Psoriasis

This is the public user homepage for the Psoriasis Therapeutic Area.  The Psoriasis homepage includes links to relevant resources, daily and archived Psoriasis news of interest, mini-reviews of Hot Topics, and a continuously updated Pipeline Table in addition to the STEPh REPORT for Psoriasis.

The STEPh REPORT for Psoriasis reviews compounds and development programs currently under study from preclinical through NDA submission.  Information is reviewed in multiple formats:

  • mechanism of action
  • phase of development
  • projected year of approval

In addition, each compound has its own monograph that expands on the clinical efficacy and safety information reported during clinical trials.  Where available, links are provided to abstracts of relevant information such as published literature, SEC filings, and press releases.  The Psoriasis STEPh REPORT is kept current as new information becomes available (e.g., new reports are uploaded every other month).  After downloading the STEPh REPORT, you can select the bookmark function from the PDF file for easy maneurverability through the document.

The Psoriasis homepage also includes links to relevant resources, daily and archived MS news of interest, mini-reviews of Hot Topics, and a continuously updated Pipeline Table.

Access to the full Psoriasis STEPh REPORT as well as the other information in this section of the web site is available by subscription.  Please feel free to contact us for more information about becoming an active subscriber to this and other services offered by STEPh Inc.

Table of Contents

TABLE OF CONTENTS

TOPLINE SUMMARY

Treatment

Topical Agents

Phototherapy and Oral Systemic Agents

Biologics

Measurement of Treatment Success

Drug Development Pipeline

Topical Agents

Oral Agents

Biologics

References

 

OVERVIEW OF TOPICAL AGENTS IN DEVELOPMENT FOR PSORIASIS

Place in Therapy

Topical Steroids

Table 1.  Efficacy of Different Classes of Topical Corticosteroids for Psoriasis

Vitamin D Analogues

Combination Corticosteroid/Vitamin D Formulations

Breadth of Development Programs

Table 2.  Topical Agents in Development for Psoriasis

Table 3.  Earliest Potential Year of Approval for Topical Agents

References

 

OVERVIEW OF BIOLOGICS IN DEVELOPMENT FOR PSORIASIS

Place in Therapy

Table 1.  Biologics for Treatment of Psoriasis and Psoriatic Arthritis

Breadth of Development Programs

Table 2.  Injectable Agents in Development for Psoriasis

Table 3.  Earliest Potential Year of Approval for Injectable Agents

References

 

OVERVIEW OF ORAL AGENTS IN DEVELOPMENT FOR PSORIASIS

Place in Therapy

Breadth of Development Programs

Table 1.  Oral Agents in Development for Psoriasis

Table 2.  Earliest Potential Year of Approval

References

 

OVERVIEW OF AGENTS IN DEVELOPMENT FOR TREATMENT OF PSORIATIC ARTHRITIS

Background Information

Breadth of Development Programs

Table 1.  Agents Currently Under Study for Psoriatic Arthritis

Table 2.  Earliest Potential Year of Approval for Agents Under Study for Psoriatic Arthritis

References

 

COMPOUNDS AVAILABLE FOR LICENSING

 

INDIVIDUAL DRUG MONOGRAPHS

Table 1.  Phase of Development for Psoriasis Compounds

Table 2.  Earliest Possible Approval Date for Psoriasis Compounds in Development

Individual Drug Monographs (alphabetical order)

 

 

TOPLINE SUMMARY

 

Background Information

Psoriasis is a chronic inflammatory disease that affects approximately 1% to 4.7% of the world’s population.  Although psoriasis can manifest at any age, it is most common in two age groups—20 to 30 years, and 50 to 60 years.  Approximately 80% of patients have mild to moderate disease with severity defined by extent of body surface area involvement (<5% = mild, >5% but <10% = moderate, and >10% = severe), and involvement of specific areas of the body (e.g., face, feet, genitalia).  Psoriasis has multiple clinical variants (i.e., plaque, guttate, inverse, pustular, erythrodermic, nail, psoriatic) with plaque psoriasis (characterized by well-demarcated, scaly, pink to red plaques) accounting for more than 80% of cases.

