Novartis AG

BASEL, Switzerland I June 12, 2025 I Novartis announced positive results from APPULSE-PNH, a Phase IIIB study evaluating the efficacy and safety of twice-daily oral monotherapy Fabhalta ® (iptacopan) in adult patients with paroxysmal nocturnal hemoglobinuria (PNH) with Hb levels ≥10g/dL who switched from anti-C5 therapies (eculizumab or ravulizumab) 1 . After 24 weeks of treatment with Fabhalta, the Hb level improved on average by 2.01 g/dL (95% CI, 1.74, 2.29) with most patients achieving normal or near-normal levels 1 . Data will be presented at the European Hematology Association (EHA) Congress 2025. “Today, some patients living with PNH have unmet needs not addressed by eculizumab or ravulizumab,” said Austin Kulasekararaj, Consultant Hematologist, Kings College Hospital and Kings College London. “The positive results from APPULSE-PNH reinforce that Fabhalta can provide clinically meaningful improvements in hemoglobin among patients with higher baseline hemoglobin levels than those enrolled in previous trials, while offering an oral monotherapy for patients.” No patients required transfusion during the study, and the vast majority (92.7%) achieved Hb ≥12g/dL, reaching normal or near-normal levels 1 . Patients treated with Fabhalta also reported clinically meaningful improvements in fatigue (as measured by FACIT-Fatigue score) through Day 168, reaching absolute levels similar to those reported in the general population 1,3,4 . Furthermore, patients treated with Fabhalta maintained intravascular hemolysis control and resolved extravascular hemolysis control, as demonstrated by lactate dehydrogenase levels (<1.5 upper limit of normal) and a reduction in absolute reticulocyte count 1 . “Novartis is dedicated to advancing research and innovation that can transform care and significantly improve the lives of people living with PNH and those who support them,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. “New data from APPULSE-PNH, combined with findings from the Phase III roll-over extension of the APPLY-PNH and APPOINT-PNH studies, reinforce the efficacy and safety profile of Fabhalta in delivering real benefits to patients. Fabhalta is the first and only oral monotherapy currently available for the treatment of adults with PNH, regardless of previous treatment experience.” Alongside APPULSE-PNH, longer-term data from patients initially included in the APPLY-PNH and APPOINT-PNH Phase III studies will be presented at EHA 1 . In APPULSE-PNH and the Phase III roll-over extension study of the APPLY-PNH and APPOINT-PNH studies, Fabhalta was well-tolerated with no new safety signals, consistent with previously reported data 1,5 . About paroxysmal nocturnal hemoglobinuria (PNH) PNH is a rare, chronic and serious complement-mediated blood disorder 6 . People with PNH have an acquired mutation in some of their hematopoietic stem cells (which are located in the bone marrow and can grow and develop into red blood cells [RBCs], white blood cells and platelets) that causes them to produce RBCs that are susceptible to premature destruction by the complement system 6,7 . This leads to intravascular hemolysis (destruction of RBCs within blood vessels) and extravascular hemolysis (destruction of RBCs mostly in the spleen and liver), which cause anemia (low levels of circulating RBCs), thrombosis (formation of blood clots), fatigue and other debilitating symptoms 6,7 . It is estimated that approximately 10-20 people per million worldwide live with PNH 6 . Although PNH can develop at any age, it is often diagnosed in people between 30-40 years old 8,9 . PNH has a significant unmet need not addressed by anti-C5 therapies (eculizumab or ravulizumab). Anti-C5 therapies (eculizumab or ravulizumab) are commonly administered every 2-8 weeks as intravenous infusions, and treatment visits (including journey, waiting, infusion and recovery time) can take approximately 4 to 5 hours 10 . Despite treatment with anti-C5 therapies, a large proportion of people with PNH remain anemic, and some dependent on blood transfusions 7,11-16 . About APPULSE-PNH APPULSE-PNH (NCT05630001) is a Phase IIIB, multinational, multicenter, single-arm, open-label study to evaluate the efficacy and safety of twice-daily oral Fabhalta ® (iptacopan) monotherapy (200mg) in adults with PNH who were switched from anti-C5 therapies (eculizumab or ravulizumab) 2 . The trial enrolled 52 participants who received Fabhalta for 24 weeks 2 . Participants enrolled were required to be on a stable regimen with anti-C5 therapies (eculizumab or ravulizumab) for at least 6 months prior to screening with average hemoglobin (Hb) ≥10g/dL and no red blood cell transfusions in this period 2,17 . The primary endpoint is change from baseline Hb levels after 24 weeks of treatment with Fabhalta 2,17 . About APPLY-PNH APPLY-PNH (NCT04558918) is a Phase III, randomized, multinational, multicenter, active-comparator controlled, open-label trial to evaluate the efficacy and safety of twice-daily, oral Fabhalta ® (iptacopan) monotherapy (200mg) for the treatment of PNH by demonstrating the superiority of Fabhalta compared to anti-C5 therapies (eculizumab or ravulizumab) in adult patients presenting with residual anemia (Hb <10 g/dl) despite a stable regimen of anti-C5 treatment in the last six months prior to randomization 5,18 . About APPOINT-PNH APPOINT-PNH (NCT04820530) is a Phase III, multinational, multicenter, open-label, single-arm study to evaluate the efficacy and safety of twice-daily, oral Fabhalta ® (iptacopan) monotherapy (200mg) in adult PNH patients who are naïve to complement inhibitor therapy, including anti-C5 therapies (eculizumab or ravulizumab) 19,20 . About Fabhalta® (iptacopan) Fabhalta (iptacopan) is an oral, Factor B inhibitor of the alternative complement pathway 21,22 . Discovered at Novartis, Fabhalta received US Food and Drug Administration (FDA) and European Commission (EC) approval in December 2023 and May 2024 respectively for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH) and accelerated approval in the US in August 2024 for the reduction of proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression (generally UPCR ≥1.5 g/g 1.5 g/g) 1,23,24 . In 2025, Fabhalta received FDA and EC approval for the treatment of adults with C3 glomerulopathy (C3G) to reduce proteinuria, making it the first and only treatment approved for this condition 25-31 . Fabhalta is 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 32-35 . 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 connect with us on LinkedIn , Facebook , X/Twitter and Instagram . References SOURCE: Novartis

