OSAKA, Japan—The immunosupressive TNF blocking agent Humira (adalimumab) from AbbVie can treat arthritis, plaque psoriasis, ankylosing spondylitis, Crohn's disease and ulcerative colitis. But it looks like it may be getting some stiff competition—at least in the gut—from another biologic drug.
Specifically, Takeda Pharmaceutical Co. Ltd. has announced results from the Phase 3b head-to-head VARSITY study, which reportedly demonstrated that the gut-selective biologic vedolizumab (Entyvio) was superior to the anti-tumor necrosis factor-alpha (anti-TNFα) biologic Humira in achieving clinical remission in patients with moderately to severely active ulcerative colitis at week 52.
“As the first clinical study to directly compare the efficacy and safety of two commonly used biologic therapies in patients with ulcerative colitis, VARSITY provides invaluable knowledge to help inform physicians’ treatment decisions when initiating biologic therapy,” said Dr. Jeff Bornstein, executive medical director for Takeda. “This is also the first time we have seen a direct comparison between two medicines with distinct modes of action in ulcerative colitis: the gut-selective anti-alpha4beta7 integrin vedolizumab and the anti-TNFα adalimumab. This is an exciting time in the landscape of ulcerative colitis treatment, as head-to-head clinical data has not previously been available to guide treatment decisions around biologic therapies.”
Data showed that 31.3 percent (n=120/383) of patients receiving vedolizumab intravenous (IV) achieved the primary endpoint of clinical remission, compared to 22.5 percent (n=87/386) of patients treated with adalimumab subcutaneous (SC) at week 52, with the difference being statistically significant (p=0.0061). These results were announced at an oral presentation on March 9 at the 14th Congress of the European Crohn’s and Colitis Organisation in Copenhagen, Denmark.
Takeda also says that treatment with vedolizumab was associated with significantly higher rates of mucosal healing at week 52, with 39.7 percent of patients who received vedolizumab achieving mucosal healing compared to 27.7 percent treated with adalimumab (p=0.0005). A non-statistically significant difference in favor of adalimumab was seen in the percentage of patients using oral corticosteroids at baseline who discontinued corticosteroids and were in clinical remission at week 52.
The study was not powered to compare the safety of the two biologics; nonetheless, Takeda pointed out that patients treated with vedolizumab (62.7 percent) had a lower rate of overall adverse events over 52 weeks than patients treated with adalimumab (69.2 percent), with a lower rate of infections reported in patients treated with vedolizumab (33.5 percent) as compared to adalimumab (43.5 percent). The rate of serious adverse events was also lower in vedolizumab-treated patients than adalimumab (11.0 percent vs. 13.7 percent respectively).
“The VARSITY study addresses critical questions concerning the selection of biologic therapy in ulcerative colitis,” remarked Dr. Bruce E. Sands, primary investigator of the VARSITY study and chief of the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai Hospital and the Icahn School of Medicine at Mount Sinai. “The goal of treatment in ulcerative colitis is to achieve clinical remission and mucosal healing, and these results clearly highlight the benefits seen with vedolizumab versus adalimumab on these important outcomes. The results also showed lower rates of overall and serious adverse events including infections in patients treated with vedolizumab than adalimumab.”
VARSITY is a Phase 3b, randomized, double-blind, double-dummy, multi-center, active-controlled study to evaluate the efficacy and safety of vedolizumab IV compared to adalimumab SC at week 52 in patients with moderately to severely active ulcerative colitis. The study randomized 769 patients (vedolizumab n=383 or adalimumab n=386), all of whom had inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators or one TNFα-antagonist other than adalimumab prior to being enrolled.
Despite the competition, Humira still seems to have plenty of legs right now for staying in the race for market share. As analyst firm GlobalData notes, AbbVie and Eisai announced recently (just a couple days before the Takeda presentation noted above, in fact) that Humira had received additional approval for the treatment of hidradenitis suppurativa (HS) in Japan. This will strengthen AbbVie’s profits even though there is increasing competition from Humira biosimilars, according to GlobalData.
Currently, there are limited biological therapies for HS, a chronic inflammatory skin condition that is characterized by the development of abscesses and scaring on the skin. At present, Humira is the only approved biologic for HS in the United States and European Union. With the additional approval, it becomes the first-to-market biological treatment indicated for HS in Japan and is now approved for 11 indications in that country.
“AbbVie has continued with its trend of being the first company to launch Humira for HS in a market, as it did in the US and EU. However, the company faces an imminent threat from increasing shares of biosimilar adalimumab, which launched in the EU in 2018,” noted Dr. Vikesh Devlia, a pharma analyst at GlobalData. “Nevertheless, the approval of Humira in Japan shows that AbbVie strives to increase its global market share while also increasing the number of indications it can treat with this biologic. In 2018, the company reported that Humira generated global sales of $19.9 billion, an 8.2-percent increase compared to 2017 … GlobalData anticipates the sales of Humira to continue to increase in 2019 despite direct competition from biosimilars, and the latest approval for HS in Japan will bolster AbbVie’s profits further.”