Coming down the pipeline

| Beth Orenstein

Despite making great strides in their understanding of psoriatic disease, scientists have yet to find a cure. Those strides, however, have helped researchers develop a number of new treatments for psoriasis and psoriatic arthritis (PsA) that can help effectively manage symptoms.

“The market is getting very, very crowded,” said Dr. Paul Yamauchi, clinical assistant professor of dermatology at the David Geffen School of Medicine at University of California, Los Angeles, and NPF Medical Board member.

That is very good news for those living with psoriasis and PsA because it gives them options, said Dr. Abby Van Voorhees, chair of the NPF Medical Board and chair of dermatology at Eastern Virginia Medical School in Norfolk, Virginia. One treatment may be more effective for one patient than it is for another. Another therapy could stop working for a patient, and yet a newer, similar one might work instead, she said.

Although the only way to determine which treatment is best for you is trial and error, your doctor has a number of options to choose from when it comes to treating your psoriatic disease, said Dr. Christopher Ritchlin, chief of the Allergy, Immunology and Rheumatology Division and the Clinical Immunology Research Center at the University of Rochester in Rochester, New York.

Here’s a look at the psoriatic disease treatments currently in the marketplace that seem to show the most promise, according to the five dermatologists and one rheumatologist interviewed for this article.

Blocking proteins

Biologics are medications manufactured in a laboratory from living cells. Many patients have success with the type of biologic that targets tumor necrosis factor-alpha (TNF-alpha), a protein that stimulates an immune response that results in inflammation. In people with psoriasis and psoriatic arthritis, TNF-alpha is a key player in the inflammatory process that causes skin cells to grow rapidly, leaving plaques and damaging joints.

The U.S. Food and Drug Administration (FDA)-approved TNF-alpha inhibitors for psoriatic disease include Enbrel (etanercept), co-marketed by Amgen and Pfizer in North America, AbbVie’s Humira (adalimumab) and Jannsen’s Remicade (infliximab). Jannsen’s Simponi (golimumab) and another TNF-inhibitor, UCB’s Cimzia (certolizumab pegol), have been FDA approved for the treatment of PsA but not for the treatment of plaque psoriasis.

The recent focus of research has been on blocking proteins that play a role in the inflammatory process that leads to psoriatic disease.

“Think of a Google map of New York City,” said Van Voorhees. “If you want to go from A to Z, you can go east and then south. Or you can go south first and then east. Each is a different pathway that leads you to the same place.”

It’s the same with newer biologics, she said. Each blocks a different pathway (protein), with the goal of stopping the inflammation that damages skin and joints. Interleukin-17 (IL-17) and IL-23 are the pathways receiving the most attention, although IL-17 is more specific for psoriasis, Yamauchi said.

The FDA recently approved two new biologics, Cosentyx (secukinumab) by Novartis and Taltz (ixekizumab) by Eli Lilly, that bind to IL-17 and inhibit the immune response.

“They appear to be dramatically effective in [treating] psoriasis,” said Dr. Mark Lebwohl, former president of the American Academy of Dermatology, chair emeritus of the NPF Medical Board and dermatology professor at the Icahn School of Medicine at Mount Sinai in New York.

In July, an FDA advisory committee recommended that Valeant Pharmaceutical International’s brodalumab, which also binds to IL-17, be approved for adult patients with moderate to severe plaque psoriasis, and the FDA generally follows the advice of its panels, said Dr. Jashin J. Wu, director of dermatology research at Kaiser Permanente Los Angeles Medical Center and NPF Medical Board member. That could mean that patients may soon have a third option for a biologic that targets IL-17.

Most patients on IL-17 biologic treatment require injections every two to four weeks. Research shows biologics are generally safe and do not often result in serious side effects. However, patients should be carefully monitored, as the medications suppress the immune system, making them more susceptible to infections, Wu said.

Also in the pipeline are several biologics that target IL-23 for the treatment of moderate to severe psoriasis, including Sun Pharmaceutical and Merck’s tildrakizumab and guselkumab. Yet another is risankizumab; in March, AbbVie and Boehringer Ingelheim announced a global collaboration to develop and commercialize that treatment.

