Biosimilar treatments for inflammatory bowel disease have been available in Europe for a number of years.
Indeed, more than a decade after biosimilars to Remicade (infliximab) were approved, followed several years later by biosimilar Humira (adalimumab), these are firmly entrenched in the European market, with penetration rates of 80% and beyond in some of the EU5 markets; and up to 99% in Nordic markets like Norway and Denmark.
Infliximab and adalimumab have also reached the US, although they notoriously struggled to capture share in their early time on the market compared to oncology monoclonal antibodies like trastuzumab and bevacizumab. (Also see "Generics Bulletin Explains: After Humira Biosimilars, Will It Be Groundhog Day For Stelara?" - Generics Bulletin, 15 July, 2024.)
In recent days, new ground has been broken in the IBD space – the debilitating Crohn’s disease and ulcerative colitis – with the approvals and launches of biosimilars to Johnson & Johnson’s Stelara (ustekinumab) at the end of July.
While infliximab and adalimumab paved the way for biosimilar anti-tumor necrosis factor (anti-TNF) therapies, ustekinumab is the first biosimilar targeting interleukin (IL)-12 and IL-23 cytokines, which are also known to play a key role in inflammatory and immune responses.
Stelara carries an indication for both Crohn’s disease and ulcerative colitis – albeit for patients that have not improved enough with other treatments or who cannot receive such treatments.
Stada and Alvotech’s Uzpruvo and Sandoz and Samsung Bioepis’ Pyzchiva ustekinumab biosimilars launched in Europe within several days of each other, both containing indications for Crohn’s disease. (Also see "Second European Stelara Biosimilar Pits Sandoz Against Stada" - Generics Bulletin, 25 July, 2024.)
However, neither biosimilar is indicated for ulcerative colitis as J&J holds exclusivity for that indication, which it received in Europe only in 2019.
According to Leerink Partners, roughly 75% of Stelara’s near $11bn global sales come from its inflammatory bowel disease indications. Such a lucrative market has naturally attracted further development of biologics; and with this, of course, the development of competing biosimilars.
With biosimilars to ustekinumab now competing for share for one IBD indication at least in Europe, while also set to reach the US at the beginning of 2025, Generics Bulletin reviews the current state of biosimilar development for IBD biologics.
Simponi/Simponi Aria (golimumab)
Development of biosimilars to another of Johnson & Johnson’s IBD biologics is well underway, though it should be noted that golimumab is indicated to treat ulcerative colitis only with certain stipulations, including when certain other UC medicines have not worked well enough or cannot be tolerated.
Alvotech has pointed to a distinct lack of other rivals in the market for golimumab biosimilars, as the firm recently delivered positive topline results for its AVT05 candidate in patients with moderate to severe rheumatoid arthritis. (Also see "Alvotech Highlights Lack Of Simponi Rivals As It Delivers Golimumab Results" - Generics Bulletin, 24 April, 2024.)
Shortly thereafter, Stada shook hands with Bio-Thera Solutions on an exclusive commercialization and license agreement for the Chinese firm’s BAT2506 proposed biosimilar to Simponi the EU, the UK, Switzerland and select other countries. (Also see "Bio-Thera And Stada Joins Forces On Golimumab, With Up To $160m On The Table" - Generics Bulletin, 29 May, 2024.)
“With global sales in 2023 of US$2.2bn, including more than US$1bn outside of the US, golimumab represents a compelling opportunity to broaden patient access to biological treatments,” commented Stada’s head of Global Specialty, Bryan Kim.
Tysabri (natalizumab)
Sandoz earlier this year debuted competition to Biogen’s Tysabri – but given the significant limitations for its IBD indication, barely mentioned it, instead welcoming its Tyruko biosimilar as the “first and only biosimilar for multiple sclerosis.” (Also see "Sandoz Reveals European Natalizumab Launch Amid GLP-1 Ambitions" - Generics Bulletin, 11 January, 2024.)
Tysabri is approved for Crohn’s disease, but only for inducing and maintaining clinical response and remission in adult patients with condition; and these patients only with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional therapies and TNF-alpha inhibitors.
Meanwhile, Tysabri carries well-known safety concerns. It may not be appropriate for people who have weakened immune systems or who have ever had the John Cunningham virus, which if so, could trigger progressive multifocal leukoencephalopathy, a rare but serious, and often fatal, infection of the brain.
