“Clone or die,” read the T-shirt worn by Roche chief executive Thomas Schinecker to mark Genentech’s 50th anniversary in April – a nod to the biotech pioneer’s tradition of experimentation.Roche first bought into that culture in 1990 when it bought a majority stake, before completing a full takeover in 2009 in a $47 billion deal.The bet helped it build one of the most successful franchises in modern pharmaceuticals and become the dominant force in cancer treatment, while taking the crown as Switzerland’s most valuable listed company.But its success has waned as rivals overtake it in some of oncology’s fast-growing fields, and Roche is now trying to prove it can still produce the kind of breakthroughs that once defined it.“Roche was a standout success story and revolutionised cancer treatment,” said Beat Wittmann, founder of Swiss corporate advisory group Porta Advisors. “But it has struggled to remain a leader.”Genentech helped pioneer monoclonal antibodies, engineered proteins that target disease more precisely and turned Roche for a time into the world’s biggest cancer treatment company.“When they did that deal, antibody drugs were not trusted – then everyone followed,” said Stefan Schneider, an analyst at Vontobel.Roche’s blockbusters included Herceptin, which helped turn breast cancer into a far more treatable condition, and Avastin, approved in 2004 and one of its most successful cancer drugs.[ Irish tax payments by big US tech and pharma groups revealedOpens in new window ]The group’s oncology business grew rapidly and success became self-reinforcing, with revenues from one generation of medicines funding the next.Investors rewarded its steady growth, dependable pipeline and a long-term approach reinforced by the continued control of the 130-year-old company’s founding families.Roche has slipped down the rankings as rivals such as Merck and AstraZeneca have expanded rapidly. Photo: Rafael Henrique/SOPA Images/LightRocket/Getty But from the mid-2010s cancer treatment started moving beyond conventional antibody therapies into immunotherapies, combination treatments and targeted delivery systems – areas in which rivals moved faster.Once the world’s largest oncology company by sales, Roche has slipped down the rankings as rivals such as Merck and AstraZeneca have expanded rapidly.Merck’s Keytruda has become the world’s bestselling cancer medicine, while AstraZeneca gained ground with drugs such as Enhertu. Novartis, meanwhile, is investing heavily in radioligand therapy, another emerging form of targeted cancer treatment.Roche argues that the next era of medicine will not be built around a single breakthrough technology but around combining drugs, diagnostics and data in more personalised ways.[ How weight-loss drug Mounjaro is making Ireland the world’s fastest-growing economyOpens in new window ]Its biggest bets now include treatments designed to prevent the return of common breast cancers, obesity medicines tailored to different patients and technologies that deliver drugs more directly into the brain.As the immunotherapy arms race has intensified, Roche has pushed deeper into newer treatments and larger late-stage studies – but some of its biggest bets have failed to live up to expectations.Among Roche's biggest bets are obesity medicines tailored to different patients. Photo: Chris Radburn/PA Wire That was most visible with tiragolumab, a much-hyped cancer drug once seen as a potential successor to Merck’s Keytruda. Roche advanced the treatment into large studies after promising early data but a major 2022 lung cancer trial disappointed, as did subsequent studies.“Setbacks are an inherent part of innovation,” said Teresa Graham, head of Roche Pharmaceuticals. “Only one in every 10 clinical candidates, on average, actually makes it to market.”Further blows in breast cancer and Alzheimer’s disease also undermined confidence in Roche’s pipeline.Michael Leuchten, analyst at Jefferies, said the company’s difficulties reflected not only the scientific challenges of modern oncology but also the growing importance of the architecture of clinical studies, noting that one of Roche’s was “smaller than comparable trials run by rivals such as AstraZeneca”.[ Ireland’s EU presidency an ‘opportunity’ to safeguard pharma’s future, says industry groupOpens in new window ]“Given how crowded and competitive oncology is, you need both strong drugs and well-designed trials,” he added. “If you fall short on either, you get found out very quickly.”Schinecker has reshaped the company’s strategy since becoming chief executive in 2023. Research has been narrowed to five core therapeutic areas, while the company has adopted stricter hurdles for drug development and a more selective approach to acquisitions.You’re often only one or two major drugs away from returning to the topStefan Frings, deputy chief medical officer, described the company’s R&D overhaul as an effort to “be fast, cost-efficient and have a high rate of successful trials”.Roche, which is this week holding an investor event to promote its late-stage oncology pipeline, argues the reset is already producing results.The estimated value of its drug pipeline has risen 63 per cent since 2022 and a record number of medicines are entering late-stage development. It also remains a leader in blood cancers, while its diagnostics business provides a steady revenue stream and data to support drug development.Investors are closely watching giredestrant, an experimental breast cancer medicine that Roche believes has the potential to significantly reduce the risk of recurrence in women treated at earlier stages of the disease.[ The miracle cancer drug that saves lives but costs €8,086 per doseOpens in new window ]Although some trials have disappointed, Graham said the treatment could be the “largest-selling therapeutic in the history of Roche” if later-stage studies succeed.Part of the reset also involved looking beyond Roche’s traditional cancer stronghold for the company’s next major growth platform. Weight loss was an obvious target.Roche last year signed one of the industry’s biggest obesity deals, licensing a new treatment from Danish biotech Zealand Pharma for $5.3 billion (€4.6 billion).But early trial results disappointed investors, showing lower weight loss than rival drugs from Novo Nordisk and Eli Lilly, even if side effects appeared milder.The setback was particularly awkward because Roche had previously declined the rights to a weight-loss pill that was later acquired by Eli Lilly and is now expected to become a blockbuster after launching in April.Graham argued the market remained too focused on “shock-and-awe numbers” and said Roche believed the Zealand treatment’s tolerability could make it useful in combinations or longer-term weight maintenance.Roche is also betting heavily on a technology designed to solve one of medicine’s hardest problems.Its “Brain Shuttle” platform – “one of the biggest wild cards” according to a Roche insider – is designed to carry treatments deep into a part of the body most drugs struggle to reach.[ ‘Exciting’ advances achieved in search to reverse Alzheimer’s diseaseOpens in new window ]Early studies suggest the approach has the potential to remove almost all the protein plaques linked to Alzheimer’s disease while reducing dangerous side effects such as brain swelling. Large late-stage trials are expected to report results by 2028.Roche is also developing blood tests designed to detect Alzheimer’s earlier, potentially before severe symptoms appear.Some analysts agree Roche’s pipeline may be recovering after several difficult years. Citi wrote this year that it believed the company’s drug portfolio had “turned a corner”, while James Gordon of Barclays said the company still offered a “strong medium- to long-term growth outlook”.Jefferies’ Leuchten said Roche had become “quite good” at managing costs, with its R&D budget slightly down in 2025, but he warned that excessive discipline could also hurt innovation. “At some point you might find that you’re squeezing out the one project that might end up working.”The recovery remains a “show me” story for many investors, according to Vontobel’s Schneider, with several key drugs still needing to prove they can generate commercial success, not just promising trial results.Some also question whether Roche can recreate the kind of platform for creating blockbusters that Genentech once provided.“If you look at the biggest successes, it’s often about one or two breakthroughs,” said Christoph Wirtz, a portfolio manager at Rothschild & Co. “Roche is a very different-sized company today. Replicating something like Genentech at that scale is extremely difficult.”Yet fortunes in pharma can change quickly with the success or failure of just a handful of medicines.As one of Roche’s big US investors put it, “you’re often only one or two major drugs away from returning to the top”. – Copyright The Financial Times Limited 2026