New psoriasis therapies must demonstrate value

Although psoriasis only affects about 2.2% of the population, it is the most prevalent autoimmune disease in the United States, according to the National Psoriasis Foundation (NPS).

The skin condition causes patches of skin redness and irritation. The most common form of psoriasis is plaque psoriasis, in which patients develop thick, red skin with flaky, silver-white patches called scales. People with psoriasis are at increased risk for other health conditions, such as heart disease, diabetes, heart attack, Crohn’s disease, obesity, high blood pressure and depression. NPS estimates that the total cost of psoriasis in the United States is $11.25 billion because of medical expenses and lost wages.

White

“Price increases for these products have consistently outpaced the Consumer Price Index,” says Kimberly White, senior consultant at Numerof & Associates, a healthcare consulting firm.

The development and introduction of novel therapeutic options for psoriasis has raised managed care’s interest in controlling costs associated with dermatology treatments, says Michael J. Sax, PharmD, president, The Pharmacy Group (TPG).  “These agents can cost between $10,000 and $35,000 per month,” he says.

The most successful treatments are biologics, according to Frost & Sullivan's Transformational Health Vice President of Global Life Sciences Nitin Naik.

“The development pipeline for moderate-to-severe psoriasis therapeutics is competitive, with at least 37 investigational biologic and small-molecule drugs in various stages of development,” according to Naik.

Current biologic options for the treatment of psoriasis are anti-tumor necrosis factor (TNF) agents, interleukin-23 (IL-23) inhibitors, and interleukin 17 inhibitors.

Anti-TNF agents target an inflammation causing substance called TNF (a chemical produced by the immune system that causes inflammation).  Anti-TNF agents control inflammation in the joints, gastrointestinal tract, and skin.

Etanercept (Enbrel, Amgen) is a TNF inhibitor used to treat chronic diseases, including moderate-to-severe plaque psoriasis and rheumatoid arthritis.

Interleukins in the IL-23 and Th17 pathway play a pivotal role in the pathogenesis of psoriasis and have become targets for drug development. These molecules have been linked to the skin inflammation of psoriasis.

IL-17 is a cytokine, which is a protein that controls cells and activates inflammation. People with psoriasis lesions, in particular, have 30 times more IL-17 than people without lesions.  Studies have shown that inhibiting IL-17, or reducing it, can help clear psoriasis.

In January 2015, FDA approved Novartis’ Cosentyx (secukinumab), the first IL-17A inhibitor, to treat adults with moderate-to-severe plaque psoriasis. Cosentyx is administered as an injection under the skin.

Cosentyx, ixekizumab (Eli Lilly), and brodalumab (AstraZeneca and Valeant) all work by interfering with the IL-17 pathway.

Ixekizumab, an IL-17A inhibitor, is in clinical development for the treatment of psoriatic arthritis. Brodalumab is an IL-17 receptor monoclonal antibody in development for patients with moderate to severe plaque psoriasis and psoriatic arthritis. Both are expected to receive approval in 2016.

Sax

“These latest drugs more specifically target molecules in the immune system connected to psoriasis than biologics currently on the market,” Sax says.

IL-23

“Interleukin-23 has been recognized as a major factor in the etiology and pathogenesis of psoriasis, and recent therapeutic development has focused on its inhibition of the inflammatory cytokines,” according to Sax.

Tildrakizumab (Sun Pharma and Merck), an IL-23 inhibitor, is under investigation for moderate to severe chronic plaque psoriasis and is currently in phase 3 clinical trials. It is expected to receive approval in 2017.

“The newer biologics have shown to be more effective than some of the current biologics,” says Sax. “Broadalumab and ixekizumab have met all primary and secondary objectives for their evaluation. Ixekizumab has demonstrated superiority to etanercept in phase 3 studies for the treatment of moderate to severe plaque psoriasis.”

Naik

The market also looks to benefit from two novel oral drugs: Tofacitinib (Xeljanz, Pfizer) and apremilast (Otezla, Celgene), according to Naik.

Xeljanz, a Janus kinase (JAK) inhibitor approved for rheumatoid arthritis (RA) in the United States, was recently turned down by FDA as a treatment of adult patients for moderate to severe chronic plaque psoriasis. Pfizer received a complete response letter from the agency for its supplemental New Drug Application for Xeljanz in mid-October. Pfizer will work with the agency to determine an appropriate path forward to address its comments, including providing additional safety analyses of Xeljanz for the proposed indication.

Otezla, an oral, non-biologic selective inhibitor of phosphodiesterase-4 (PDE-4), is currently approved in patients with moderate to severe plaque psoriasis. The drug offers patients and physicians a distinct efficacy-safety profile, an oral route of administration, and no requirement for laboratory monitoring. In phase 3 clinical trials, Otezla resulted in significant and clinically meaningful improvements in plaque psoriasis. Otezla demonstrated a consistent safety and tolerability profile across clinical trials, with no increased risk of malignancy or serious/opportunistic infection. The product labeling does not require routine laboratory monitoring for patients taking Otezla.

In October, a study presented at the 24^th European Academy of Dermatology and Venereology Congress in Copenhagen, Denmark, showed improvements in Psoriasis Area and Severity Index (PASI) scores and disease-related quality of life were observed at week 16 were maintained at week 52 in patients randomized to Otezla at baseline and in patients who switched from etanercept to Otezla at week 16. An exploratory analysis suggested improvements in itching observed at week 16 were also maintained at week 52 in patients in both groups.

Biosimilar TNF agents

There are also three biosimilar TNF inhibitor agents in phase 3 trials for psoriasis-two biosimilar versions of adalimumab (Humira) and one biosimilar etanercept.

Amgen’s phase 3 study evaluated the efficacy and safety of biosimilar candidate ABP 501 compared with AbbVie’s Humira in patients with moderate-to-severe rheumatoid arthritis and met its primary and key secondary end points. Baxalta and Momenta Pharmaceuticals recently announced a pivotal clinical trial of M923, a biosimilar version of Humira, in treating patients with chronic plaque psoriasis. The trial will compare the safety, efficacy and immunogenicity of M923 with Humira. The companies are targeting first regulatory submission in 2017 and a first commercial launch in 2018.

Sandoz, a Novartis company, announced at the beginning of October that FDA accepted its regulatory submission for a proposed biosimilar etanercept to treat a range of autoimmune diseases including rheumatoid arthritis and psoriasis. 

Managed Healthcare Executive Editorial Advisor David Calabrese, chief pharmacy officer with OptumRx, says that the depth and breadth of the clinical development pipeline for both new molecular entities, as well as biosimilars, is a welcomed phenomena, as increased competition is likely to drive opportunity for therapeutic enhancement and for lower drug costs. 

"Within our organization, we are keeping very close tabs on these development activities in an effort to assist our clients in proactively capitalizing in whatever added value these agents bring to the table,” Calabrese says

Naik says the health economics of new products are also becoming increasingly important in light of the entrenchment of the anti-TNFs. “It will be imperative for new agents to make a strong case for cost effectiveness to gain and maintain formulary access in this era of increasing focus on value-driven healthcare, particularly in the event of approval of biosimilar anti-TNFs.”

White says that while psoriasis drugs in general have been shown to be effective in helping patients manage this autoimmune disease, concern remains about the cost-effectiveness. “Further studies need to be done to demonstrate both the economic and clinical value these products bring to the market-and the rationale for why payers and consumers should pay for them," she says. "Additional data is needed to help understand not only how these products reduce direct costs associated with psoriasis treatment, but also indirect costs, such as comorbidities.”

Tracey Walker is content manager for Managed Healthcare Executive.