Succession Plan: Skyrizi

One may boast the top-selling drug in the world for several years running and a market-leading position in a lucrative and innovation-ripe treatment space, but there’s always the need to plan for the future. That’s exactly what AbbVie, the big pharma immunology giant, has been undertaking in a series of deliberate actions designed to lessen the sting of looming revenue loss from generic competition to its rheumatoid arthritis (RA) stalwart Humira ($19.2 billion in 2019 sales), and maintain its strong hold in the market. So far, by all accounts, the North Chicago-based company is on a solid path to achieving that, and may be exceeding expectations.

While replacing Humira revenue figured significantly in AbbVie’s decision to acquire Allergan for $62 billion (the deal officially closed in May), the company was already long busy with preemptive preparations on the brand level, positioning a pair of newer medicines, Skyrizi (risankizumab) and Rinvoq (upadacitinib), approved last year for psoriasis and RA, respectively, to drive future growth and, combined, offset Humira losses (FDA has approved five generic versions of the tumor necrosis factor [TNF] inhibitor, though AbbVie has secured patent protection in the US that will prevent sales of Humira biosimilars until 2023; versions in Europe have been on the market since 2018).

Integral to the succession plan in particular has been the fast and successful launch of Skyrizi, approved in the US and Europe in April 2019 as a novel advancement in the treatment of moderate-to-severe plaque psoriasis. The drug is designed to work with a person’s immune system, attaching to interleukin-23 (IL-23), a key cytokine involved in inflammatory processes, and thought to be linked to a number of chronic immune-mediated diseases. By attaching to this protein, Skyrizi helps reduce the inflammation inside the body that leads to plaques on the skin. In a Phase III clinical trial that formed the basis of the drug’s approval, results showed that Skyrizi could clear skin lesions by 90% in up to three-quarters of patients within a week. It produced better skin clearance rates during clinical testing than similar drugs on the market, and has advantages in less-frequent dosing.

“We believe the main drivers of the strong product uptake following Skyrizi’s May 2019 launch were its differentiated clinical profile and quarterly administration, which has resonated with physicians and patients,” Elaine Sorg, president, US immunology and patient services, AbbVie, told Pharm Exec. Skyrizi recorded stronger-than-expected sales out of the gate, and in the three months from October to December 2019, reportedly posted $216 million in revenue, exceeding the company’s initial expectation of $150 million generated for the year.

During the 2019 launch period, Sorg says AbbVie saw strong prescription volume for Skyrizi, well above recent launch analogs in the psoriasis category. According to executives in AbbVie’s Q2 2019 earnings call, through the first 11 weeks of launch, the company already had about 1,700 prescribing physicians and roughly 3,750 patients had been treated with Skyrizi, including those in AbbVie’s bridge access program.

The company reported in its 1Q20 earnings call that, since the drug’s launch, it has established and expanded its in-play psoriasis patient share, which includes both new and switching patients to Skyrizi at more than 30%. The drug hit $330 million in sales in the second quarter of 2020, and as of August, in just 17 months on the market, has achieved $1 billion in cumulative US net sales.

Big backing

As alluded to, contributing to Skyrizi’s uptake has been the considerable support of dermatologists for next-generation biologics in what has become an increasingly crowded market for psoriasis treatments. In a survey of physicians released in June by J.P. Morgan, doctors expressed a clear preference for IL-23 inhibitors such as Skyrizi over the use of older drugs such as IL-17 and TNF inhibitors, lending to analyst belief that IL-23s will emerge as the go-to first-line psoriasis treatment over the next three years. Physicians cited superior efficacy, better tolerability, less frequent dosing, and experience of use as factors for the preference, “while payer coverage remains a work in progress,” the report states, also noting that J.P. Morgan analysts expect access to improve over time.

For Skyrizi specifically, the physicians surveyed see the monoclonal antibody as the preferred IL-23, with analysts expecting the product to continue gaining share within the IL-23 class. J.P. Morgan projects sales for Skyrizi to reach $4.5 billion by 2025.

Further evidence of a shift to the newer slate of biologics in psoriasis and atopic dermatitis was a survey of dermatologists conducted by MEDACorp, and cited in a late August report by Fierce Pharma, which attributed the findings to an investor’s note by SVB Leerink analyst Geoffrey Porges. According to Porges, responders favored prescribing Skyrizi and in-class competitors (Johnson & Johnson’s Tremfya, Sun Pharma’s Ilumya) over older treatments such as Amgen’s Otezla. The Fierce Pharma report notes that, in roughly three years, dermatologists predict the IL-23 class will account for around 18% of the total biologic market in moderate psoriasis patients and 29% in severe patients. Dermatologists believe Skyrizi will eventually secure around 60% of all IL-23 users, the report says.

