CT-388

Roche Pharma CEO Teresa Graham spoke to Fierce Biotech on the sidelines of the company\'s first-half earnings event.\n The uncertainty around the future of Elevidys hasn’t destroyed Roche’s belief in the potential of gene therapies, the Swiss company’s head of pharma has told Fierce Biotech, as the pharma continues to expand its research reach outside of its traditional oncology focus.Roche and its partner Sarepta Therapeutics both paused trials of Elevidys back in April following the death of a 16-year-old patient in the U.S. Since then, Roche—which markets the drug outside of the U.S.—has stopped all ex-U.S. distribution of the drug in the commercial setting for non-ambulatory patients, while the FDA requested that Sarepta halt Elevidys shipments in the U.S. Earlier this week, Roche paused shipments in all patients in countries where Elevidys’ approvals referenced the FDA.But Roche Pharma CEO Teresa Graham denied Fierce’s suggestion that the issues around Elevidys have altered how the company views gene therapy as a modality.“It doesn’t, actually,” Graham told Fierce in an interview at Roche’s headquarters in Basel, Switzerland on Thursday.“The reality is that gene therapy will be an important modality in the treatment of human health,” Graham continued. “There is a lot of promise in gene therapy. I think what the entire industry is learning is that, scientifically, it\'s just a little harder than we might have thought.” Even before the latest difficulties with Elevidys, Roche had announced a “fundamental reorganization” of Spark Therapeutics, the gene therapy unit the Swiss pharma bought for $4.3 billion in 2019. That overhaul closely followed Roche’s decision to end work on a hemophilia A gene therapy candidate, which was a focus of the Spark acquisition.Roche’s move came against a backdrop of wider industry retreat from gene therapy, with Pfizer pulling its FDA-approved hemophilia B treatment Beqvez. Bluebird bio, a gene therapy pioneer once valued at $10 billion at its peak, was sold for just $49 million upfront to private equity firms.But Roche still sees potential in the modality, according to Graham.“I am firmly convicted that over time we will crack gene therapy and we will be able to deliver really meaningful treatments to patients,” she said.Graham spoke to Fierce on the sidelines of the company’s first-half earnings event, where Roche CEO Thomas Schinecker reminded journalists that 760 boys have successfully received Elevidys in the ambulatory setting.“I\'m really hopeful that we can find a path forward for this medicine,” Graham said in the interview on Thursday. “We clearly need to talk to regulators; we clearly need to have some good conversations about the safety—but we do firmly believe in the risk-benefit of this product.”Not all regulators sound ready to be convinced, with the European Medicines Agency (EMA) announcing Friday morning that it won\'t recommend Elevidys for approval in the ambulatory setting. Roche said in a statement that it “plans to continue to work with the EMA to explore a potential path forward.” Mixed results from emerging pipeline Another drug that Roche is keeping faith in is the Parkinson’s disease prospect prasinezumab. The future of the Prothena Biosciences–partnered asset looked in doubt after the anti-alpha-synuclein antibody failed a phase 2 study in December 2024.But Roche is giving prasinezumab a second chance, with plans to launch a phase 3 trial by the end of the year off the back of an analysis of data from the failed study. Specifically, the pharma pointed to longer-term follow-up data from an open-label portion of the study suggesting a clinical benefit on top of symptomatic treatment in early-stage Parkinson’s.“Given the dramatic unmet need in Parkinson\'s, it does feel like it would be a miss not to explore this,” Graham explained.“There\'s only really been minor improvements in treatments for these patients over the last 50 years, and, in every conversation I\'ve had with [key opinion leaders], they have really encouraged us to take this forward,” she said.“There\'s a little bit of a finger feel that there\'s something there, and we\'re only really ever going to be able to pull the signal out in a phase 3,” Graham added. Roche had less faith in CT-173, an early-stage obesity drug picked up as part of its $2.7 billion acquisition of Carmot Therapeutics in 2023. The Swiss pharma had previously touted the long-acting PYY analog’s potential to drive weight loss past the GLP-1 plateau, but Graham announced at the earnings event that Roche would no longer take CT-173 into human trials after assessing its “developability and competitiveness.”Despite this early-stage setback, Graham still feels that combinations offer Roche a path to carving out its own corner of the increasingly crowded obesity space.