Burden of disease is great with direct medical costs in excess of $1 billion annually.  Quality of life is significantly impaired and psoriasis patients routinely experience interference in activities of daily living and diminished personal well-being.  Co-morbid conditions include metabolic syndrome and cardiovascular disease including an increased risk of myocardial infarction and cardiovascular death.

Genetic and environmental factors (sunburn, infection, drugs) are involved in the disease process.  The hallmark of disease is keratinocyte proliferation, which is mediated by a complex series of interactions that involves several immune cell types including T cells, neutrophils, dendritic cells and macrophages.  Among the various cytokines implicated in the pathogenesis of psoriasis are tumor necrosis factor alpha (TNF-α), IL-12 (induces Th-1 differentiation and increases production of TNF-α), and IL-23 (stimulates Th-17 and synthesis of IL-17 and IL-22).

Treatment

Therapeutic options for the treatment of psoriasis consist of topical agents, phototherapy, systemic oral agents, and biologics with treatment selection influenced by the severity of disease and location.

Topical Agents

The majority of patients with psoriasis have mild to moderate disease, which can be adequately managed with topical therapy (i.e., corticosteroids, vitamin D analogues) administered alone or in combination and either intermittently or longer-term.  Topical corticosteroids are the mainstay of treatment for those with limited disease.  These compounds differ with respect to strength/potency and available formulations.  In general, the choice of corticosteroid is influenced by the severity of disease, plaque location, and age of patient.  Whereas mid and higher potency formulations are generally recommended as initial therapy for most patients, areas of the body with thin skin such as the face should be treated with lower potency agents and areas with thick, chronic plaques should be treated with the highest potency compounds.  Efficacy rates reported in the literature vary widely even among agents within the same potency class and have ranged from 41%-92%.  In these studies, treatment was usually of short duration (i.e., between 2 and 4 weeks).  Treatment is usually well tolerated with local side effects (e.g., skin atropy, acne, folliculitis, exacerbation of existing dermatoses) of limited importance.  Reduced therapeutic effects can occur over time and more serious systemic side effects (e.g., HPA axis suppression, Cushing’s syndrome) are possibe when potent and superpotent corticosteroids are applied over a large surface area for prolonged periods of time.  Thus, superpotent agents should be limited to short-term use (up to 4 weeks and no more than 50 g/week).  Although topical monotherapy of more severe disease is of limited benefit, topical agents can further improve outcomes when administered in combination with light therapy, traditional systemic agents, or biologic agents in patients with moderate to severe disease.

Several vitamin D analogues are available for use (e.g., calcipotriene, calcitriol) with calcipotriene first approved in the US in 1994.  Calcipotriene has been shown to improve signs and symptoms in approximately 60%-70% of patients with maximal effects observed at weeks 6 to 8.  Cutaneous irritation is a common side effect to calcipotriene therapy.  Calcitriol has similar efficacy to calcipotriene but is less irritating especially on the face and intertriginous zones.  It is administered as an ointment twice-daily for treatment of mild-moderate disease in patients aged 18 and older.

Phototherapy and Oral Systemic Agents

Targeted phototherapy and oral systemic agents (e.g., methotrexate, cyclosporine, acitretin) are generally reserved for patients with moderate to severe disease.  There are multiple types of phototherapy (ultraviolet A + psoralen, ultraviolet B) and dosing is required several times per week.  Phototherapy is effective in the majority of eligible candidates, is cost-effective, and is devoid of systemic toxicities and immunosuppressive properties of systemic treatments.  It is particularly useful in the treatment of pregnant women with mild to moderate disese.  Side effects to treatment include nausea, itching, redness of the skin, photoaging and long-term risk of skin cancer.   Oral systemic agents are relatively inexpensive, fast acting, and recommended for select patients use prior to biologic therapies.  Drawbacks to therapy include safety concerns such as immunosuppression.

