SGLT2

Enhanced tax incentives or an extension of the U.S. Tax Cuts and Jobs Act make “better tools” to spur U.S. growth than import tariffs do, Eli Lilly CEO Dave Ricks said. As multiple large drugmakers look to navigate trade turbulence by pumping billions of dollars into their U.S. operations, a growing number of biopharma leaders are speaking out against the Trump administration’s tariff agenda.Take Eli Lilly helmsman Dave Ricks, for example. Despite the Indianapolis pharma making a $27 billion U.S. production pledge in late February, Ricks took his company’s first-quarter earnings call Thursday to argue against trade levies as the best policy for supporting local industry. “We support the U.S. government’s goals to increase domestic investment,” the CEO said on the call. “However, we don’t believe tariffs are the right mechanism.”Rather, “enhanced” tax incentives—or an extension of the Tax Cuts and Jobs Act—are “better tools” to spur U.S. growth, Ricks contended. The President Donald Trump-led Republican Party ushered in the Tax Cuts and Jobs Act in 2017, slashing the U.S. corporate tax rate from 35% to 21%, among many other measures. Now, as the threat of sector-specific tariffs on pharmaceuticals dominates the industry’s attention, multiple biopharma leaders have been advocating for tax reform—rather than trade duties—as a preferable route to bolster U.S. manufacturing and investments.Notably, Johnson & Johnson CEO Joaquin Duato and AbbVie Chief Financial Officer Scott Reents also used their company’s recent earnings calls to argue in favor of more competitive tax policies—and caution against the potential harm tariffs may inflict.A big part of Trump’s goal with his tariffs—both imposed and threatened—is to spur a return to U.S.-based manufacturing. On that front, Lilly, like many others in the pharma industry, appears willing to play ball.In late February, the drugmaker said it would invest $27 billion and start construction this year on four new U.S. manufacturing facilities. Once completed, the effort should equip Lilly to make all its medicines for the U.S. market in the U.S., Ricks said on Thursday’s call.In summarizing his thoughts, the CEO urged the second Trump administration to “negotiate deals with key trading partners as soon as possible, then level the playing field for American exporters like Lilly and remove harmful tariffs and non-tariff market access barriers in the developed economies.”The CEO’s comments came as Lilly posted a 45% year-over-year revenue increase to $12.73 billion in 2025’s first quarter. Unsurprisingly, much of that growth can be attributed to the Indianapolis drugmaker's star GIP/GLP-1 blockbusters Mounjaro and Zepbound, the company explained in an earnings release.Mounjaro, approved in Type 2 diabetes, raked in $3.8 billion for the period, growing a staggering 113% over the $1.8 billion it brought home during 2024’s first quarter. Mounjaro’s obesity counterpart Zepbound generated $2.3 billion in the quarter, compared with $517 million during the first three months of the previous year. The FDA approved Zepbound in November 2023.Lilly also noted that its breast cancer med Verzenio grew sales 10% to $1.2 billion in the first quarter, while the company’s SGLT2 inhibitor Jardiance benefited from a one-off $370 million gain after Lilly and Boehringer Ingelheim tweaked their commercialization pact for the drug.Still, even drugs like Mounjaro and Zepbound can stumble.Following talks with the FDA, Lilly has withdrawn its application for tirzepatide—the molecule underpinning both Mounjaro and Zepbound—in heart failure with preserved ejection fraction (HFpEF), the company’s chief scientist, Dan Skovronsky, M.D., Ph.D., said on Lilly’s call.While the company feels the phase 3 data from its Summit trial merit an approval in the indication, the FDA communicated that it would need an additional confirmatory clinical trial to move forward, Skovronsky explained.Last August, Lilly reported data from the Summit study that showed tirzepatide reduced the risk of adverse HF outcomes like hospitalization or cardiovascular death by 38% compared to placebo. The study tested Lilly’s dual GIP/GLP-1 receptor agonist against placebo in 731 patients with HFpEF and obesity.A peptide drug stumbling in the HFpEF indication isn’t unique to Lilly: Last Summer, Novo Nordisk pulled its heart failure application for Wegovy—Zepbound’s chief rival in obesity—and telegraphed plans to resubmit its filing in early 2025.Because Novo’s studies in the indication were “reasonably small,” the FDA wanted to see an increase in number of total cardio events to validate Wegovy’s effect, Novo development chief Martin Holst Lange, M.D., Ph.D., said at the time. Novo subsequently resubmitted its application in January with additional data, a company spokesperson confirmed.  Looking forward at the rest of the year, Lilly is sticking by the 2025 revenue guidance it’s previously communicated. The company currently expects to generate sales between $58 billion and $61 billion for the full year. The company caveated that its financial expectations are based on the “existing trade environment as of May 1, 2025.” The forecast does not account for any policy shifts, including potential pharmaceutical-specific import tariffs, Lilly said. 