“Obesity is inherent in something like 200 other diseases,” she said. “So the ability to actually look at where we believe our portfolio in combination with other drugs can really help address some of these comorbidities is one of the more exciting pieces.”“This is an incredibly big market,” Graham added. “It is very diverse. There are a lot of scientific pathways to explore here.”One of those pathways is amylin, a hormone involved in the regulation of food intake. In March, Roche paid Zealand Pharma $1.6 billion for the long-acting amylin analog petrelintide. Graham sees the drug’s potential growing as the obesity market segments among patients “looking for maybe different depths of weight loss or different tolerability profiles.”Meanwhile, Roche has yet to make a final call on whether to take the GLP-1/GIP receptor agonist CT-388—another Carmot asset—into a phase 3 obesity trial, but Graham said the company is “right on the cusp” of taking that program forward.“We plan to make those decisions later this year, and, once we get rolling here, I think you\'re really going to see us flesh out our [obesity] strategy,” she said. When it comes to bringing new drugs into Roche’s pipeline, Graham was tight-lipped on which of the company’s five core focus areas—neurology, oncology/hematology, immunology, ophthalmology and CVRM (cardiovascular renal metabolic)—the company is prioritizing for M&A.“Clearly, within our five therapeutic areas, there are definitely places where we would like to bring in additional assets,” she told Fierce. “As Thomas [Schinecker] said, we look at an unbelievably large number of deals every year, and are constantly on the hunt, not only for things that will fit that strategy but things that are truly transformational.”With such a multifaceted pipeline, what are the readouts Graham is most excited about?“It\'s like trying to choose your favorite child,” she said, before name-checking the recent “super exciting” phase 2 results for the BTK inhibitor fenebrutinib in relapsing multiple sclerosis (MS). “It could be a really huge step forward for MS patients,” she explained.There’s also the “high-risk, high-reward bet” on the Parkinson’s drug prasinezumab, said Graham, who ended by referencing the IgG1 monoclonal antibody afimkibart.Along with CT-388 and the Alzheimer’s disease prospect trontinemab, afimkibart was one of the assets Roche fast-tracked as part of its reallocation of R&D resources.“I\'m an immunology girl at heart—it’s where I started my career,” Graham explained. “There\'s so much opportunity in the immunological space and so many diseases that we could potentially tackle with afimki.”

iStock, Prostock-Studio R&D spending across the global pharmaceutical sector climbed 1.5% in 2024, according to unreleased data from Evaluate Pharma. Even with strong macro headwinds —inflation, rising costs, geopolitical tensions —the global pharmaceuticals industry continued to pump more money into R&D investments in 2024. That’s according to data from analyst firm Evaluate Pharma, which in an email gave BioSpace a sneak peek at their World Preview 2025 report, set to be published in June 2025. Pharma R&D spending in 2024 grew by 1.5%, a relatively modest jump by the industry’s own standards, considering that from 2022 to 2023, budgets soared 11.5%. Still, R&D spending last year was staggering: drugmakers the world over pumped nearly $288 billion into research and development. “R&D is central to refreshing product portfolios, which have a natural lifecycle owing to patents and exclusivity periods,” Daniel Chancellor, VP of thought leadership at Norstella, Evaluate’s parent company, told BioSpace . “Without reinvestment into R&D (or business development), revenues are increasingly at risk of competition and will inevitably decline.” This is why Evaluate estimates that the industry will continue to grow their R&D budgets through the end of the decade—which, as per its yet-to-be-released data, could reach just under $340 billion by 2030—even as the political and economic environment grows increasingly unwelcoming. “R&D spending will continue to grow, thankfully because industry revenue growth is robust,” Chancellor assured BioSpace . He qualified this assertion, however, by noting that Evaluate “expects R&D margins to decline” as companies continue to enact “cost containment measures” to