FDA panel unanimously supports secukinumab approval for psoriasis

SILVER SPRING, MD. – The human monoclonal antibody secukinumab is expected to be the first biologic that targets interleukin-17A to be approved by the agency for treating psoriasis, with a Food and Drug Administration advisory panel’s unanimous support for the approval.

At a meeting on Oct. 20, the FDA’s Dermatologic and Ophthalmic Drugs Advisory committee voted 7-0 to recommend approval of secukinumab for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, the indication proposed by Novartis Pharmaceuticals. Secukinumab “selectively binds and neutralizes” IL-17A, a proinflammatory cytokine “that is involved in normal inflammatory and immune responses and plays a key role in the pathogenesis of plaque psoriasis,” according to the company.

If approved, secukinumab would be the first IL-17A blocker available and would be available in a lyophilized formulation for reconstitution, and in a liquid formulation in a refilled syringe or autoinjector pen. The 300-mg dose was determined to be the best dose to achieve clear or almost clear skin, with a favorable safety profile that was comparable to that of the 150-mg dose, which was also studied in phase II and III studies, according to Novartis. The company has proposed a dose of 300 mg, administered with a subcutaneous injection, at 0, 1, 2, 3, and 4 weeks, followed by 300 mg once a month.

The panel agreed that the 300-mg dose was effective with an acceptable risk-benefit profile, but agreed that it would be useful to have the 150-mg dose, which was also effective in trials, be available as well. The panel also recommended that the 450-mg dose, which was not formally studied, be evaluated further in postmarketing studies, because it could be useful in nonresponders and for heavier patients weighing 90 kg (about 198 pounds) or more, because of evidence that the 300-mg dose was less effective in heavier patients.

Secukinumab has been studied in 10 phase II and III studies of almost 4,000 patients with psoriasis. In the two main phase III studies, the 150-mg and 300-mg doses were compared with placebo (and to a formulation of etanercept not available in the United States in one study); the primary endpoints were the Psoriasis Area and Severity Index (PASI) 75, a 75% improvement of psoriasis from baseline, and an Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear skin).

In one study of 738 patients, PASI 75 scores at 12 weeks were achieved by almost 82% and almost 72% of those on the 300-mg and 150-mg doses respectively, vs. 4.5% of those on placebo. In the second study, PASI 75 scores at 12 weeks were achieved by 77% and 67% of those on the 300-mg and 150-mg doses respectively, vs. almost 5% of those on placebo. About 63%-65% of those on the 300-mg dose and about 51% of those on the 150-mg dose had an IGA of 0/1 at 12 weeks, vs. about 2.4%-2.8% of those on placebo. Differences in the responses were sustained at week 52, according to Novartis.

Concentration of the drug decreases as body weight increases, and in studies, weight had a significant effect on efficacy results. The proportion of patients who achieved the PASI 75 and IGA 0/1 endpoints was higher among those weighing under 90 kg than those weighing 90 kg or more at both the 150-mg and 300-mg doses tested.

Pooled data of phase III trial data were used to evaluate safety over 12 and 52 weeks. Serious infections, malignancies and serious cardiovascular events were low; there were no reports of reactivation of latent tuberculosis. No deaths were reported related to treatment. During the first 12 weeks of treatment, there was a higher rate of nonserious upper respiratory infections among the treated patients, and superficial Candida infections were more common among those on the 300-mg dose (1.2%) than among those on the 150-mg dose (0.4%) and placebo (0.3%). The FDA’s analysis of safety concluded that infection rates “tend to increase” as the concentration of secukinumab increases, but that most adverse events associated with greater exposure in patients weighing less than 90 kg were mild to moderate.

The panel agreed with the company’s plan to follow long-term safety in a postmarketing registry of patients with moderate to severe psoriasis, in at least 2,000 patients treated with secukinumab, 2,500 treated with other biologics, and 500 treated with other systemic medications. One panelist also recommended that long-term safety be evaluated in studies using large administrative databases for outcomes including malignancies and autoimmune events.

The FDA is expected to decide on approval by early 2015, according to Novartis, which plans to market secukinumab as Cosentyx if approved. The FDA usually follows the recommendations of its advisory panels. Members of these two panels had no conflicts to disclose; occasionally, panelists with a conflict are given a waiver, but not at this meeting. Secukinumab is not yet approved elsewhere, and is also under review in Europe. Phase III studies in patients with psoriatic arthritis are underway.