Biologics 

An increased awareness of the mechanisms responsible for the immunopathogenesis of psoriasis has led to the development of multiple biologic agents that target specific cytokines responsible for plaque formation.  The most well characterized group of biologics are the tumor necrosis factor α (TNF-α) antagonists.  As a class, biologics are indicated for the treatment of chronic moderate to severe plaque psoriasis in patients who are candidates for phototherapy or systemic therapy, and when other systemic therapies are medically less appropriate.  Some of these agents are also indicated for psoriatic arthritis in addition to ankylosing spondylitis, Crohn’s disease, and rheumatoid arthritis.  Major drawbacks to biologic therapy include high cost of therapy, need for SC or IV administration, and potential for serious infections and malignancies.  Thus, these drugs should only be administered to patients who will be closely monitored and regularly followed by a physician.  There is one T-cell receptor vaccine (ZORCELL) in development for use in combination with other treatment (e.g., methotrexate).

Measurement of Treatment Success

The most commonly used assessment tool in psoriasis clinical trials is the Psoriasis Activity and Severity Index (PASI), which is a composite score that takes into consideration both the extent of body surface area affected and the nature and severity of psoriatic changes within the affected regions (induration, erythema and scaling).  The PASI 75 is defined as 75% reduction in PASI compared with baseline and is a standard primary outcome measure.

The Static Physician Global Assessment (sPGA) is used to evaluate the involvement of body surface area, induration, scaling and erythema and grades the patient’s overall psoriasis relative to baseline on a 6-category scale ranging from “5 = severe” to “0 = none”.

The American College of Rheumatology Criteria (ACR) is used to evaluate clinical response in patients with psoriatic arthritis.  The ACR clinical response critieria are defined as percentage reduction [20% (ACR20), 50% (ACR50), and 70% (ACR70)] in tender and swollen joint counts, and in patient and physician global assessments, pain, disability and an acute phase reactant.

Drug Development Pipeline

There are ~65 agents from corporate sponsors currently in various stages of development  for treatment of psoriasis.  Approximately half of the development programs are in phase II with the balance nearly equally split between phase III and phase I/preclinical.  Four agents (i.e., apremilast, FP187 [Germany], secukinumab, tofacitinib) have the potential to gain licensure in 2014 and six others (brodalumab, ixekizumab, LEO 90100, 000-0051, LAS41004 [Europe], M5180) in 2015.

Topical Agents

There are approximately 25 topical agents, across a wide array of pharmacological activity,   under study for treatment of psoriasis with the majority in phase II development.

  • Novel mechanisms of action relative to corticosteroid and vitamin D products currently marketed      include inhibition of PDE4 inhibition, integrin, and kinases.
  • Given the current development status of this group, new drug approvals are unlikely prior to 2015 at the earliest with the majority projected for the latter part of this decade assuming positive outcomes from late phase trials.

Nearly all of these agents are under study for mild to moderate disease but limited outcome data are available to determine if compounds with novel mechanisms of action will provide added benefit over existing topical therapies.

Oral Agents

There is a definite need for novel, orally available small molecules that are better tolerated than current oral therapies and with efficacy profiles suitable for use in patients with moderate to severe disease.  There are approximately 20 oral agents in development for treatment of psoriasis with the majority currently undergoing phase II testing.  Three agents have the potential to gain licensure in 2014.  Highlighting this list are JAK and PDE4 inhibitors, and fumarate esters similar to Fumaderm but with potential for better tolerability.

  • Initial efficacy data show PASI 75 results ranging from ~40% for apremilast and 50% for ponesimod.  Preliminary results for tofacitinib from an active comparator study demonstrated similar efficacy to etanercept when dosed at 10 mg BID.
  • Side effect profiles differ for each class of agent with PDE4 inhibitors being well tolerated and JAK inhibitors showing similar effects to biologics.
  • As a group, new oral agents that are well tolerated and can demonstrate significant      efficacy in patients with moderate to severe psoriasis (although likely less than for biologics) have the potential to gain significance acceptance in the marketplace.  Also driving this cause would be lower patient costs relative to biologics and greater patient acceptance over injectable therapies.