surmount the increasing number of external challenges to their businesses. These challenges include tariffs, drug pricing and the cost of capital. In the context of these high-level barriers, Guglielmo Bruni Roccia, senior pharmaceutical industry analyst at BMI, a Fitch Solutions company, offered a more pessimistic view of R&D spending patterns in the coming years. President Donald Trump’s Most Favored Nation drug pricing policy , for example, “could result in compression of U.S. revenues, which would in turn reduce available R&D funding,” Roccia told BioSpace . “With constrained revenue streams, we expect pharmaceutical companies will likely prioritize R&D projects with greater certainty of profitability and where they have a greater competitive advantage,” he added. Still, there is reason to be optimistic. Experts who spoke with BioSpace pointed to the industry’s spending spree, particularly in manufacturing , as a promising signal. “Infrastructure investments enhance R&D capabilities, indicating a complementary rather than competitive relationship,” Roccia explained, noting that a manufacturing push “will support and potentially boost R&D activities rather than hinder them.” Norstella’s Chancellor agreed, adding that “these new facilities will rely on the success of R&D to produce the drugs of tomorrow, as well as meeting demand for current portfolios.” Dealmaking appears to be continuing at pace, as well. Despite an increasingly tricky political thicket , the first quarter witnessed a rush of M&A and licensing deals, with the industry earmarking some $40 billion for business development initiatives. This bodes well for the industry, since deals contributed heavily to the encouraging R&D trend in 2024. All top spenders in this list are anchored by a major contract at least hundreds of millions of dollars in value, bolstered by additional spending to beef up their pipelines. Below, BioSpace looks at the pharma industry’s most prolific investors in R&D and how they are using these budgets to advance their business. Merck Reigns Even After Scaling Back R&D Spend: $17.9 billion YoY Change: -41% In 2023, Merck went on an expensive deal-making spree. The pharma acquired immune specialist Prometheus Biosciences for $10.8 billion , licensed three of Daiichi Sankyo’s antibody-drug conjugates for $4 billion upfront and inked a potential $2.55 billion molecular glue deal with Proxygen, among other transactions. With a particularly bloated R&D purse in 2023, the 41% decrease in spending last year is more of a rightsizing of Merck’s budget than a steep scale-back. Indeed, the company still came out ahead of its Big Pharma peers with a hefty $17.94 billion investment, corresponding to 28% of its total revenue. “With the looming loss of exclusivity of Merck’s Keytruda, Merck has ramped up R&D efforts to address the nearly $30 billion revenue gap left by the drug,” Ophelia Chan, senior business fundamentals analyst at GlobalData, told BioSpace. “It’s worth keeping a close eye on [Merck’s] pipeline, which includes around 20 potential new blockbuster candidates that could collectively generate over $50 billion in the future,” Chan added. Among them is ifinatamab deruxtecan, an antibody-drug conjugate (ADC) that targets B7-H3, a transmembrane protein over expressed in various cancers. Merck is running the Phase III IDeate-Esophageal01 study to test the ADC in advanced or metastatic esophageal squamous cell carcinoma. Ifinatamab deruxtecan is also being proposed for heavily pretreated advanced small cell lung cancer, for which it is in late-stage development . Merck is also testing tulisokibart (MK-7240), which was picked up in the $10.8 billion acquisition of Prometheus Biosciences, in multiple inflammatory diseases . Phase II data, published in the New England Journal of Medicine in September 2024, showed that a higher percentage of ulcerative colitis patients treated with the anti-TL1A antibody achieved clinical remission versus placebo. Tulisokibart is in Phase III development for ulcerative colitis and Crohn’s disease. Merck CEO Robert Davis told investors in February that he expects blockbuster opportunities from the pharma’s ophthalmology business, which received a $1.3 billion boost last year with the May acquisition of the eye specialist EyeBio. The centerpiece of the acquisition is the trispecific antibody Restoret being assessed for diabetic macular edema (DME) and neovascular age-related macular degeneration (AMD). In September 2024, Merck kicked off the Phase IIb/III trial for Restoret in DME. The study, dubbed BRUNELLO , is set to complete