Entyvio (vedolizumab)
Takeda’s α4β7 inhibitor Entyvio has been called “the biologic of choice for IBD,” and upon launch became the first biologic therapy specifically designed for a gastroenterological indication.
Bringing in sales of ¥800bn ($5.2bn) in Takeda’s financial year to March 2024, Entyvio sales are anticipated by the Japanese originator to peak at between $7.5bn and $9bn by the end of the decade.
With such a large target, biosimilar developers naturally are circling. “The first vedolizumab biosimilar Phase III study, from Polpharma Biologics, has an estimated primary completion in September 2025,” Cowen Research notes. (Also see "Polpharma Biologics CEO Discusses Natalizumab Milestone" - Generics Bulletin, 10 August, 2023.)
In February this year, Polpharma Biologics announced topline results demonstrating the pharmacokinetic and pharmacodynamics comparability of its PB016 vedolizumab biosimilar candidate to Entyvio.
Moreover, pureplay biosimilar developer Alvotech has a biosimilar Entyvio candidate in its pipeline, AVT16. Last year, the Icelandic firm forged a partnership with Advanz Pharma for its proposed biosimilar to Entyvio, as well as its Simponi biosimilar candidate. (Also see "Alvotech Makes Multiple Moves As It Allies With Advanz For Five European Biosimilars" - Generics Bulletin, 24 May, 2023.)
“We are not speaking enough about this candidate,” Alvotech’s management told investors in June. “We are going to be one of the two companies starting the clinical trials. This is also another asset partnered with Teva in the US market and different partners in Europe and Japan.”
Takeda has in recent years expressed that it is “highly unlikely that we will see a biosimilar launch this decade, and it could be as late as 2032” – despite anticipated data exclusivity expiries in the EU in May 2025 and the US in May 2026. (Also see "Takeda Feels Confident Of No Entyvio Biosimilars Until Early 2030s" - Generics Bulletin, 2 November, 2022.)
Entyvio, it observes, “is only approved in inflammatory bowel disease indications, for which clinical trials are typically longer and more challenging to complete than other autoimmune diseases that we have recently observed biosimilar manufacturers target.”
Asked in March this year about the onset of biosimilar Phase III clinical trials, Takeda’s management said there was “nothing new that has changed our outlook.”
Cimzia (certolizumab pegol)
UCB’s Cimzia (certolizumab pegol), a roughly €2bn ($2.2bn) TNF inhibitor, carries an indication for reducing signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.
Among known chasers are Sweden’s Xbrane Biopharma, which has partnered with multinational powerhouse Biogen for the firms’ BIIB801 candidate.
Recently, Xbrane produced the first drug substance scale-up batch with the firm’s contract manufacturer ahead of plans to produce good manufacturing practice batches during the end of 2024 and beginning of 2025. (Also see "Xbrane Inching Closer To Cimzia Biosimilar Trials With Batch Production" - Generics Bulletin, 17 July, 2024.)
Xbrane says it expects to be able to sell the drug substance from the scale-up batches to its commercial partner Biogen; and to have finalized its development responsibilities of the program by mid-2025.
At that point, Biogen will take over the responsibility for further development, including clinical and regulatory development, on the path towards a potential marketing authorization.
UCB commented a year ago: “What we’re understanding right now is that there’s a single agent that is about to start the early clinical work. And so, therefore, we don’t see an approval of a Cimzia biosimilar in the first markets worldwide before the end of 2026.”
“I think Cimzia was a good choice of product from us,” Xbrane CEO Martin Åmark told Generics Bulletin recently as part of an exclusive interview. (Also see "‘Keytruda? We Believe Opdivo Is The Better Choice’: Xbrane’s CEO Martin Åmark" - Generics Bulletin, 11 June, 2024.)
“It’s a €2bn drug, it has a niche position in breastfeeding and pregnant women, and I think it seems to be holding its position despite biosimilars on the other TNFs.”
“Also,” Åmark noted, “it’s expressed in e coli, which is really our stronghold from a yield production cost perspective. And the difficulty in doing a biosimilar here is to really to get the yield up to a level that makes it commercially viable from a production cost perspective.”
