In The Know: Johnson & Johnson’s Stelara faces uphill battle as the latest entry in growing universe of UC treatments

On October 21, Johnson & Johnson announced the FDA’s approval of Stelara (ustekinumab) as a therapy for adults with moderately-to-severely active ulcerative colitis (UC). According to at least one key opinion leader (KOL), Stelara’s comparable efficacy to second-line leader Entyvio (vedolizumab; Takeda), combined with an influx of new agents coming down the pipeline, could translate into limited opportunities for treatment in an already-crowded field.

Stelara is entering the market on the heels of positive two-year data from the long-term extension of the Phase III UNIFI study, which showed sustained symptomatic remission in a majority of patients. During an expert call to discuss the new drug’s approval, a leading KOL noted to FirstWord: “There is no head-to-head comparison of ustekinumab versus Entyvio or Xeljanz, but in my view ustekinumab’s efficacy is comparable to Entyvio, and less effective than Xeljanz. That's a personal view.”

How will the Stelara approval impact the UC treatment landscape?

FirstWord’s recent KOL discussion helped shed new light on current and future product positioning among an expanding universe of treatments for moderate-to-severe UC, a topic covered at length in the latest UC KOL Insight report.

As detailed in the comprehensive report, Stelara holds some key advantages in the market, mostly around safety and convenience. “The main benefit here is safety, although probably not as safe as vedolizumab,” said one KOL, adding “probably safer than the anti-TNF therapies, probably less risk of eye infection, and it doesn't appear to have a risk of lymphoma or melanoma. I think that's its big thing. Efficacy seems to be OK; obviously the Phase III trials were positive.”

Recent research shows several KOLs supported Entyvio’s position as the primary competitor to Stelara. One KOL pointed to the low rate of immunogenicity with Stelara—even lower than the already low rate found with Entyvio: “Vedolizumab is relatively low, but this seems even lower. So, the ability to use it without concomitant immune suppression is an advantage.”

However, without the data to demonstrate a fundamental advantage in terms of efficacy, patient and clinician familiarity with Entyvio is expected to continue to prevail in the market.

Stelara is also noteworthy as the first biologic treatment for UC in the EU to selectively target the IL-12/IL-23 pathway, which gives it a head start over the numerous competing companies investigating this scientific approach to treat moderate-to-severe UC. This first-to-market position cuts both ways, as the lack of clarity about the drug’s mechanism of action might also hold it back in the near term as clinicians default to more established treatment options.

Entyvio’s shift to first-line treatment option could reshuffle the deck

Stelara’s positioning as a competitor to Entyvio as a potential second or third-line therapeutic option also looms large, considering Entyvio’s move toward first-line treatment in both the US and the EU. According to KOLs interviewed by FirstWord, prospective approvals for a more convenient subcutaneous formation of Entyvio, in both pre-filled syringe and pen formats, is expected to accelerate this shift:

“I think it’s a great option to have for patients,” said one KOL, adding “there are patients who didn’t want to go on Entyvio because it was an IV, and they didn’t like that inconvenience factor. The data that I’ve seen for the sub-cu, the VISIBLE trial, looked very promising. It showed that the sub-cu formulation was basically, in terms of efficacy, equivalent to the IV formulation.”

Several KOLs cited a decrease in the use of anti-TNFs as Entyvio starts to move into this setting.

Looking at the current state of the market, Remicade (infliximab; Janssen/Merck & Co.) remains the first-choice anti-TNF among clinicians for patients with more severe ulcerative colitis. And Humira, with the relative convenience of subcutaneous injections, is still a popular first choice for more moderate sufferers. But VARSITY trial results that show superior efficacy and safety compared with the anti-TNF Humira, further strengthen the narrative of Entyvio as a sensible and safe first-line treatment.

One EU KOL also said a growing loss of response to TNF inhibitors in UC is shifting prescriptions to Entyvio: “There are an increasing number of patients who lose response to anti-TNFs. The more patients we see with anti-TNFs, the more patients must stop it because of inadequate efficacy or loss of response … In UC I think Entyvio is more effective than subcutaneous anti-TNFs.”

Unfortunately for Stelara, it appears that the treatment’s window of opportunity to grab any second-line market share from Entyvio could be fleeting for a few reasons: 1) its expensive price tag versus other treatments; and 2), the influx of new drugs in the pipeline. According to at least one KOL, other anti-IL23s will ultimately replace Stelara for Crohn’s disease; if the same happens with UC, the window of opportunity might last just a few years.

Regardless, anti-TNFs (whether originator or biosimilar) appear poised to retain a foothold in treatment of the most severe UC cases. The question that remains is: how will the growth of biologics such as IL-23 inhibitors reshape the overall treatment landscape?

Want more insight into how the increased prescribing of Takeda’s Entyvio and wider use of anti-TNF biosimilars are impacting Remicade and Humira? And the relative (if potentially short-lived) advantages for Johnson & Johnson’s Stelara?

Learn more about our latest UC KOL Insight report here, featuring US and European KOLs critically assessing 15 launched and pipeline therapies.






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