by the end of 2027. Johnson & Johnson Strong in Cancer and Immuno—but not Neuro R&D Spend: $17.2 billion YoY Change: 14.2% J&J started 2024 by renewing its focus on its three main priority therapeutic areas—“oncology, immunology and neuroscience,” CEO Joaquin Duato told investors during the pharma’s full-year 2023 earning call—and the pharma’s R&D spending last year largely reflected this. For instance, J&J paid $2 billion to acquire Ambrx in January 2024. The bet builds out the pharma’s portfolio of ADCs, which in recent years have become a major focus in cancer therapy. In addition, J&J last year made two hefty investments into its immuno business: the $850 million acquisition of Proteologix and its pipeline of anti-inflammatory dermatology assets, and a $1.25 billion payment to Numab Therapeutics for its bispecific antibody for atopic dermatitis. All told, J&J spent more than $17.2 billion on R&D last year, accounting for over 19% of its total revenue. This sum also covers its medtech investments. Even as these deals helped J&J populate its early- and mid-stage pipelines, the pharma last year likewise pushed its late-stage assets forward. In immuno, for instance, the company in August 2024 sought approval for its monoclonal antibody nipocalimab in myasthenia gravis, which was ultimately granted in April to be marketed as Imaavy. Notably, neuroscience was a weak point for J&J’s 2024 R&D agenda. In October 2024, the pharma pruned its early- and mid-stage neuro pipeline, leaving the investigational human orexin-2 receptor blocker seltorexant on the cutting room floor. J&J had been studying seltorexant for agitation and aggression in Alzheimer’s disease. The company also axed a Phase II ion channel blocker for bipolar depression and a Phase I Parkinson’s disease therapy. J&J seems set on changing that this year, however, starting 2025 strong with the massive $14.6 billion acquisition of Intra-Cellular Therapies. Roche’s Mixed Year for Cancer R&D Spend: CHF 13 billion ($15.8 billion) YoY Change: 1% During its full-year 2024 business report in February 2024, Roche leaders recognized that sales were stagnating, driven largely by tanking demand for its COVID-19 products and currency difficulties at the time. The company identified dealmaking as one of its care strategies to revitalize growth. Still, unlike Merck and J&J, which enacted substantial changes to their budgets, Roche’s R&D spending in 2024 remained largely flat year-on-year. The Swiss company poured just over CHF 13 billion ($15.8 billion) in its R&D and business development efforts last year, a slight 1% increase from 2023. 2024 also posed formidable challenges to Roche’s R&D efforts in cancer. In July 2024, for instance, the company’s anti-TIGIT antibody tiragolumab failed to significantly improve progression-free survival in the Phase II/III SKYSCRAPER-06 study in NSCLC, forcing Roche to discontinue that trial. A few months later, in November, tiragolumab again delivered disappointing NSCLC outcomes . Perhaps reflecting these difficulties in oncology development, Roche in April 2024 axed three early-stage cancer assets, including camonsertinib, which it was testing for solid tumors. In August, Roche closed down the cancer immunology unit of its subsidiary Genentech, with a spokesperson at the time pointing to “shifts in the science of immuno-oncology” as the reason for the shake-up. Despite some obstructions in oncology, Roche in 2024 saw notable progress in its obesity portfolio, anchored by the assets it obtained from its $2.7 billion acquisition of Carmot Therapeutics in December 2023. Last May, the pharma announced that Carmot’s CT-388, a dual GLP-1/GIP receptor agonist, could lower bodyweight by 18.8% versus placebo at 24 weeks. Roche followed this up with a July 2024 readout for another Carmot asset, the oral GLP-1 receptor agonist CT-996. Phase I data at the time showed that the pill can cut weight by 6.1% versus placebo after four weeks. Roche’s standout deal last year was the November 2024 acquisition of Poseida Therapeutics for $1 billion upfront. Roche and Poseida are long-time partners , and the acquisition strengthens their CAR T collaboration, targeting multiple myeloma and B cell lymphomas, among other blood cancers. With more than half of the year left to go, it remains unclear how Roche’s R&D budget will change in 2025—though it’s unlikely that the pharma will go on a big spending spree soon. During its full-year business report in February, CEO Thomas Schinecker said that Roche will remain “ disciplined ” with dealmaking this year, focusing only on