Anacor Pharmaceuticals' AN2728 - novel topical PDE4 inhibitor for atopic dermatitis

  • ID: 2849595
  • Report
  • Region: Global
  • 45 Pages
  • LifeTech Research
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Anacor's AN2728 is a boron-containing topically administered phosphodiesterase 4 (PDE4) inhibitor that suppresses the release of TNF-alpha, IL-12 and other inflammatory cytokines. The compound is entering phase III trials in atopic dermatitis and has also been extensively tested in psoriasis. Atopic dermatitis is a common inflammatory skin condition that occurs predominantly in children.

Topical steroids are the mainstay of therapy, but have a number of side effects that limit their use. Topical calcineurin inhibitors are the main non-steroidal therapeutic alternative, but have an associated cancer risk that limits their appeal. Thus, there is a need for a new non-steroidal therapy that provides efficacy without the toxicity issues of topical steroids and calcineurin inhibitors.

Pre-clinical data show clear anti-inflammatory activity. Initial small clinical studies have shown that AN2728 is active in atopic dermatitis as well as in psoriasis. Ultimately, drug approvals in this space require robust data not only for efficacy but also for safety. Given that atopic dermatitis is not a life-threatening disease and that it primarily affects children, the bar for safety is very high. In this report, we review the science, the rationale for AN2728's development, the strength of the early clinical data, general safety concerns for PDE4 inhibitors and for the boron element, competition and the commercial landscape for the product.
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FEATURED COMPANIES

  • Almirall
  • Celgene
  • Eisai
  • HanAll Biopharma
  • Maruho
  • Otsuka
  • MORE
Introduction 3

Atopic dermatitis 3

AN2728 7

Preclinical and early phase data—rationale for use 7

Proof of concept 8

Preclinical safety 8

Clinical trials in atopic dermatitis 10

AD-202 trial 11

AD-203 trial 12

AD-204 trial 13

Ancillary studies 15

Phase III plans 15

AN2728 in psoriasis 15

Microplaque phase I trials 15

Phase II bilateral studies 16

Parallel vehicle controlled study 17

Additional studies expand the safety database. 18

Low absorption provides a very wide safety window 18

Clinical and regulatory Discussion 19

PDE4 inhibition as a drug target 19

The rationale for developing a topical PDE4 inhibitor 19

AN2728 seems to be active in atopic dermatitis, but the magnitude of benefit is unclear 20

Bilateral vs. parallel results in psoriasis trials are informative 21

Safety should be the main regulatory bar 21

There is substantial knowledge about the PDE4 inhibitor class 22

Gastrointestinal toxicities are characteristic of systemic PDE4 inhibitors 22

Is carcinogenicity a concern with PDE4 inhibitors? 23

The Elidel and Protopic precedent should trigger scrutiny for malignancy signal 23

What do we know about AN2728's carcinogenicity risk? 24

Does boron add any unique safety concerns for AN2728? 24

How does AN2729 compare with other non-steroidal topical agents? 25

The challenges of measuring outcomes in atopic dermatitis trials 26

The IGA scale is most commonly used for FDA submissions 27

What does this mean for AN2728? 27

Elidel's regulatory pathway provides relevant perspective 28

MARKET OPPORTUNITY 30

COMPETITION 32

SUMMARY OPINION 37
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- Novartis
- Otsuka
- PreCision Dermatology
- Regeneron
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