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Guselkumab: A Step Ahead in the Battle against Moderate-to-Severe Plaque Psoriasis

The promise of selective IL-23 inhibitors in treating inflammatory diseases such as Psoriasis was borne out in mid-July 2017, when Janssen’s Tremfya® (guselkumab), a selective IL-23 inhibitor, was approved for the treatment of moderate to severe plaque psoriasis patients who are candidates for systemic therapy or phototherapy. Janssen’s decision to use a priority review voucher for submission of the biologics license application was fruitful and led to guselkumab’s approval four months before its estimated PDUFA date of November 2017.

PharmGPS® distinguished guselkumab from other emerging drugs, months in advance, based on Phase II data on efficacy, safety and dosing regimen, as a front runner for treating patients with moderate to severe plaque psoriasis. Guselkumab represents a significant landmark for the plaque psoriasis patient community, given its demonstrable skin clearance data in Phase II and Phase III trials. In addition, Guselkumab has outscored Humira® and Stelara® in head to head trials (p<0.001 for all comparisons of guselkumab with placebo and Humira®).

PharmGPS® analysis of IL-17 and IL-23 as targets in many autoimmune diseases revealed advantages of targeting IL-23 over IL-17. In psoriasis, IL-23 is overproduced by dendritic cells and keratinocytes and stimulates Th17 cells within the dermis to produce IL-17A and IL-22. Though the discovery of the IL-23-Th17 immune pathway is a decade old, researchers have only recently realized the advantages in the selective blockade of the IL23. Acting upstream in the IL-23/IL-17 cytokine pathway is likely to reduce the expression of multiple pro-inflammatory cytokines acting on keratinocytes including IL-17F, IL-21, and IL-22, in addition to IL-17A. Also, safety data thus far suggest that these drugs might be devoid of some adverse effects of IL-17A blockade that seem to be class related, such as mucocutaneous Candida infections or triggering/worsening of inflammatory bowel disease.

Currently, four companies are developing selective IL-23 inhibitors: Janssen, Sun Pharmaceuticals, Boehringer Ingelheim GmbH/Abbvie and Eli Lilly. Janssen achieved a significant milestone by succeeding in the development of an IL-23 inhibitor in the highly competitive landscape of plaque psoriasis. When compared to Stelara® and Humira®, guselkumab administered at the dose of 100 mg subcutaneously every eight weeks demonstrated significant efficacy in patients with moderate to severe plaque psoriasis. Guselkumab has been successful in achieving at least 90% clearer skin, and more than 80% patients experienced clear or almost cleared skin. Improvements were also observed on the scalp and in plaque psoriasis symptoms such as itching, burning, stinging, pain, and skin tightness. Guselkumab further delivered significant improvement for psoriasis patients who had an inadequate response to J&J's Stelara® (ustekinumab) as demonstrated by the NAVIGATE study. The clinical trial results published to date are summarized below:

The blockbuster potential of guselkumab may further be strengthened when results of the ongoing Phase III head-to-head study comparing it with Cosentyx® (secukinumab) in the treatment of moderate to severe plaque psoriasis are published.

PharmGPS® has also evaluated other pipeline IL-23 inhibitors in clinical development: risankizumab (Boehringer Ingelheim/Abbvie) and tildrakizumab (Sun Pharma), of which risankizumab demonstrated promising efficacy results. Apart from this, Eli Lilly’s mirikizumab is in Phase I development.

Furthermore, the family of IL-17 inhibitors (Cosentyx®, Taltz® and Siliq®) have similar efficacy data, but they have safety concerns and warnings on their labels. Tremfya® has performed extremely well on efficacy (PASI 50: 60%; patients with sPGA of clear disease: 78.6%) and is comparatively safer. Having achieved excellent efficacy, it is likely to replace Stelara® as the standard of care in the near future.

PharmGPS® currently forecasts Tremfya® sales in G-7 at $53M in 2018, growing to $165M in 2019 and $750M in 2021. Tremfya® is expected to attain a peak market share of 6.7%, which corresponds to the sales of $1.1B by 2024. JNJ had previously identified the compound as one of its 10 new drugs that could reach $1B+ peak sales

About Psoriasis:

Psoriasis is a lifelong challenge to live with and nearly 125 million people suffer worldwide from this disease which is characterized by raised, inflamed, scaly, red lesions, or plaques that can cause itching and pain. An estimated 80% to 90% of people suffer from plaque psoriasis, of which approximately 20% have moderate-to-severe disease. Janssen’s Stelara® (IL-12/IL-23 inhibitor) is considered as the current standard of care for moderate to severe psoriasis patients.

The last decade has seen tremendous success of targeted therapies in the psoriasis market with the approval of Stelara®, IL-12/IL-23 inhibitor (Janssen, September 2009); Enstilar®, VDR/GR agonist (Leo Pharmaceuticals, October 2015) and Otezla®, PDE4 inhibitor (Celgene, September 2014). This has been followed by drugs which specifically target the pro-inflammatory cytokine, interleukin 17 (IL-17) such as Taltz® (Eli Lilly, March 2016); Cosentyx® (Novartis, January 2015) and more recently, Siliq® (Valeant Pharmaceuticals, February 2017) and this class of drugs has already started dominating the current market.

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