Wednesday 17th February, 2021
Approaches to Determining Safety & Tolerability in Phase 1/2 Drug Development
09:00 – 12:00
One of the main costs in drug development is establishing safety for a new drug. Identification of potential safety issues early in clinical testing and optimisation of safety testing throughout clinical development are critical for efficient and cost-effective drug development, allowing for more productive agency discussions of requirements and de-risking late clinical development.
In dermatological drug development there are different scenarios for safety testing dependent on the route of administration: systemic, transdermal, or locally applied with local effects. For systemically applied drugs and biologics, evaluation of drug safety and risks is generally similar to other therapeutic areas. However, for topical (semi-solid, transdermal delivery) or intradermal application, cutaneous adverse effects must be considered as well as possible systemic effects. Especially in the case of highly potent or narrow-therapeutic index drugs, a better understanding of API distribution in the skin and skin PK/ PD can allow better modelling to identify potential safety issues very early in development.
In a question-based drug development plan, decision points that are relevant to the development of knowledge about both safety and efficacy drive the development path to provide a better reflection of true risks and benefits. These questions include assessment of all clinical effects including the therapeutic window, skin pharmacokinetics and pharmacodynamics including possible skin depot effects and thus resulting cutaneous adverse effects, formulation based effects on the skin, possible transference issues for topically applied drugs, and population-based differences in risk/benefit.
In this workshop we will highlight how skin PK and PD may not only contribute to a de-risking of topical and intradermal drugs but may also allow to de-risk drug development in terms of evaluation of safety throughout clinical development, particularly on identifying systemic and local safety issues early in clinical development.
Topics will include:
- In-vitro PK for formulation development
- In-vivo skin PK for lead compound selection
- Proof-of-Mechanism of API
- Applied dose to drug response
- Topical formulation implications on cutaneous safety
- Target-population differences in cutaneous effects
- Cutaneous safety: Designs and placement during development of irritation and sensitisation studies
- Photosafety (phototoxicity and photosensitisation)
- Real and perceived sensitive skin
- More efficient development by consistent reporting of
cutaneous adverse effects throughout development
Dermatology Drug Development
Institute for Biomedicine & Health Sciences
Research Director, Dermatology
Center for Human Drug Research
JAK Inhibitors Changing the Landscape of Dermatologic Therapy
1:00PM – 3:00PM
The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway is a universal intracellular signaling network.
Selective JAK-inhibitors have anti-inflammatory properties and have been approved in many countries for the treatment of rheumatoid arthritis and myelofibrosis or polycythemia vera.
Thus, JAK1 inhibition is a promising approach to inflammatory dermatologic diseases,
The efficacy and safety of JAK-inhibitors in skin diseases, such as psoriasis, alopecia areata, atopic dermatitis and vitiligo remains an area of hot discussion and analysis. Mostly, JAK-inhibitors are used orally. However, there are also now studies showing efficacy of topical administration of this group of drugs in psoriasis and vitiligo.
Currently, there are no JAK inhibitors approved by the U.S. Food and Drug Administration (FDA) for a dermatologic condition. However, predictions state the first approval within the next one to two years.
In this workshop, Fiona and Yiumo will introduce the JAK family and their function in dermatology.
- Assess disease background, pathogenesis and unmet medical need, followed by an analysis on current oral JAK inhibitor and topical JAK inhibitors
- Gain knowledge of potential target therapies in treatment of both Atopic Dermatitis and Vitiligo, alonsg with, compound efficacy and relevant clinical trial results
- Learn why topical JAK does not work in Alopecia Areata, and how oral JAK inhibitors can work
Key Highlights include:
- Benefits of JAK inhibitor versus pan JAK inhibitors
- JAK inhibitor safety profile and concerns. How to manage it?
- Systemic JAK inhibitors versus topical JAK inhibitors
- Study JAK deficiency in humans and mice
- A brief overview of Hidradenitis Suppurativa, Psoriasis Vulgaris, Lichen Planopilaris, and Pyoderma Gangrenosum
Director, Clinical Science
Yiumo Michael Chan
Senior Director, Head of Medical Research
TWi Biotechnology, Inc