identity, strength, quality,

and purity

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The ICH S6 Document

usage of relevant vs. non-relevant species

usage of animal models of disease immunogenicity testing and its

implicationsgenotoxicity testingchronic toxicity testingcarcinogenicity testingpreclinical study design

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Toxicology Testing of Biotech-Derived Agents: ICH-S6

General Principles sufficiently well-characterized products rely on purification processes to remove

impurities/contaminants comparability of test material demonstrated

throughout development conventional approaches to toxicity studies often

NOT appropriate to address unique issues GLP compliance

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We sell benefits

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Feature of Benefit?

Advantages:High Activity, High Specifity, Little unspecific binding to molecular structure other that desired target, Minimization of drug-drug interactions, Less accumulation in tissues, Lower toxicity, Often very potent, Biological diversity

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• Protein pharmaceuticals

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nasoohi.sasan@gmail.com