One of Novartis’ most important clinical catalysts of the year came Thursday, with the accelerated approval in the US of its rare kidney disease drug. Atrasentan, which is now named Vanrafia, is a once-daily pill that may be used to treat protein accumulation in patients with primary IgA nephropathy (IgAN). Specifically, the drug may be used in patients at risk of rapid disease progression, which is generally defined using the urine protein-to-creatinine ratio, according to a release . The drug can be added on top of supportive care, such as the widely used renin-angiotensin system inhibitors, with or without the kidney disease meds known as SGLT2 inhibitors. Novartis has not yet disclosed the list price for Vanrafia. IgAN is a chronic disease that occurs when abnormal antibodies build up in the kidney’s tiny filters, which can damage the organ. Some people who have IgAN eventually require dialysis or a transplant. Importantly, the FDA did not require a risk evaluation mitigation strategy (REMS) program for Vanrafia. But patients must have their liver enzyme levels tested before and during treatment “when clinically indicated,” according to Novartis, as some similar drugs have been linked with increases in aminotransferases, hepatotoxicity and liver failure. The company also warned that Vanrafia may cause serious birth defects. Unlike Travere Therapeutics’ Filspari, which won full approval last year for the disease, Vanrafia is not subject to a drug safety program, or REMS. Filspari is only available via a REMS because of risk of liver toxicity and birth defects. Vanrafia, a selective endothelin A receptor antagonist, was approved on the strength of the ALIGN trial. In that study, it demonstrated a significant 36.1% cut in proteinuria, compared with placebo, after 36 weeks of treatment. Reduction in protein in the urine is a surrogate biomarker for improvement in IgAN, though, and may not translate into actual clinical benefit. And so the ALIGN trial is continuing, with the aim of showing a decline in patients’ estimated glomerular filtration rate (eGFR), a measure of kidney function. Those data could come next year, and the Swiss pharma hopes they will support full FDA approval. But if no benefit on kidney function is seen, the drug could be withdrawn. Two other IgAN drugs — Calliditas Therapeutics’ Tarpeyo and Travere’s Filspari — also gained accelerated approval based on proteinuria reductions. However, when it came to their confirmatory eGFR readouts, Tarpeyo managed a hit and converted to full approval, but Filspari did not — despite posting a stronger effect on proteinuria. As far as Novartis is concerned, that is a problem for the future. Its focus now is on ramping up sales. Novartis obtained Vanrafia via its $3.2 billion acquisition of Chinook Therapeutics in 2023, and the pill will have to do well commercially to help justify that deal. Novartis US President Victor Bultó told Endpoints News ahead of the FDA decision that the company expects atrasentan to reach blockbuster status worldwide. He said that Novartis expects about a population of about 45,000 in the US to be eligible to receive the drug. The company has another Chinook-originated IgAN asset in zigakibart. A subcutaneous anti-APRIL antibody, zigakibart is currently in Phase 3 trials, with results expected in 2026. Novartis has yet another IgAN drug, Fabhalta, which was developed in-house and got US accelerated approval last August . Its pivotal study is continuing, and kidney function data could come late this year. In an interview, Bultó explained that the three treatments tackle the heterogeneous disease in different ways. “For many patients, the damage to the kidney has already happened, so you will need to manage the damage with drugs like atrasentan, drugs like iptacopan [Fabhalta]. What we will do with zigakibart hopefully — the anti-APRILs — is try to work upstream so that damage is minimized and we can treat as soon as possible,” said Bultó. “When we talk with nephrologists, they fully anticipate this to be a combination market, given the heterogeneity of the patients, and today, about 60% of them are already multiple therapies trying to slow down that proteinuria and that progression.” Editor’s note: This article was updated to include further comments from Novartis.

