Interleukin inhibitors are rising as the newest psoriasis treatment.

Tumor necrosis factor-α (TNF-α) inhibitors, the first-generation biological agents for the skin condition, have been used as the primary remedy for 15 years. However, interleukin inhibitors are ready to take over their place.

Interleukin inhibitors came under the spotlight when studies found that immune cell TH17 was the major cause of psoriasis, and the most cytokine produced in TH17 cells was interleukin-17A (IL-17A).

IL-17A inhibitors are known to be superior to other TNF-α inhibitors or IL-12 / IL-23 inhibitors because IL-17A inhibitors selectively bind to IL-17A proteins to suppress inflammation.

Novartis’ Cosentyx (secukinumab) and Lilly’s Taltz (ixekizumab) are authorized IL-17A inhibitors in Korea.

Novartis’ psoriasis treatment Cosentyx (left) and Lilly’s Taltz

Cosentyx backed by abundant clinical evidence, long-term data

As the first developed IL-17A, Cosentyx has more clinical data than Taltz.

In the phase-3 CLEAR study that compared Cosentyx with IL-12 / IL-23 inhibitor ustekinumab, Cosentyx (79 percent) was superior to ustekinumab (57.6 percent) in achieving PASI 90 at 16th week. In the PASI 100 score, Cosentyx (44.3 percent) was also superior to ustekinumab (28.4 percent).

In another phase-3 FIXTURE trial, Cosentyx showed 77.1 percent achievement to reach PASI 75, whereas that of TNF-α inhibitor etanercept stood at 44 percent. Cosentyx’ Investigator’s Global Assessment (IGA) 0/1 responder rate was 62.5 percent, versus that of etanercept, 27.2 percent.

Cosentyx also proved five-year efficacy and safety in the SCULPTURE trial.

The multi-center, double-blind, and open-label trial was an extended version for five years from a phase-3 study. In the first year of treatment, Cosentyx’ PASI 75/90/100 achievement rate was 88.9 percent, 68.5 percent, and 43.8 percent, respectively. In the fifth year of treatment, it went up to 88.5 percent, 66.4 percent, and 41 percent, demonstrating the drug’s sustained efficacy and safety.

Cosentyx also displayed efficacy and safety for various symptoms from psoriasis on specific areas that are difficult to treat.

The medicine showed potency and safety to treat palmoplantar psoriasis in the GESTURE study, scalp psoriasis in SCALP, and psoriasis on the nail in TRANSFIGURE. Most recently, Cosentyx proved effectiveness for pustular psoriasis in the 2PRECISE trial and expanded indication in Japan.

Taltz also proved superiority to etanercept and ustekinumab in trials that directly compared them.

According to the results of UNCOVER-2 and UNCOVER-3 studies, Taltz’ PASI100 achievement rate at the 12th week was 40.5 percent and 37.7 percent, five times higher than etanercept’s 5.3 percent and 7.3 percent, respectively.

In the IXORA-S trial, Talz’ PASI100 achievement rate at the 12th week was 36 percent, 2.5 times higher than that of ustekinumab.

Lilly uses indirect comparisons between Talz and Cosentyx

Lilly is carrying out indirect comparison studies to prove how Taltz can overcome Cosentyx’ weakness.

A study published in the British Journal of Dermatology compared Taltz’ efficacy for moderate or severe plaque psoriasis and a phase-3 study on Cosentyx.

The result showed that Taltz had 10-12.7 percent and 11.7-13.1 percent higher ratios in PASI90 and PASI100, respectively than Cosentyx.

Cosentyx shows long-term efficacy, suppression of radiological progression in psoriatic arthritis

About 10 percent of local psoriasis patients are accompanying psoriatic arthritis. Whether a medicine has an indication for psoriatic arthritis is a significant factor for patients to choose a treatment option.

Both Consentyx and Taltz have an indication for psoriatic arthritis, but only Cosentyx is reimbursable.

Cosentyx was the first drug to obtain approval as a psoriasis treatment in September 2015. The medication’s indication includes psoriatic arthritis and rheumatoid spondylitis. The drug is reimbursable in all three indications only for severely ill patients.

Taltz won the nod for psoriasis treatment in December 2017 and additional indication for psoriatic arthritis in December 2018.

Cosentyx is superior to Taltz in terms of the scope of indications and insurance benefits. The former also has much more abundant clinical data for psoriatic arthritis than the latter.

Cosentyx demonstrated efficacy and safety in patients with psoriatic arthritis in the FUTURE 1 study. Later on, it also showed long-term effectiveness and inhibition of radiological progression in the FUTURE 2-5 trials.

The phase-3 FUTURE 1 study was on 606 patients with active psoriatic arthritis, and Cosentyx showed superiority to the placebo in achieving American College of Rheumatology (ACR) 20 response (20 percent improvement in disease activity compared to the baseline) at the 24th week of treatment. Later, 460 patients participated in the three-year extended study for the assessment of the drug’s five-year long-term effect.

Patients treated with Cosentyx have steadily improved in signs and symptoms of psoriatic arthritis during the five years. Among them, 83 percent and 94 percent reached complete remission in enthesitis and hand and toe arthritis, respectively.

Extended studies of FUTURE recently showed that most of the patients did not have a radiological progression during the three years.

Taltz was also effective and safe in patients with psoriatic arthritis in SPIRIT-P1 and SPIRIT-P2 trials.

In the SPIRIT-P1 study on patients who have not been treated with disease-modifying antirheumatic drugs (DMARDs), 58 percent of those treated with Taltz achieved ACR20 response at the 24th week, almost twice higher than 30 percent of the placebo-given group.

In the SPIRIT-P2 trial on patients who failed in one or two TNF-α inhibitors treatment, 53 percent of those treated with Taltz achieved ACR20 response at the 24th week, 2.5 times higher than 20 percent of the placebo group.

Taltz’ administration reduced to half compared to that of Cosentyx

To treat plaque psoriasis, 160mg of Taltz is subcutaneously injected at the zero week (80mg each for twice), 80mg (once) at the second, fourth, sixth, eighth, 10th, and 12th week. Then, 80mg is given every four weeks.

In the case of Cosentyx, 300mg is injected at the zero, first, second, third, and fourth week (150mg each for two times), then, 300mg once a month.

Except for the first administration, 80mg of Talz is given only once for one session of treatment. After 12 weeks, Taltz is given only once a month, which is less frequent than Cosentyx. In the first year of treatment, Taltz is administered 17 times, much less than Cosentyx which needs 32 times of administration.

“Taltz has the least number of injections among the same classes of treatments, contributing to an improvement of the quality of life of psoriasis patients,” Lilly said.

Both Novartis and Lilly are operating programs to support psoriasis patients.

Novartis has a call center where professional counseling nurses provide tips for self-injection of Cosentyx. The company also offers a mobile application to help patients record their health status and use the information for diagnosis, and a “patient support kit” service.

Lilly’s patient support program “Touch 365” provides information about Taltz, medication schedule, accompanying diseases of severe psoriasis and other information necessary for everyday life for psoriasis patients.

In summary, Cosentyx has a competitive edge over Taltz in the scope of indication in psoriasis treatment and insurance coverage for psoriatic arthritis.

However, as Taltz signaled a better therapeutic effect in indirect comparison studies with Cosentyx, Taltz has an ample chance to take over Cosentyx through real-world study results in the future.

kym@docdocdoc.co.kr

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