AbbVie’s Post-Humira Strategy Continues Taking Shape With Rinvoq Approval
Executive Summary
AbbVie now has both of its Humira successors approved in the US, following April’s Skyrizi approval for psoriasis. But Rinvoq faces stiff competition both within the JAK1 class and in rheumatoid arthritis generally.
AbbVie Inc. obtained its second approval in 2019 of an autoimmune therapy intended to help replace revenue from biosimilar-threatened Humira, as the US Food and Drug Administration okayed Rinvoq (upadacitinib) on 16 August to treat patients with moderately to severely active rheumatoid arthritis who have had inadequate responses to or cannot tolerate methotrexate.
The Chicago-area pharma is reportedly pricing the once-daily oral Janus kinase 1 (JAK1) inhibitor at $59,000 a year, and it hopes to launch the product by late August.
AbbVie has enjoyed a solid launch for its other new product, Skyrizi (risankizumab), which was approved to treat psoriasis in April and launched in May. It yielded $48m in sales during the second quarter, which AbbVie chairman and CEO Richard Gonzalez called “in line with expectations.” (Also see "AbbVie’s Humira Succession Plan Begins Taking Shape With Skyrizi US Approval" - Scrip, 24 Apr, 2019.) The exec said on the pharma’s second quarter earnings call that the interleukin-23 inhibitor is expected to bring in about $250m in sales this year and offers multibillion-dollar revenue potential in later years. (Also see "AbbVie’s Five Biggest Priorities, Apart From Allergan" - Scrip, 26 Jul, 2019.)
But with Rinvoq, AbbVie will need to compete in the JAK1 space with Pfizer Inc.’s market-leading JAK inhibitor Xeljanz (tofacitinib), plus an imminent challenge from Gilead Sciences Inc.’s JAK1-targeting filgotinib, as well as rheumatoid arthritis (RA) therapies in other drug classes.
AbbVie long has touted its IL-23 and JAK1 inhibitors as two prongs in its succession plan for top-seller Humira, which already faces sales erosion in Europe due to biosimilars and will face the same headwinds in the US in 2023. On the earnings call, AbbVie president Michael Severino reviewed the company’s plans to advance the two drugs into multiple indications to generate blockbuster sales.
“We believe both of our next-generation therapies have proven to be differentiated assets in their respective initial indications and have the potential to be best-in-category medicines across more than a dozen diseases,” he said. “We expect data readouts from several follow-on indications over the next 12 to 18 months, and we look forward to providing updates as these programs progress.”
Upadacitinib is in Phase III for Crohn’s disease, ulcerative colitis (UC), atopic dermatitis, psoriatic arthritis (PsA) and giant cell arteritis, while risankizumab is in Phase III in Crohn’s, UC and PsA. In a 26 July note, Morningstar analyst Damien Conover predicted that both drugs will “contribute at a more meaningful level by late 2020, as both drugs offer significant improvements over the older TNF immunology class.”
AbbVie has been playing up the potential contribution from Skyrizi and Rinvoq for years, but it also recently has taken bigger steps to get past the loss of Humira exclusivity: in late June, it announced an agreement to acquire Allergan PLC for $63bn. (Also see "AbbVie Pounces On Chance To Buy Revenues In $63bn Mega-Deal For Allergan" - Scrip, 25 Jun, 2019.)
Gilead Marching Into JAK1 Picture Quickly
AbbVie used a priority review voucher to ensure a quicker path to market for upadacitinib, but Gilead also has managed to secure a faster route to approval than expected for filgotinib.
In July, Gilead announced that it would submit filgotinib for US FDA approval in 2019, after a pre-new drug application (NDA) meeting. The agency is allowing for submission based on Gilead’s Phase III FINCH trials in RA and will accept interim data from the ongoing Phase II study MANTA to address testicular toxicity concerns. If the full data from MANTA had been required for submission, Gilead would have had to wait until 2021 to file filgotinib. (Also see "Gilead To File Filgotinib For RA in 2019, Earlier Than Forecast " - Scrip, 2 Jul, 2019.) However, filgotinib still faces the potential safety issue the MANTA studies are investigating, after lowered sperm counts were seen in animal studies.
Gilead partner Galapagos NV announced filgotinib's filing for European approval 15 August. (Also see "Europe's Biotechs Gathering Steam With Filgotinib Filing" - Scrip, 16 Aug, 2019.) Upadacitinib is under review by EU regulators.
Analysts are confident that the weight of AbbVie’s commercial machine, driven by the autoimmune disease powerhouse Humira, will keep upadacitinib competitive, but they also see that there’s a significant opportunity remaining in RA.
In a note following the European Congress of Rheumatology’s EULAR meeting in June in Madrid, Leerink analysts concluded that there was “one simple reality: the RA problem remains unsolved. Only less than 10% of patients achieve drug-free remissions despite being heavily bombarded by biologics. While the antibodies will not be disappearing anytime soon, it may be time to reconsider new modalities more broadly, increasing the opportunity for great oral drugs.”
AbbVie pointed out following the FDA approval that Rinvoq is backed by data from the 4,400-patient SELECT clinical trial program, which achieved statistically significant rates of clinical remission compared to methotrexate across several trials, as well as durable remission rates up to week 26.
Roughly 30% of patients achieved clinical remission by week 12 of treatment in the SELECT-COMPARE study and by week 14 in the SELECT-MONOTHERAPY study, compared to 6% and 8% rates for control, the company said. In SELECT-EARLY, 36% of patients receiving Rinvoq achieved clinical remission by week 12, compared to 14% who received methotrexate.
In SELECT-EARLY, 48% of patients treated with Rinvoq monotherapy achieved clinical remission at week 24, compared to 9% receiving methotrexate, while 41% receiving Rinvoq in combination with methotrexate in SELECT-COMPARE achieved clinical remission at week 26, compared to 18% in a methotrexate/placebo arm.
In addition to the original oral JAK inhibitor, Pfizer’s Xeljanz, AbbVie will have to contend with injectables like Sanofi/Regeneron Pharmaceuticals Inc.’s anti-IL-6 Kevzara (sarilumab) and tumor necrosis factor (TNF) antibodies, such as Humira, which now include biosimilars. The space continues to attract new mechanisms of action as well, like GlaxoSmithKline PLC’s anti-granulocyte macrophage colony stimulating factor (GM-CSF) otilimab (GSK3196165). (Also see "GSK's Otilimab Goes Head-To-Head To Crack Rheumatoid Arthritis" - Scrip, 4 Jul, 2019.)