USA: FDA Approves First Once-Daily Oral Plaque Psoriasis Drug

From verywellhealth.com

Key Takeaways

• Regulators approved an oral once-daily drug, called Sotyktu (ducravacitinib) for treating moderate to severe plaque psoriasis.
• Clinical trials showed that the drug is more effective and better tolerated than the twice-daily oral psoriasis drug, Otezla (apremilast).
• An oral medication may be easier for patients to take than injectable biologics.
• 

  Lara Antal / Verywell

Last week, the FDA approved Sotyktu (deucravacitinib), a once-daily oral pill by Bristol Myers Squibb for people with moderate to severe plaque psoriasis—a chronic, systemic, immune-mediated disease.

The medication is meant to treat adults who have plaque psoriasis severe enough to make them candidates for systemic therapy and phototherapy.

Many of the drugs that are available to treat severe cases of plaque psoriasis are biologics that are injected or administered intravenously. These can be expensive and often require patients to routinely visit a provider to be treated and monitored. Even oral immunosuppressant options can increase the risk of infection and other undesirable side effects.

Deucravacitinib is the first oral treatment for plaque psoriasis that can be taken just once daily and the first oral medication approved for the disease in a decade. In clinical trials, the drug appeared to be more effective than the popular psoriasis drug, Otezla (apremilast).

More than 7.5 million U.S. adults live with psoriasis, according to the National Psoriasis Foundation. As many as 90% of those patients have plaque psoriasis, characterized by raised patches of inflamed and discoloured skin, and nearly a quarter of those have moderate to severe cases.

Unlike existing treatment for this population, deucravacitinib doesn’t require laboratory follow-up and seems to be well-tolerated, said April Armstrong, MD, MPH, professor of dermatology and associate dean of clinical research at the University of Southern California, who led the clinical trials.

“This is a breakthrough medication and, in my opinion, this drug will be the leading oral agent for our patients with psoriasis because of its robust efficacy and good safety profile,” Armstrong told Verywell. “I'm very excited to talk to my patients about this drug.”

Clinical Trials Show Significant Plaque Improvement

The FDA approved the drug based on two clinical trials, which compared deucravacitinib to apremilast in nearly 1,700 adults with a mean age of 46 years.

These participants all had moderate to severe plaque psoriasis. On average, they experienced psoriasis for 17 years on a quarter of their bodies. More than a fifth had clinically severe psoriasis and nearly 40% had used biological therapies to control their condition.

One group took a 6-milligram tablet of deucravacitinib once per day. Other participants took 30 milligrams of apremilast twice daily or received a placebo.

By month four, nearly 60% of patients achieved a meaningful benchmark: Psoriasis Area and Severity Index (PASI) 75. This is a measurement indicating 75% improvement in the amount of skin surface area covered by plaques. In comparison, fewer than 13% in the placebo group and 35% in the apremilast group reached PASI 75.

Additionally, plaques cleared or nearly cleared in more than half of the people treated with deucravacitinib. That’s in contrast to only about 7% of people in the control group.

Patients who took deucravacitinib continued to improve over time. After six months of treatment, 69% reached PASI 75 compared with 38% of those who took apremilast.

More Accessible, Fewer Side Effects

For people with moderate to severe plaque psoriasis, providers often prescribe injections or biologics which can alter the immune system to slow or stop disease progression. (Topical treatments are typically reserved for plaque psoriasis that only covers a small part of someone's body.)

There are some existing psoriasis treatments that can be given orally, such as Trexall (methotrexate) and Gengraf, Neoral, or Sandimmue (cyclosporine), but they tend to be less effective or lead to more serious side effects than the injectable options.

Biologic drugs are given by injection or intravenously and target specific portions of the immune system. These include Humira (adalimumab), Enbrel (etanercept), and Stelara (ustekinuman). These options can be expensive and may not be covered by insurance.

Both biologic and non-biologic immunosuppressant drugs often raise the risk of infection and other health problems. Patients who take them often need to be monitored routinely.

Deucravacitinib, meanwhile, more specifically targets a key enzyme rather than suppressing the immune system broadly. This approach, Armstrong said, makes it a safer alternative to the other available drugs.

How Does Deucravacitinib Work?

The drug is the first to target tyrosine kinase 2 (TYK2), an enzyme that is linked to susceptibility for psoriasis. 

TYK2 is a member of the Janus kinase (JAK) family. Many treatments for autoimmune disorders target JAKs, but most JAK inhibitors don’t do much to affect TYK2. By blocking this specific enzyme, the drug interrupts some of the cellular processes that are key for forming psoriatic lesions.

Plus, a TYK2 inhibitor drug could be safer because it has a narrow target, compared to other JAK inhibitors, which can have a broad effect on the immune system.  

“By having more specific targeting of the pathways that are involved in psoriasis, we avoid essentially hitting the other pathways that are important for our normal human functions,” Armstrong said. These include the effects on blood cell counts, lipid and other types of metabolism, and other types of immunity.

Deucravacitinib works similarly to the widely-used psoriasis biologic agent Stelara (ustekinumab). But that drug is a monoclonal antibody that needs to be injected in a hospital setting. Deucravacitinib, on the other hand, comes as an oral pill that patients can easily take at home or while travelling.

How to Take It

Deucravacitinib is much simpler to take than most of the other injectable biologic drugs currently on the market. The 6-milligram pill is taken once a day. It can be taken with or without food.

The drug should be most effective after five to six months of treatment, but most patients will start to see improvement within just a few weeks, Armstrong said.

There are no known drug-drug interactions, so patients can use deucravacitinib alongside treatments for other conditions.

In clinical trials, patients who took deucravacitinib were less likely to discontinuation the treatment than those taking apremilast.

“Patients—once they are on the medication—tend to stay on the medication," Armstrong said.

As with many chronic conditions, pausing or stopping treatment may allow the condition to re-emerge.  

Known Side Effects

In clinical trials, the most common adverse events associated with deucravacitinib were the common cold, upper respiratory tract infection, headache, diarrhoea, and nausea.

More than 1% of patients who took deucravacitinib experienced upper respiratory infection, increased levels of creatine phosphokinase (CK) in the blood, herpes simplex, mouth ulcers, acne, or inflammation of the hair follicles (folliculitis).

More people who took deucravacitinib experienced adverse events than those who took the placebo. However, only 2% of participants stopped the treatment due to serious adverse events compared with 4% in the placebo group.

Additionally, there were no herpes zoster infections, opportunistic infections, thromboembolic events, hematologic or lipid abnormalities that are characteristic of JAK1, JAK2, and JAK3 inhibitors.

Armstrong said people with severe liver disease should not take deucravacitinib. It should also not be taken along with other immunosuppressants.

What This Means For You

If you have moderate to severe plaque psoriasis, talk with a health provider about whether you should take deucravacitinib to control your condition.

https://www.verywellhealth.com/fda-approves-first-once-daily-oral-plaque-psoriasis-drug-6735912