Novartis unveiled detailed findings from a third late-stage study of its oral complement inhibitor Fabhalta (iptacopan) in paroxysmal nocturnal haemoglobinuria (PNH), demonstrating notable clinical benefits when switching from anti-C5 therapies to twice-daily Fabhalta monotherapy. Results from the 52-participant Phase IIIB APPULSE-PNH study top-lined in December last year, showed that average haemoglobin (Hb) levels increased from baseline after 24 weeks of Fabhalta monotherapy in patients on a stable regimen of anti-C5 therapies — AstraZeneca’s Soliris (eculizumab) or Ultomiris (ravulizumab) — for ≥6 months before screening, with baseline Hb ≥10 g/dL and no transfusions during that period.New data released on Thursday ahead of the European Haematology Association (EHA) Congress, showed that switching from anti-C5 therapies to Fabhalta led to an average Hb increase of 2.01 g/dL, with 92.7% of patients reaching normal or near-normal levels at 24 weeks. Notably, no patients required transfusion during the study period.Fabhalta recipients also reported significant improvements in fatigue on the FACIT-Fatigue scores by day 168, reaching absolute levels seen in the general population. Moreover, the treatment maintained intravascular haemolysis control whilst resolving extravascular haemolysis, demonstrated through sustained lactate dehydrogenase levels below 1.5 times the upper limit of normal and reduced absolute reticulocyte counts.Safety-wise, the drug was well-tolerated, with no new signals identified, consistent with previous studies.The results build on the earlier Phase III trials — APPLY-PNH and APPOINT-PNH in previously treated patients and the complement inhibitor-naïve patients, respectively, which supported Fabhalta’s approval for indication in the US and EU. “New data from APPULSE-PNH, combined with findings from…APPLY-PNH and APPOINT-PNH studies, reinforce the efficacy and safety profile of Fabhalta in delivering real benefits to patients," said Shreeram Aradhye, chief medical officer at Novartis.Besides PNH, Fabhalta also holds FDA approvals for IgA nephropathy and complement 3 glomerulopathy.

As well as the $350 million upfront fee, the deal will mean Philochem is eligible for up to $1 billion in in development, regulatory and commercial milestones.\n Bristol Myers Squibb, via its RayzeBio unit, is handing $350 million in upfront cash for a phase 1-stage radiopharmaceutical therapy and diagnostic for prostate cancer.The deal centers around OncoACP3, a small-molecule ligand with high affinity for acid phosphatase 3 (ACP3), a phosphatase that is expressed in prostate cancer. The drug has been developed by Swiss biotech Philochem, which is assessing the asset in a phase 1 trial as a PET radiotracer for the diagnostic imaging of prostate cancer.Initial data from the first cohort of patients in this trial have been promising, “displaying selective tumour uptake and long residence time with minimal healthy tissue uptake,” Philochem explained in a June 10 post-market release. The Otelfingen, Switzerland-based company is currently gearing up to request FDA permission to launch a phase 1 study of OncoACP3 as a therapeutic drug.As well as the $350 million upfront fee, the deal will mean Philochem is eligible for up to $1 billion in development, regulatory and commercial milestones on top of mid single- to low double-digit royalties on sales of the drug should it make it to market as either a cancer therapy or diagnostic agent.BMS entered the radiopharma space via its $4.1 billion buyout of RayzeBio at the end of 2023. Unlike Novartis’ approved radiopharma therapies Lutathera and Pluvicto, which use a beta-emitting isotope called lutetium, RayzeBio’s platform is based on an alpha-emitting isotope called actinium-225.“OncoACP3, with its initial encouraging safety profile, provides a differentiated entry for Bristol Myers Squibb and RayzeBio into the prostate cancer arena, building on our leadership in actinium-based RPT development,” RayzeBio President Ben Hickey said in yesterday’s release. “This collaboration with Philochem enhances our leadership in the rapidly advancing radiopharmaceuticals space, consistent with our strategy to bring forward best-in-class RPT candidates,” Hickey added.Philochem—which is a subsidiary of Italy’s Philogen Group—also has a couple of clinical-stage therapeutic and diagnostic candidates that are focused on fibroblast activation protein, which is overexpressed in more than 90% of epithelial cancers.The radiopharma field is expected to grow from $9.1 billion in 2023 to $26.5 billion in 2031, according to a January report by Insight Partners. This year has already seen some intriguing radiopharma readouts, including “promising efficacy” for Telix Pharmaceuticals’ radiation therapy for brain cancer and ITM Isotope Technologies’ stomach and pancreatic cancer tumor candidate besting the standard of care while unable to prove a statistically significant benefit in median overall survival.