UCB’s Cimzia Set To Make A Late Entrance At Psoriasis Party
Executive Summary
UCB has reported positive data from the final Phase III trial of its anti-TNF product Cimzia in plaque psoriasis, paving the way for approval applications later this year, but the product will have to elbow its way into a competitive market already under the shadow of a biosimilar threat.
UCB SAand its partner Dermira Inc. now have positive data from the last of three Phase III trials necessary to file its pegylated anti-TNF product Cimzia (certolizumab) for use in moderate to severe plaque psoriasis in the US, EU and Canada, and are scheduling submissions for the third quarter of 2017.
The new top-line data from the CIMPACT study will be added to previously reported results from the CIMPASI-1 and CIMPASI-2 trials to support its use in this disease. If successful, this could be the sixth US indication for the product.
Cimzia was launched in 2008 for Crohn’s disease and since then the product has taken the traditional approval path followed by other anti-TNF biologics by expanding its indications to include a range of autoimmune conditions: adults with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. An application for approval to treat juvenile arthritis also was filed in the US last year.
The product has proved a blockbuster for UCB and instrumental in helping the company overcome the loss of patent protection for previous blockbusters – the antihistamine Zyrtec (cetirizine) and the epilepsy treatment Keppra (levetiracetam). But Cimzia’s value mainly lies in the rheumatoid arthritis indication, which accounts for the lion’s share of its sales and most of its future sales potential. Analysts at Credit Suisse predicted 2016 sales of €901m in rheumatoid arthritis, compared with €264m in Crohn’s and €99m in other indications. This would reflect strong growth on 2015’s figures of €738m, €250m and €86m, respectively.
Good news for Cimzia is welcome after UCB’s big pipeline hope romosozumab (partnered with Amgen Inc.) produced mixed data from the Phase III FRAME study early last year. Observers now keenly await the results of the Phase III ARCH study due in the first half of this year, which will pit the novel osteoporosis drug head to head with alendronate and hopefully provide UCB with a clearly differentiated product.
Dermira Deal
UCB entered into a deal with Dermira Inc. in 2014 to develop and commercialize Cimzia in dermatology in the US, EU and Canada, with psoriasis as the particular focus. Dermira took on responsibility for Phase III development costs for payments of up to $49.5m for development and regulatory milestones. If approved in psoriasis, Dermira will have an exclusive license to commercialize Cimzia to dermatologists in the US and Canada. UCB will record the sales and Dermira will receive tiered royalty payments and up to $40m upon the achievement of tiered commercial milestones. (Also see "UCB entrusts Cimzia's psoriasis prospects to Dermira" - Scrip, 4 Jul, 2014.)
While additional sales in psoriasis would be welcome, analysts at Datamonitor Healthcare maintain that Cimzia’s late arrival and the advent of biosimilar TNF inhibitors will nonetheless hamper its uptake, even though the UCB drug’s history of safe use in rheumatoid arthritis and perceived comparable efficacy to Humira in psoriasis will boost its clinical attractiveness.
“If approved and launched, Cimzia will be the fourth anti-tumor necrosis factor (TNF) biologic to enter the psoriasis market, and will have to directly compete with AbbVie Inc./Eisai’s Humira (adalimumab) and Amgen/Pfizer Inc./Takeda Pharmaceutical Co. Ltd.’s Enbrel (etanercept), which are extremely well established as the preferred anti-TNFs. In addition, the increasing availability of lower-cost biosimilar versions of anti-TNF biologics, as well as highly efficacious interleukin inhibitors, will negatively impact Cimzia’s patient share,” according to Datamonitor.
The first etanercept biosimilar was approved in the EU a year ago in the first quarter of 2016, while the first etanercept and adalimumab biosimilars were approved in the US in the third quarter of 2016. “Furthermore, the increasing availability of highly efficacious IL inhibitors that target both biologic-naïve patients as well as TNF-refractory patients poses an additional threat to Cimzia’s potential in psoriasis. Key opinion leaders highlight that only novel mechanisms of action will be able to establish a strong foothold in the increasingly saturated psoriasis market,” Datamonitor said.
But the Credit Suisse analysts pointed out that the biosimilar threat in psoriasis is overblown, at least in the short term in the US. “Biosimilar Enbrel and Humira are not near-threats: We believe the biggest threat to Cimzia sales will come from biosimilar Enbrel or biosimilar Humira, which could cause more rapid price and volume erosion. However, Sandoz's biosimilar Enbrel, which was approved in the US in August 2016, is currently engaged in litigation with Amgen and unlikely to be available this decade. While AbbVie has guided for no biosimilar versions of Humira will be able to enter the US market until 2022.” Cimzia has patent protection until 2024.
CIMPACT Data
CIMPACT randomized 559 patients with moderate-to-severe chronic plaque psoriasis to one of four dosing arms — 400 mg of Cimzia every two weeks, 400 mg of Cimzia at weeks zero, two and four followed by 200 mg every two weeks, or 50 mg of Enbrel twice weekly, or placebo every two weeks.
At week 12, 66.7% of patients who received Cimzia 400 mg dose every two weeks and 61.3% of patients receiving the Cimzia 200 mg dose every two weeks achieved PASI 75 (the primary endpoint measure) compared with 5% for patients receiving placebo.
Also tested were response rates of Cimzia-treated patients to placebo-treated patients at week 16 using:
- PASI 75: 74.7% for patients receiving the 400 mg dose every two weeks and 68.2% for patients receiving the 200 mg dose every two weeks, compared with 3.8% for patients receiving placebo.
- At least a two-point improvement on a five-point Physician’s Global Assessment (PGA) scale to a final score representing clear or almost clear skin: 58.4% for the 400 mg dose-treated patients and 48.3% for the 200 mg dose-treated patients, compared with 3.4% for placebo.
UCB noted that the full data from all three CIMPACT trials would be submitted for presentation at a medical congress and to a peer-reviewed medical journal for publication.