assets that make strong financial sense for the company. AstraZeneca Upped Investment to Buff Pipeline R&D Spend: $13.6 billion YoY Change: 25% AstraZeneca opened 2024 with a commitment to “investing in new technologies and new products to shape the future of medicine,” CEO Pascal Soriot said in February 2024 during the pharma’s full-year 2023 earnings call. A month later, in March, AstraZeneca made good on this commitment by inking two high-ticket acquisitions to build out its late-stage pipeline. The first of these deals is with Amolyt Pharma, which the pharma acquired for $800 million upfront . A few days later, AstraZeneca dropped $2 billion to acquire Fusion Pharmaceuticals. From Amolyt, AstraZeneca received the hypoparathyroidism candidate eneboparatide, which recently aced a Phase III trial , along with other assets being developed for rare diseases. Meanwhile, Fusion gave AstraZeneca its radiopharma pipeline, anchored by FPI-2265, an actinium-225 radioconjugate therapy being proposed for the treatment of metastatic castration-resistant prostate cancer. AstraZeneca last year also poured money into the opposite end of its pipeline, expanding its early-stage portfolio with a $19 million deal with Nona Biosciences in May 2024 for several preclinical monoclonal antibodies for cancer. That same month, AstraZeneca started putting bets in the lucrative obesity arena by paying $80 million to support Versant Ventures startup SixPeaks, which will work on next-generation, muscle-preserving weight-loss drugs. One of AstraZeneca’s most closely watched assets is its Daiichi Sankyo-partnered antibody-drug conjugate Dato-DXd. Despite winning FDA approval earlier this year for breast cancer under the brand name Datroway, the molecule ran into a rough patch last year, failing two Phase III trials in September—one in breast cancer and another in non-small cell lung cancer . Elsewhere in AstraZeneca’s cancer pipeline, the AKT blocker Truqap in November 2024 delivered a late-stage victory , significantly improving radiographic progression-free survival in certain types of prostate cancer. In April, however, Truqap stumbled in a Phase III prostate cancer, pushing the pharma to axe the Phase III CAPItell-280 study. AstraZeneca appears to be sustaining the pace of its R&D spending into the new year. In March alone, for instance, the pharma put $1 billion on the line to acquire EsoBiotec and its cell therapy pipeline, and signed two agreements with South Korea’s Alteogen to collaborate on subcutaneous cancer therapies. All told, AstraZeneca’s payments to Alteogen could total $1.35 billion . AbbVie Makes Strong Neuro Push R&D Spend: $12.8 billion YoY Change: 60% Of all the companies on this list, AbbVie saw the biggest increase in its R&D spending, soaring 60% year-on-year to hit nearly $12.8 billion. Likely the biggest contributing factor is the pharma’s $8.7 billion acquisition of Cerevel Therapeutics in December 2023. The star of this buyout was the next-generation antipsychotic agent emraclidine, which ultimately failed a pair of Phase II trials, forcing investors to question AbbVie’s neuro strategy. The Cerevel acquisition wasn’t a complete wash for AbbVie, however. In September 2024, just a month after closing the transaction, the pharma notched a late-stage clinical win in Parkinson’s disease with tavapadon. Beyond Cerevel, AbbVie sustained its neuro push in 2024, linking up with Gilgamesh Pharmaceuticals in May 2024 for $65 million upfront and up to $1.95 billion in option and milestone fees. The partnership is focused on developing psychedelic therapies for psychiatric indications. Outside of neuro, AbbVie in 2024 leaned further into its main area of expertise—immunology —putting up $250 million to acquire Massachusetts biotech Celsius Therapeutics and its investigational antibody for inflammatory bowel diseases. Oncology also saw a lot of progress for AbbVie last year, including a slew of positive readouts in ovarian cancer, non-small cell lung cancer and other solid tumors at ESMO 2024. A few months later, in December, the pharma likewise released data supporting the use of its bispecific T cell–engaging antibody epcoritamab as a monotherapy or as part of a combination regimen in patients with diffuse large B cell lymphoma. Despite being among pharma’s top R&D spenders, AbbVie doesn’t seem to be resting on its laurels. Already, the company has made several deals this year that could top $1 billion. In January, AbbVie teamed up with Neomorph to develop molecular glue degraders, putting up to $1.64 billion on the line for this partnership.