WCD/EULAR 2019: Key Advances in IL-17A/23 Biologics and JAK Inhibitors Highlighted in Recent Filings

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The 2019 World Congress of Dermatology (WCD) and the 2019 Annual European Congress of Rheumatology (EULAR) were recently held in Milan and Madrid, respectively, where multiple pharmaceutical companies announced the latest research progress on their drugs. The following is a summary by Sina Medicine editors of significant advances in IL-17A/23 biologics and JAK inhibitors.

1. AbbVie Skyrizi

At WCD, AbbVie announced two-year data from the Phase III IMMhance clinical study of Skyrizi for the treatment of moderate-to-severe plaque psoriasis. The study consisted of two phases: in the first phase, patients were randomized to receive either Skyrizi or placebo; in the second phase, patients who received Skyrizi and achieved sPGA 0/1 remission at Week 28 were re-randomized to either continue Skyrizi treatment or switch to placebo.

The results showed that at Week 94, a substantially high proportion of patients who continued Skyrizi treatment achieved complete clearance of skin plaques: 73% achieved sPGA 0 remission, and 72% achieved PASI 100 remission. Among patients who switched to placebo and lost remission at or after Week 32, 84% regained complete or almost complete clearance of skin plaques upon resuming Skyrizi treatment.

Skyrizi is a selective IL-23-targeting antibody therapy that selectively blocks the immune inflammatory mediator IL-23 in the body by specifically binding to the IL-23p19 subunit. EvaluatePharma predicts that the drug’s sales will reach $2.2 billion in 2024.

2. Eli Lilly Taltz

At the WCD conference, Eli Lilly presented 5-year data from the Phase III UNCOVER-1 study evaluating Taltz for the treatment of moderate-to-severe plaque psoriasis. In this study, patients who achieved sPGA 0/1 response at Week 12 and completed 60 weeks of treatment entered an open-label extension phase to continue receiving Taltz therapy.

The results showed that patients maintained a high level of skin plaque clearance during treatment: sustained response was observed from Week 60 to Week 264, with PASI 75, 90, and 100 response rates of 94.3%, 81.8%, and 46.6%, respectively, at Week 264.

Taltz is an antibody therapy that selectively targets IL-17A, binding to it with high affinity and specificity to block its interaction with the IL-17 receptor. EvaluatePharma predicts that the drug’s sales will reach $2.707 billion in 2024.

3. Novartis Cosentyx

At the EULAR Congress, Novartis announced new data from the Phase IIIb MAXIMISE study evaluating Cosentyx for the management of axial manifestations in psoriatic arthritis (PsA). The study enrolled PsA patients with diagnosed axial involvement. Results showed that at Week 12, the study met its primary and key secondary endpoints: 63.1% and 66.3% of patients in the Cosentyx 300 mg and 150 mg groups, respectively, achieved ASAS20 response, compared to only 31.3% in the placebo group. Furthermore, patients treated with Cosentyx demonstrated early, rapid, and significant improvement in symptoms and signs of PsA with axial manifestations as early as Week 4.

These are the first data demonstrating the efficacy and safety of a biologic agent in managing axial manifestations of psoriatic arthritis (PsA).

Novartis also announced new data from the Phase III FUTURE 5 study of Cosentyx for the treatment of psoriatic arthritis (PsA). The study evaluated the impact of Cosentyx on the signs and symptoms of PsA, as well as its inhibition of radiographic progression in PsA. The results showed that nearly 90% of patients treated with Cosentyx for two years demonstrated no radiographic progression.

Cosentyx is the first biologic agent that specifically targets and inhibits IL-17A. It was approved for market launch in January 2015 and has currently been approved for three indications: Psoriatic Arthritis (PsA), psoriasis, and ankylosing spondylitis. Its sales revenue in 2018 amounted to $2.837 billion. EvaluatePharma predicts that the global sales of this drug are expected to reach $5.5 billion by 2024.

4. AbbVie upadacitinib

At the EULAR Annual Meeting, AbbVie presented new data from two Phase III studies, SELECT-EARLY and SELECT-COMPARE, evaluating the JAK inhibitor upadacitinib for the treatment of moderate-to-severe active rheumatoid arthritis (RA).

The results showed that clinical remission, as assessed by ACR20/50 and DAS28-CRP < 2.6, was significantly improved in terms of RA symptoms and signs after 48 weeks of once-daily oral upadacitinib treatment (SELECT-EARLY study: 15 mg or 30 mg doses; SELECT-COMPARE study: 15 mg plus methotrexate). Furthermore, pooled safety analysis data from five Phase III SELECT clinical studies demonstrated a consistent safety profile of upadacitinib in patients with moderate to severe active RA.