EAST HANOVER, NJ, USA I April 2, 2025 I Novartis today announced the US Food and Drug Administration (FDA) has granted accelerated approval for Vanrafia ® (atrasentan), a potent and selective endothelin A (ETA) receptor antagonist, for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression. This is generally defined as a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g 1 . Vanrafia is a once-daily, non-steroidal, oral treatment that can be added onto supportive care, including a renin-angiotensin system (RAS) inhibitor with or without a sodium-glucose co-transporter-2 (SGLT2) inhibitor 1,2 . Vanrafia was granted accelerated approval based on a prespecified interim analysis of the Phase III ALIGN study measuring the reduction of proteinuria at 36 weeks compared to placebo 1 . It has not been established whether Vanrafia slows kidney function decline in patients with IgAN. The continued approval of Vanrafia may be contingent upon the verification of clinical benefit from the ongoing Phase III ALIGN study evaluating whether Vanrafia slows disease progression as measured by estimated glomerular filtration rate (eGFR) decline at week 136 1 . The eGFR data are expected in 2026 and intended to support traditional FDA approval. “Today’s approval marks an important milestone for people living with IgA nephropathy, offering a new option that can be seamlessly integrated into their existing treatment plan, with no REMS requirement,” said Richard Lafayette, M.D., F.A.C.P., Professor of Medicine, Nephrology and Director of the Glomerular Disease Center at Stanford University Medical Center, and Vanrafia ALIGN Study Investigator and Steering Committee Member. “Vanrafia is a selective ETA receptor antagonist that effectively reduces proteinuria, a major risk factor in IgAN. Taking early, decisive action is critical to help improve outcomes for these patients who too often progress toward kidney failure.” IgAN is a progressive, rare kidney disease in which the immune system attacks the kidneys, often causing glomerular inflammation and proteinuria 10 . With almost 13 out of every million people in the US diagnosed per year, it is one of the most common autoimmune kidney diseases, and each person’s journey is unique 11,12 . Up to 50% of IgAN patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis, often requiring maintenance dialysis and/or kidney transplantation 3-10 , and response to treatment can vary 12,13 . Effective, targeted therapies with different mechanisms of action can help physicians select the most appropriate treatment for patients 12 . “My son was diagnosed with IgA nephropathy long before there were any medicines approved to treat this condition, so the availability of multiple treatment options is incredibly meaningful for this community,” said Bonnie Schneider, Director and Co-Founder, IgA Nephropathy Foundation. “The approval of Vanrafia broadens the treatment landscape and expands the opportunity to tailor care in a disease that can impact each patient so differently.” Data supporting approval In the ongoing Phase III ALIGN study, patients receiving Vanrafia in combination with a RAS inhibitor achieved clinically meaningful and statistically significant proteinuria reduction of 36.1% (P<0.0001) compared to placebo, with results seen as early as week 6 and sustained through week 36 1,2,14 . The effect of Vanrafia on UPCR was consistent across subgroups, including age, sex, race, and baseline disease characteristics, such as eGFR and proteinuria levels, in the main study cohort 1 . A similar treatment effect of Vanrafia was seen in an additional group of patients treated with both a RAS inhibitor and an SGLT2 inhibitor (37.4% reduction in UPCR vs. placebo) 1 . The ALIGN study showed that Vanrafia has a favorable safety profile consistent with previously reported data 1 . Adverse events reported in ≥2% of patients treated with Vanrafia, and more frequently than placebo, include peripheral edema, anemia, and liver transaminase elevation 1 . Because some endothelin receptor antagonists have caused elevations of aminotransferases, hepatotoxicity, and liver failure, clinicians should obtain liver enzyme testing before initiating Vanrafia and during treatment when clinically indicated. Vanrafia may cause serious birth defects 1 . Vanrafia does not require a REMS program. Transforming care in kidney disease “We are proud to expand the treatment landscape in IgA nephropathy with today’s FDA accelerated approval