[email protected]

SILVER SPRING, MD. – The human monoclonal antibody secukinumab is expected to be the first biologic that targets interleukin-17A to be approved by the agency for treating psoriasis, with a Food and Drug Administration advisory panel’s unanimous support for the approval.

At a meeting on Oct. 20, the FDA’s Dermatologic and Ophthalmic Drugs Advisory committee voted 7-0 to recommend approval of secukinumab for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, the indication proposed by Novartis Pharmaceuticals. Secukinumab “selectively binds and neutralizes” IL-17A, a proinflammatory cytokine “that is involved in normal inflammatory and immune responses and plays a key role in the pathogenesis of plaque psoriasis,” according to the company.

If approved, secukinumab would be the first IL-17A blocker available and would be available in a lyophilized formulation for reconstitution, and in a liquid formulation in a refilled syringe or autoinjector pen. The 300-mg dose was determined to be the best dose to achieve clear or almost clear skin, with a favorable safety profile that was comparable to that of the 150-mg dose, which was also studied in phase II and III studies, according to Novartis. The company has proposed a dose of 300 mg, administered with a subcutaneous injection, at 0, 1, 2, 3, and 4 weeks, followed by 300 mg once a month.

The panel agreed that the 300-mg dose was effective with an acceptable risk-benefit profile, but agreed that it would be useful to have the 150-mg dose, which was also effective in trials, be available as well. The panel also recommended that the 450-mg dose, which was not formally studied, be evaluated further in postmarketing studies, because it could be useful in nonresponders and for heavier patients weighing 90 kg (about 198 pounds) or more, because of evidence that the 300-mg dose was less effective in heavier patients.

Secukinumab has been studied in 10 phase II and III studies of almost 4,000 patients with psoriasis. In the two main phase III studies, the 150-mg and 300-mg doses were compared with placebo (and to a formulation of etanercept not available in the United States in one study); the primary endpoints were the Psoriasis Area and Severity Index (PASI) 75, a 75% improvement of psoriasis from baseline, and an Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear skin).

In one study of 738 patients, PASI 75 scores at 12 weeks were achieved by almost 82% and almost 72% of those on the 300-mg and 150-mg doses respectively, vs. 4.5% of those on placebo. In the second study, PASI 75 scores at 12 weeks were achieved by 77% and 67% of those on the 300-mg and 150-mg doses respectively, vs. almost 5% of those on placebo. About 63%-65% of those on the 300-mg dose and about 51% of those on the 150-mg dose had an IGA of 0/1 at 12 weeks, vs. about 2.4%-2.8% of those on placebo. Differences in the responses were sustained at week 52, according to Novartis.

Concentration of the drug decreases as body weight increases, and in studies, weight had a significant effect on efficacy results. The proportion of patients who achieved the PASI 75 and IGA 0/1 endpoints was higher among those weighing under 90 kg than those weighing 90 kg or more at both the 150-mg and 300-mg doses tested.

Pooled data of phase III trial data were used to evaluate safety over 12 and 52 weeks. Serious infections, malignancies and serious cardiovascular events were low; there were no reports of reactivation of latent tuberculosis. No deaths were reported related to treatment. During the first 12 weeks of treatment, there was a higher rate of nonserious upper respiratory infections among the treated patients, and superficial Candida infections were more common among those on the 300-mg dose (1.2%) than among those on the 150-mg dose (0.4%) and placebo (0.3%). The FDA’s analysis of safety concluded that infection rates “tend to increase” as the concentration of secukinumab increases, but that most adverse events associated with greater exposure in patients weighing less than 90 kg were mild to moderate.

The panel agreed with the company’s plan to follow long-term safety in a postmarketing registry of patients with moderate to severe psoriasis, in at least 2,000 patients treated with secukinumab, 2,500 treated with other biologics, and 500 treated with other systemic medications. One panelist also recommended that long-term safety be evaluated in studies using large administrative databases for outcomes including malignancies and autoimmune events.

The FDA is expected to decide on approval by early 2015, according to Novartis, which plans to market secukinumab as Cosentyx if approved. The FDA usually follows the recommendations of its advisory panels. Members of these two panels had no conflicts to disclose; occasionally, panelists with a conflict are given a waiver, but not at this meeting. Secukinumab is not yet approved elsewhere, and is also under review in Europe. Phase III studies in patients with psoriatic arthritis are underway.

