Psoriasis: New biologics coming closer to market

Key Points

Newer biologics to treat the condition are currently in late stages of development, and promising data from phase 2 and phase 3 clinical trials should give patients reason to hope. Availability may be as early as the end of 2008 or during 2009, according to presenters at two separate meetings held here earlier this year.

"When biologics first came out, there was a lot of skepticism that they would be more effective than other systemics we have," according to Mark Lebwohl, M.D., at the Winter Clinical Dermatology Conference.

"Future biologics for psoriasis are likely to be more safe, more effective and more convenient than past biologic therapies for this disease," says Andrew Blauvelt, M.D., professor in the department of dermatology and professor in the department of molecular microbiology and immunology at Oregon Health & Science University, Portland, Ore.

At a psoriasis symposium at the MauiDerm 2008 meeting, Dr. Blauvelt shared phase 3 findings for Centocor's ustekinumab and phase 2 results for Abbott's ABT-874. Both drugs target the p40 subunit that is common to interleukin 23 (IL-23) and interleukin 12 (IL-12).

"The drugs target two cytokines - IL-23 and IL-12. However, blockade of IL-23 and not IL-12 is probably the main reason why these drugs are proving so effective in psoriasis," he says.

"IL-23 is an important new target for psoriasis biologics.

"This cytokine and its downstream cytokine mediators appear to be critical in initiating and maintaining inflammation in psoriasis," Dr. Blauvelt tells Dermatology Times.

USTEKINUMAB

The phase 3 study's dosing of ustekinumab differed from the usual for biologics, Dr. Blauvelt says, because patients were given the drug (or placebo) at weeks zero, four and then every 12 weeks indefinitely.

In three treatment arms, patients received either a low dose (45 mg) or high dose (90 mg) of ustekinumab or were randomized to placebo for the first four weeks and then split into low- (45 mg) and high-dose (90 mg) treatment groups.

Results indicated that after just two doses (at weeks zero and four) of ustekinumab, 67 percent of the subjects who received the low dose had a PASI-75 response at week 12.

Among the high-dose group, 76 percent achieved PASI-75 at week 12. The researchers also used the Physicians' Global Assessment (PGA) to evaluate patients' drug responses. The proportion of subjects who were cleared or had minimal lesions at week 12 was 68 percent of the low-dose group and 73 percent of the high-dose group.

Dr. Lebwohl says that the 12-week dosing schedule is unique and beneficial.

"We don't have any other treatment that is given every three months," he says.

Dr. Lebwohl is the Sol & Clara Kest professor and chairman in the department of dermatology at Mt. Sinai School of Medicine, New York, and senior author on the first publication of ustekinumab's phase 2 trial results.

Patients in the ustekinumab trial were then evaluated at week 28 after receiving three doses (at weeks zero, four and 16). PASI response remained strong, with 70 percent of low-dose and 79 percent of high-dose subjects maintaining PASI-75 at week 28. A smaller, but still respectable, portion of patients maintained PASI-90 at week 28: 45 percent of low-dose and 54 percent of high-dose subjects.

To evaluate PASI response after treatment withdrawal, the researchers continued injections through week 40 and then administered placebo. Of the patients in the low-dose group who achieved PASI-75 at week 40, 20 percent maintained that response by week 76. For the high-dose group, 18 percent of patients who were PASI-75 at week 40 were still at that level at week 76.

"The drug does wear off over time if you stop treatment, but there is not a rapid recurrence of disease. It is not a rebound phenomenon that we see with some other drugs," Dr. Lebwohl says.

Safety through week 12 was "similar between drug and placebo," according to Dr. Blauvelt.

No cases of active tuberculosis or serious opportunistic infections were noted. For instance, the proportion of patients experiencing one or more adverse events was 49.3 percent for placebo, 52.6 percent for low-dose ustekinumab and 47.9 percent for high-dose ustekinumab.

Dr. Lebwohl says that, as with any medication that targets the immune system, "You would expect an increase in infection, but we did not see it."