“The maintenance dosing of risankizumab will likely be every 12 weeks, which would be an IL-17,” Wu said.

Stelara (ustekinumab) by Janssen is another biologic that has been on the market for a number of years and is used to treat plaque psoriasis and psoriatic arthritis.

“It appears to be quite safe,” Lebowohl said.

Stelara blocks a small part of the immune system, IL-12 and IL-23.

“There are people born with defects in the molecule that Stelara blocks, and they may be susceptible to mycobacterial infections such as tuberculosis (TB) and salmonella infections,” Lebwohl said. “We have not seen salmonella in patients on Stelara. And it’s easy to monitor patients for TB. If a TB test comes back positive, we simply treat it.”

The maintenance dosing is one shot every 12 weeks, so it may be better for patients who are unable to get shots more frequently, Wu said. It is also one of the few biologics that is weight-based, so heavier patients might have a better response with the higher dose of Stelara, compared to the one-size-fits-all dosing of other biologics, according to Wu.

Oral medications

On the market for about two years, Celgene’s Otezla (apremilast) has proven to be an effective and well-tolerated option for the management of psoriasis and PsA in adults, Lebwohl said.

The advantage to Otezla is that it comes in pill form, “and a lot of patients prefer taking pills to injections,” Yamauchi said. It targets an enzyme known as phosphodiesterase 4 (PDE4) to better regulate inflammation signaling within cells. Otezla can be taken in combination with other treatments, the dermatologists said.

Pfizer is investigating another oral medication for psoriatic arthritis, tofacitinib, and phase III trials are under way. Tofacitinib targets yet another enzyme that, if blocked, could prohibit the inflammatory process that leads to skin and joint damage, Lebwohl said. Tofacitinib has already been approved to treat rheumatoid arthritis, and goes by the brand name Xeljanz.

Topical treatments

In the past decade, new topicals have become available as well. Topicals may be used with oral drugs or biologics and are available over the counter and by prescription. Prescription topicals include strong steroids to reduce inflammation and redness.

Some of the newer topicals, according to Dr. Linda Stein Gold, director of dermatology clinical research and division head of dermatology at the Henry Ford Hospital in Detroit, include:

  • Enstilar, an aerosol foam made by LEO Pharma, is a combination of two medications: calcipotriene, a vitamin D-based treatment, and betamethasone dipropionate, a topical steroid. The FDA approved Enstilar for plaque psoriasis in October 2015.
  • Sernivo, a spray made by Promius Pharma, contains betamethasone dipropionate. The FDA approved Sernivo for plaque psoriasis in adults in February 2016.

“The medication field for psoriatic disease has grown considerably in the last few years and, from my perspective, that growth is great,” Van Voorhees said. “There are so many choices to manage the individual patient, and we need them all. It’s very helpful to have so many choices.”

What about biosimilars?

In April 2016, the FDA approved Pfizer’s Inflectra, a biosimilar for treatment of psoriasis and psoriatic arthritis that is similar biologically to Remicade (infliximab). As of press time, Pfizer announced that Inflectra may come to market as early as November 2016.

Two more biosimilars used in the treatment of psoriatic disease – for Enbrel (etanercept) and Humira (adalimumab) – have since received FDA approval.

Doctors who treat psoriatic disease are looking forward to having more biosimilars available because they hope the treatments will be less expensive and function as well as the biologic to which they are similar, said Van Voorhees. However, “we haven’t had any experience using them, so we don’t know whether this will truly be of benefit to our patients,” she said.

To win FDA approval, biosimilars must be highly similar to a biologic product already on the market and show no clinically meaningful differences from the reference biologic.

NPF’s government relations team is currently working to pass legislation across the country that would ensure that the decision to take a biosimilar stays between the doctor and patient. To that end, NPF has adopted a statement on biosimilars that recommends, among other things, that the following thresholds be met for biosimilar substitution to occur.

  • The FDA has designated that the biosimilar is interchangeable with the biologic that had been prescribed.
  • The pharmacist notifies the prescriber of the substitution electronically or in writing within 48 hours.
  • The patient is informed and educated about the biosimilar substitution at the time of sale.

 

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