In June, AbbVie released new head-to-head data in a Phase IIIb open-label study comparing Skyrizi and Novartis IL-17 blockbuster Cosentyx, which posted $3.6 billion in sales in 2019. The trial found that at 52 weeks, 66% of psoriasis patients receiving Skyrizi achieved completely clear skin—100% clearance in the Psoriasis Area and Severity Index (PASI)—versus 40% of patients receiving Cosentyx. Of patients treated with Skyrizi, 87% achieved 90% clearance in the PASI at week 52 compared to 57% of those administered Cosentyx.

Complementary pieces

With analysts still expecting Humira to retain market share and continue to grow in the US until its patent expires in 2023, AbbVie was challenged when launching Skyrizi to enter a market—one where it’s already a leader—nimbly enough to not risk cannibalizing Humira. Notably, last month, results released of a head-to-head trial between Skyrizi and Humira showed that Skyrizi was significantly superior in providing skin clearance in patients with moderate-to-severe plaque psoriasis, with no difference in safety signals between the two drugs. Both, however, offer distinguishable value in this treatment setting, Sorg explains, which was an important component behind Skyrizi’s launch. For people with moderate-to-severe plaque psoriasis whose disease primarily involves their skin, Skyrizi provides a well-studied safety and efficacy profile, she says. But for individuals with psoriatic arthritis whose disease involves both their skin and joints, Humira continues to be the preferred option supported by established guidelines, offering sustained skin clearance and protection against further joint damage.

“In the context of Humira, the FDA approval of Skyrizi was an opportunity to provide physicians and their patients two options with distinct mechanisms of action to meet the evolving needs and treatment expectations in psoriatic disease,” says Sorg. “As a company, we are committed to continued innovation and advancing care for people living with immune-mediated diseases like psoriasis, and the market entry of Skyrizi was the logical next chapter in our immunology portfolio expansion.”

Like most such pursuits these days, they’ve had to navigate disruptions from the COVD-19 pandemic. For Skyrizi, its momentum remains largely intact, as executives point to modest delays to new patient starts during the second quarter, but say recent Rx trends are demonstrating a strong growth trajectory, supporting AbbVie’s full-year guidance of $1.4 billion that CEO Richard Gonzalez cited in the company’s second quarter earnings call in late July.

Coverage and outlook

The wholesale acquisition cost for one dose of Skyrizi every three months is $15,842, as of January 2020. A key for AbbVie has been working with payers to ensure coverage for Skyrizi and Rinvoq—which was approved in August 2019 and could, analysts say, generate $2.2 billion in annual sales over the next four years—when most were already giving preferred status to Humira. Early on, AbbVie unveiled portfolio models such as offering discounts to payers on Humira to gain favorable formulary placement for Skyrizi and Rinvoq, the latter an oral, once-daily, selective and reversible janus kinase (JAK) inhibitor.

“We embrace the responsibility of making an impact on people’s lives by improving care for patients and ensuring access to those medicines,” says Sorg. “AbbVie worked closely with payers to secure broad and rapid formulary coverage for both Skyrizi and Rinvoq, which have positively differentiated efficacy and safety profiles compared to Humira in psoriasis and rheumatoid arthritis, respectively. Skyrizi and Rinvoq commercial access is now at parity to Humira and above 95%.”

According to comments during its 2Q20 earnings call, AbbVie is making good progress in investigating expanded uses for the two relative newcomers. For Skyrizi, the company expects to see data from Phase III studies in psoriatic arthritis later this year, and in Crohn’s disease, at the end of 2020 or early next year. Regulatory submissions for both indications are expected in 2021.

In June, AbbVie submitted applications for Rinvoq as a treatment for adults with active psoriatic arthritis and plans to file applications for two other additional indications, atopic dermatitis and ankylosing spondylitis, later this year.

Some drug launches, whether alone or in tandem, are inevitably attached with greater expectations. In AbbVie’s case, its hopes are riding on Skyrizi and Rinvoq, together, to eventually match Humira’s best year commercially and set new standards across a broad range of immunology indications.

Michael Christel is Pharm Exec’s Managing Editor. He can be reached at mchristel@mjhlifesciences.com​