Drug in development may one day pack the power of a biologic into a pill, according to early trial results

| Melissa Leavitt

We all get used to making compromises in life. You may love your job but dread the commute. Your new home might be everything you’ve ever wanted … except for that wall-to-wall shag carpet. And when it comes to your psoriasis treatment, the effectiveness of a biologic could be just what you’re looking for … if only you didn’t have to deal with the needle.

Someday in the future, you might be able to trade injections and intravenous medication for a once-a-day pill. Clinical trial results for a new psoriasis drug in a very early stage of development raise the possibility that the precision of a biologic might one day become available as an oral treatment.

The pill, which is being developed by Vitae Pharmaceuticals, is currently called VTP-43742. It is still in the clinical trial testing phase and is not available to patients.

Targeted treatment options

One of the reasons biologics can be a good option for people with moderate-to-severe psoriasis is because they target specific parts of the immune system involved in the disease. They’re called cytokines, and they are pro-inflammatory proteins that are the culprits behind psoriasis inflammation.

New biologics like Cosentyx (secukinumab) and Taltz (ixekizumab), which studies have shown can deliver clear skin to large numbers of patients, block interleukin-17 (IL-17). Other biologics that are currently in development—including one by the company Boehringer Ingelheim that goes by the name BI655066, another by Merck and Sun Pharma called tildrakizumab, and guselkumab, a drug from Janssen—target IL-23. These drugs also have delivered notable improvements to patients, clinical trial results show.

VTP-43742 has these cytokines in the cross-hairs. According to Dr. Richard Gregg, Vitae’s chief scientific officer, it does this through a transcription factor called ROR gamma T.

Transcription factors carry out instructions from your body’s DNA that regulates the way your cells function. This one affects IL-17 and IL-23, two important cytokines involved in psoriasis.

VTP-43742 inhibits the action of ROR gamma T in a way that can affect the amount of both of these cytokines in the body, Gregg said.

Dr. James Krueger, a dermatologist and researcher at The Rockefeller University in New York and a paid consultant to Vitae, is enthusiastic about the potential effects of treating psoriasis by targeting ROR gamma T.

“The fact is it has been very hard to develop a drug to this target,” he said. “The target is right.”

Early trial results show once-a-day pill might improve psoriasis

Earlier this year, Vitae released trial results from a small Phase IIA trial showing how inhibiting ROR gamma T might affect psoriasis.

In the trial, a group of 15 people with moderate-to-severe psoriasis took the pill in a 350 milligram (mg) dose once a day for four weeks. This group included two patients on a placebo.

Another group of 15, with one on a placebo, took a 700 mg dose once a day. Both groups saw a statistically significant reduction in the severity of their psoriasis, as measured by the Psoriasis Area and Severity Index (PASI), according to a presentation released by Vitae.

At 29 percent, the reduction was greater for the 700 mg group, according to the data. The 350 mg group saw a 23 percent decrease.

In both groups, the improvements really started to take hold after about three weeks on the drug, according to Jeff Hatfield, Vitae’s CEO.

“In week one, you begin to see very slight changes in PASI. In week two, a little bit more. And then in weeks three and week four of the study, we saw a profound acceleration of change,” he said.

Laboratory tests also showed decreased levels of IL-17 in the skin and blood of people taking the drug, according to the results.

Krueger noted that because the study only lasted four weeks, it’s difficult to tell how effective the drug would ultimately be. The drug takes time to build up in the body, he explained. If given more time to take effect, the results may be different.

“The reductions that are measured here may not be the ultimate peak of reduction because this drug is only beginning to take effect,” he said.

Vitae’s drug may not ultimately be more effective than a biologic, Krueger said. But because it is a pill, it could be less expensive.

“It certainly would give the opportunity for lower cost and therefore better access for these drugs to the community,” Krueger said.

Learning more about drug safety

The drug was well tolerated, Hatfield said. Most side effects were minor and typical of many clinical studies, such as headache and nausea, and none of these occurred in more than 10 percent of patients, he said.

One patient taking the 700 mg pill dropped out of the study because of mild nausea and facial flushing, Hatfield said.

According to the data from Vitae, four patients taking the 700 mg dose experienced a liver side effect, which was measured by an increase in enzymes produced by the liver. The elevated liver enzymes went back to normal after the patients stopped the drug, and there was no other evidence of a liver side effect, according to the data.

Based only on the four-week trial results, it’s too soon to draw conclusions about the safety of the drug, Krueger said. But data about the side effects of other drugs that target IL-17 or IL-23—the cytokines affected by Vitae’s drug—could offer clues.

Stelara (ustekinumab) is a biologic that targets IL-23 as well as another cytokine, IL-12. It has been shown to have minimal risks associated with it, Krueger said.

“Over the years, ustekinumab has proven to be a very well tolerated and safe drug,” he said.

In terms of risks associated with blocking IL-17, people who are deficient in IL-17 are more at risk for mucocutaenous candidiasis or yeast infections, Krueger said. This has occurred in some patients on biologics that target IL-17 specifically.

Next steps on the clinical trial journey

Finishing the Phase IIA study is one milestone on the way to drug approval. But there is still a long way to go.

Hatfield described the goal of the Phase IIA trial of VTP-43742 in simple terms, designed “to answer a yes-no question—does it work or not as a mechanism?”

“The answer we got was ‘yes, this works,’” Hatfield said.

But there is still a lot to find out about the safety and effectiveness of the drug before it comes on the market. The next step is a Phase IIB trial, which will likely enroll a few hundred patients and is expected to begin later this year.

Wondering what other psoriasis and psoriatic arthritis drugs are currently being developed? Check out our pipeline.

 


Driving discovery, creating community

For more than 50 years, we’ve been driving efforts to cure psoriatic disease and improve the lives of those affected. But there’s still plenty to do! Learn how you can help our advocacy team shape the laws and policies that affect people with psoriasis and psoriatic arthritis – in your state and across the country. Help us raise funds to support research by joining Team NPF, where you can walk, run, cycle, play bingo or create your own fundraising event. If you or someone you love needs free, personalized support for living a healthier life with psoriatic disease, contact our Patient Navigation Center. And keep the National Psoriasis Foundation going strong by making a donation today. Together, we will find a cure.

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