[email protected]

SILVER SPRING, MD. – The human monoclonal antibody secukinumab is expected to be the first biologic that targets interleukin-17A to be approved by the agency for treating psoriasis, with a Food and Drug Administration advisory panel’s unanimous support for the approval.

At a meeting on Oct. 20, the FDA’s Dermatologic and Ophthalmic Drugs Advisory committee voted 7-0 to recommend approval of secukinumab for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, the indication proposed by Novartis Pharmaceuticals. Secukinumab “selectively binds and neutralizes” IL-17A, a proinflammatory cytokine “that is involved in normal inflammatory and immune responses and plays a key role in the pathogenesis of plaque psoriasis,” according to the company.

If approved, secukinumab would be the first IL-17A blocker available and would be available in a lyophilized formulation for reconstitution, and in a liquid formulation in a refilled syringe or autoinjector pen. The 300-mg dose was determined to be the best dose to achieve clear or almost clear skin, with a favorable safety profile that was comparable to that of the 150-mg dose, which was also studied in phase II and III studies, according to Novartis. The company has proposed a dose of 300 mg, administered with a subcutaneous injection, at 0, 1, 2, 3, and 4 weeks, followed by 300 mg once a month.

The panel agreed that the 300-mg dose was effective with an acceptable risk-benefit profile, but agreed that it would be useful to have the 150-mg dose, which was also effective in trials, be available as well. The panel also recommended that the 450-mg dose, which was not formally studied, be evaluated further in postmarketing studies, because it could be useful in nonresponders and for heavier patients weighing 90 kg (about 198 pounds) or more, because of evidence that the 300-mg dose was less effective in heavier patients.

Secukinumab has been studied in 10 phase II and III studies of almost 4,000 patients with psoriasis. In the two main phase III studies, the 150-mg and 300-mg doses were compared with placebo (and to a formulation of etanercept not available in the United States in one study); the primary endpoints were the Psoriasis Area and Severity Index (PASI) 75, a 75% improvement of psoriasis from baseline, and an Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear skin).

In one study of 738 patients, PASI 75 scores at 12 weeks were achieved by almost 82% and almost 72% of those on the 300-mg and 150-mg doses respectively, vs. 4.5% of those on placebo. In the second study, PASI 75 scores at 12 weeks were achieved by 77% and 67% of those on the 300-mg and 150-mg doses respectively, vs. almost 5% of those on placebo. About 63%-65% of those on the 300-mg dose and about 51% of those on the 150-mg dose had an IGA of 0/1 at 12 weeks, vs. about 2.4%-2.8% of those on placebo. Differences in the responses were sustained at week 52, according to Novartis.

Concentration of the drug decreases as body weight increases, and in studies, weight had a significant effect on efficacy results. The proportion of patients who achieved the PASI 75 and IGA 0/1 endpoints was higher among those weighing under 90 kg than those weighing 90 kg or more at both the 150-mg and 300-mg doses tested.

Pooled data of phase III trial data were used to evaluate safety over 12 and 52 weeks. Serious infections, malignancies and serious cardiovascular events were low; there were no reports of reactivation of latent tuberculosis. No deaths were reported related to treatment. During the first 12 weeks of treatment, there was a higher rate of nonserious upper respiratory infections among the treated patients, and superficial Candida infections were more common among those on the 300-mg dose (1.2%) than among those on the 150-mg dose (0.4%) and placebo (0.3%). The FDA’s analysis of safety concluded that infection rates “tend to increase” as the concentration of secukinumab increases, but that most adverse events associated with greater exposure in patients weighing less than 90 kg were mild to moderate.

The panel agreed with the company’s plan to follow long-term safety in a postmarketing registry of patients with moderate to severe psoriasis, in at least 2,000 patients treated with secukinumab, 2,500 treated with other biologics, and 500 treated with other systemic medications. One panelist also recommended that long-term safety be evaluated in studies using large administrative databases for outcomes including malignancies and autoimmune events.

The FDA is expected to decide on approval by early 2015, according to Novartis, which plans to market secukinumab as Cosentyx if approved. The FDA usually follows the recommendations of its advisory panels. Members of these two panels had no conflicts to disclose; occasionally, panelists with a conflict are given a waiver, but not at this meeting. Secukinumab is not yet approved elsewhere, and is also under review in Europe. Phase III studies in patients with psoriatic arthritis are underway.

[email protected]