Biologics

There are nearly 20 injectable agents in development for treatment of psoriasis, dominated by monoclonal antibodies that are aimed at multiple mediators of inflammation.  Recent attention has been directed at biologics that target IL-12, IL-17, and IL-23, and three of these agents (brodalumab, secukinumab, ixekizumab, all administered SC) have the potential to gain licensure in the US within the next 2 years.  Preliminary phase II data for these agents indicate PASI 75 results of ~80% for each.  Initial phase III FIXTURE Study] data for secukinumab showed superiority over etanercept.

  • Preclinical data indicate that agents that solely target IL-23 (and not IL-12) may have fewer safety issues than agents that target both cytokines.
  •  It remains to be determined how the efficacy and safety profiles of these newer biologics will compare with those of already marketed agents.

REFERENCES

American Academy Dermatology Work Group, Menter A, Korman NJ, Elmets CA, et al.  Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions.  J Am Acad Dermatol 2011;65:37-174.  [  http://www.aad.org/education-and-quality-care/clinical-guidelines/current-and-upcoming-guidelines ; scroll down to Section 6, July 201].

American Academy Dermatology Work Group, Gotlieb A, Korman NJ, Gordon KB, et al.  Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: Overview and guidelines of care for treatment with emphasis on the biologics.  J Am Acad Dermatol 2008;58:851-864. [ http://www.aad.org/education-and-quality-care/clinical-guidelines/current-and-upcoming-guidelines ; scroll down to Section 2, May 2008].

Armstrong EJ, et al.  Psoriasis and major adverse cardiovascular events: A systemic review and meta-analysis of observational studies.  J Am Heart Assoc 2013;2:e000062. http://jaha.ahajournals.org/content/2/2/e000062.long .

Devaux S, Castela A, Archier E, et al.  Topical vitamin D analogues alone or in association with topical steroids for psoriasis: a systemic review.  J Eur Acad Dermatol Venereol 2012;26 (Suppl. 3):52-60.  http://www.ncbi.nlm.nih.gov/pubmed/22512681 .

Hendriks AG, Keijsers RR, de Jong EM, Seyger MM, van de Kerkhof PC.  Efficacy and safety of combinations of first-line topical treatments in chronic plaque psoriasis: a systematic literature review.  J Eur Acad Dermatol Venereol 2012; doi: 10.1111/jdv.12058. http://www.ncbi.nlm.nih.gov/pubmed/?term=Efficacy+and+safety+of+combinations+of+first-line+topical+treatments+in+chronic+plaque+psoriasis%3A+a+systematic+literature+review. .

Laws PM, Young HS.  Update of the management of chronic psoriasis: new approaches and emerging treatment options.  Clin Cosmet Investig Dermatol 2010;3:25-37.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047953/  .

Mattei PL, Corey KC, Kimabll AB.  Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI): the correlation between disease severity and psychological burden in patients treated with biological therapies.  J Eur Acad Dermatol Venereol 2013; doi: 10.1111/jdv.12106.  http://www.ncbi.nlm.nih.gov/pubmed/?term=Mattei+psoriasis+area+severity+index+(PASI)+and+the+dermatology .

Menter A, Korman NJ, Elmets CA, et al.  Guidelines of care for the management of psoriasis and psoriatic arthritis: section 3.  Guidelines of care for the management and treatment of psoriasis with topical therapies.  J Am Acad Dermatol 2009;60:643-659. [ http://www.aad.org/education-and-quality-care/clinical-guidelines/current-and-upcoming-guidelines ; scroll down to Section 3, April 2009].

Rustin MH.  Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data.  Br J Dermatol 2012;167 (Suppl 3):3-11.  http://www.ncbi.nlm.nih.gov/pubmed/23082810 .

Samarasekera EJ, Sawyer L, Wonderling D, Tucker R, Smith CH.  Topical therapies for the treatment of plaque psoriasis: systemic review and network meta-analyses.  Br J Dermatol 2013; doi: 10.1111/bjd.12276. http://www.ncbi.nlm.nih.gov/pubmed/23413913 .