of Vanrafia. IgAN is a heterogenous condition that requires differentiated therapies with unique mechanisms of action, and with our multi-asset kidney disease portfolio, we are well positioned to support a broad patient population and advance care for this disease,” said Victor Bultó, President, US, Novartis. “Building on our longstanding legacy in nephrology, we continue to rapidly grow our capabilities in this space. Each launch enables us to more effectively reach patients with the most suitable treatment option and deliver on our promise to transform kidney disease care.” This is the third US approval received by Novartis for its kidney disease portfolio in the last year, with Fabhalta ® having been granted FDA approval in C3 glomerulopathy (C3G) in March 2025 and accelerated approval in IgAN in August 2024 15 . Fabhalta is also being studied in a broad range of rare kidney diseases, including atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and lupus nephritis (LN). Studies are ongoing to evaluate the safety and efficacy profiles in these investigational indications and support potential regulatory submissions. An investigational subcutaneously administered anti-APRIL monoclonal antibody, zigakibart, is currently in Phase III development in IgAN, with results expected in 2026 16 . About ALIGN The ALIGN study ( NCT04573478 ) is a global, randomized, multicenter, double-blind, placebo-controlled Phase III clinical trial comparing the efficacy and safety of Vanrafia versus placebo in patients with IgAN at risk of progressive loss of kidney function 1,14 . In total, 340 individuals with biopsy-proven IgAN with baseline total proteinuria ≥1 g/day despite optimized RAS inhibitor treatment were randomized to receive once-daily, oral Vanrafia (0.75 mg) or placebo for approximately 132 weeks 1,2 . Patients continue receiving a maximally tolerated and stable dose of a RAS inhibitor as supportive care (unless they are unable to tolerate RAS inhibitor therapy) 1,2 . An additional group of 64 patients receiving an SGLT2 inhibitor for at least 12 weeks was also enrolled 1,2 . The primary efficacy endpoint for the interim analysis is change in proteinuria, a marker of kidney damage, as measured by 24-hour UPCR from baseline to 36 weeks 1,2,14 . Secondary and exploratory objectives include evaluating the change in kidney function from baseline to 136 weeks as measured by eGFR, as well as safety and tolerability 1,14 . Novartis in kidney disease Building on a 40-year legacy that began in transplant, Novartis is on a mission to empower breakthroughs and transform care in kidney health, starting with kidney conditions that have significant unmet need. Historically, these conditions have had considerably less funding and research, leading to a treatment landscape largely focused on reactive or end-stage disease management, often with significant physical, emotional, and financial burdens. Our pipeline targets the underlying causes of disease, with an aim to protect kidney health and delay or prevent dialysis and/or transplantation. Our goal is to help patients get back to living life on their terms—whether at work, in school, or with loved ones, and by partnering with patients, advocates, clinicians and policymakers, we aim to raise awareness, accelerate diagnosis and get patients the right care, sooner. VANRAFIA Indications VANRAFIA is a prescription medicine used to reduce protein in the urine (proteinuria) in adults with a kidney disease called primary immunoglobulin A nephropathy (IgAN) who are at risk of their disease getting worse quickly. It is not known if VANRAFIA is safe and effective in children. VANRAFIA is approved based on a reduction of proteinuria. Continued approval may require results from an ongoing study to determine whether VANRAFIA slows decline in kidney function. Please see full Prescribing Information , including Boxed WARNING and Medication Guide . FABHALTA Indications FABHALTA is a prescription medicine used to: It is not known if FABHALTA is safe and effective in children with PNH, IgAN, or C3G. Please see full Prescribing Information , including Boxed WARNING and Medication Guide . About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach nearly 300 million people worldwide. Reimagine medicine with us: Visit us at https://www.novartis.com and https://www.novartis.us and connect with us on LinkedIn , LinkedIn US , Facebook , X/Twitter , X/Twitter US and Instagram . References SOURCE: Novartis