Upadacitinib is an oral selective JAK1 inhibitor. The drug’s application for the treatment of rheumatoid arthritis (RA) is currently under review in the United States, with AbbVie utilizing a priority review voucher purchased for $350 million to expedite the review process. EvaluatePharma predicts that the drug’s sales will reach $2.57 billion in 2024.

SELECT-EARLY Study Results:

Results of the SELECT-COMPARE Study:

5. Eli Lilly's Olumiant

At the EULAR Annual Congress, Eli Lilly presented updated integrated safety data from additional Phase III trials and long-term extension studies evaluating Olumiant for the treatment of moderate-to-severe active rheumatoid arthritis (RA). The results showed that over a treatment period of up to 7 years, the incidence of adverse events in patients receiving once-daily oral Olumiant at a 4 mg dose was similar to that in the placebo group; notably, there were no significant differences in the incidence of deep vein thrombosis or pulmonary embolism. The updated data also revealed that the 4 mg dose differed significantly from placebo in only one category of adverse events, namely a higher incidence of herpes infections compared with placebo. In contrast, the 2 mg dose showed no significant differences from placebo in any safety category.

Last April, the FDA approved only the 2 mg dose of Olumiant for the treatment of rheumatoid arthritis (RA), rejecting the 4 mg dose due to safety concerns and adding a boxed warning to the label highlighting risks of infection, malignancy, and thrombosis. The data released this time may help alleviate the FDA’s concerns regarding the 4 mg dose of Olumiant.

On June 15, Eli Lilly will present detailed data from two Phase III studies of Olumiant monotherapy for atopic dermatitis at the WCD conference: The studies met their primary endpoints, with a significantly higher proportion of patients in the Olumiant treatment group achieving an AD IGA score of clear or almost clear (IGA 0/1) at Week 16 compared to the placebo group.

Olumiant is a selective, reversible JAK1/2 inhibitor developed for the treatment of various inflammatory and autoimmune diseases. EvaluatePharma predicts that global sales of Olumiant are expected to reach $1.5 billion in 2024.

6. Pfizer Xeljanz XR

At the EULAR Annual Meeting, Pfizer announced positive data from the ORAL Shift study, a Phase 3b/4 trial evaluating the JAK inhibitor Xeljanz XR for the treatment of moderate-to-severe active rheumatoid arthritis (RA). In this study, patients who achieved low disease activity (LDA) after receiving Xeljanz XR plus methotrexate (MTX) during a 24-week open-label lead-in period were randomized to either continue combination therapy with Xeljanz XR plus MTX or switch to Xeljanz XR monotherapy.

The results showed that the study met its primary endpoint: Xeljanz XR monotherapy demonstrated non-inferiority to Xeljanz XR + MTX combination therapy in terms of disease activity assessed by the change in DAS28-4[ESR] score from randomization at Week 24 to the end of the double-blind period at Week 48 (0.33 vs. 0.03; non-inferiority p < 0.0005).

This is the only study to date confirming that, in patients with moderate-to-severe active rheumatoid arthritis (RA) who achieve low disease activity with combination therapy of a JAK inhibitor plus methotrexate (MTX), discontinuation of MTX while continuing JAK inhibitor monotherapy can maintain efficacy.

Xeljanz, approved in 2012 as the first JAK inhibitor launched globally, generated $1.774 billion in sales in 2018. However, safety concerns surrounding the high dose (10 mg) have persisted. In the first half of this year, both the U.S. FDA and the European EMA issued safety warnings and restrictions on 10 mg Xeljanz due to pulmonary embolism and an imbalance in mortality rates.

References:

1、New Two-Year Data at the 24th World Congress of Dermatology Shows SKYRIZI (risankizumab) Maintains Complete Skin Clearance

2、Lilly to Present 5-Year Sustained Efficacy and Safety Results for Taltz (ixekizumab) in Patients with Plaque Psoriasis at the World Congress of Dermatology

3、Novartis Cosentyx first to show efficacy in all key manifestations of psoriatic arthritis

4、New Long-Term Data from Upadacitinib Phase 3 Studies in Rheumatoid Arthritis Including Results on Clinical Remission at 48 Weeks Presented at EULAR

5、Look here, FDA: Eli Lilly touts Olumiant safety data for unapproved high dose

6、Pfizer Announces Results from XELJANZ XR (tofacitinib) ORAL Shift Study, The First Phase 3b/4 Study to Evaluate Methotrexate Withdrawal with a JAK Inhibitor