STAMP

Scemblix demonstrated sustained superior major molecular response (MMR) vs. all investigator-selected TKIs (74.1% vs. 52%) and vs. imatinib alone (76.2% vs. 47.1%), meeting both ASC4FIRST 96-week key secondary endpoints1 Scemblix showed a clinically relevant 15.1% higher MMR rate vs. second generation (2G) TKIs (72.0% vs. 56.9%)1 96-week data extend favorable safety and tolerability profile for Scemblix vs. imatinib and 2G TKIs, with fewer grade ≥3 AEs and less than half the discontinuation rate due to AEs1 Latest results strengthen Scemblix as a standard of care following expanded indication in newly diagnosed and previously treated adult patents with Ph+ CML-CP and NCCN category 1 recommendation1-3 Basel, December 8, 2024 – Novartis today announced positive, longer-term results from the pivotal Phase III ASC4FIRST trial with Scemblix® (asciminib) showing superior major molecular response (MMR) rates at week 961. The study compared the MMR rate of Scemblix to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) (imatinib, nilotinib, dasatinib and bosutinib) and to imatinib alone in adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) at the week 96 evaluation, the study’s key secondary endpoints1. The longer-term results showed an increasing difference in Scemblix MMR rate vs. SoC, vs. imatinib and vs. 2G TKIs (nilotinib, dasatinib and bosutinib)1. Results were presented at the 66th American Society of Hematology Annual Meeting & Exposition (ASH)1. “These 96-week results are very encouraging for clinicians who aspire to obtain a balance of efficacy and tolerability profiles to help newly diagnosed adult CML patients achieve and maintain treatment goals,” said Jorge Cortes, M.D., Director, Georgia Cancer Center. “The sustained superior efficacy, deeper and more durable responses, and favorable safety and tolerability profile compared to standard of care TKIs continue to support the promise of Scemblix as a potentially practice-changing treatment option.” The median follow-up was 2.2 years for Scemblix and investigator-selected SoC TKIs1. Over 22% more patients treated with once-daily Scemblix achieved MMR at week 96 vs. all investigator-selected SoC TKIs, and nearly 30% more patients achieved MMR at week 96 vs. imatinib alone1. The Scemblix MMR rate was 15.1% (95% CI: 2.3, 28.0; not crossing zero) higher vs. 2G TKIs (72% vs. 56.9%)1. Patients treated with Scemblix also achieved deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs1. OverallaScemblix (n=201)vs. IS SoC TKIs (n=204) Imatinib stratumbScemblix (n=101)vs. imatinib (n=102) 2G TKI stratumcScemblix (n=100) vs. 2G TKIs (n=102) Key secondary endpoints MMR rates at week 96 74.1% vs. 52% 76.2% vs. 47.1% Secondary endpointsd MMR ratesat week 96 72% vs. 56.9% MR4at week 96 48.8% vs. 27.5% 52.5% vs. 23.5% 45% vs. 31.4% MR4.5at week 96 30.9% vs. 17.7% 35.6% vs. 11.8% 26% vs. 23.5% a All patients receiving Scemblix (n=201) or investigator-selected SoC TKIs (n=204). Treatment difference after adjusting for pre-randomization selected TKI and EUTOS long-term survival (ELTS) risk groups at baseline.b The 203 patients within the pre-randomization-selected imatinib stratum were randomized to receive either Scemblix (n=101) or imatinib (n=102). Treatment difference after adjusting for ELTS risk groups at baseline. c The 202 patients within the pre-randomization selected 2G TKIs stratum were randomized to receive either Scemblix (n=100) or 2G TKIs (n=102: nilotinib, 48%; dasatinib, 41%; bosutinib, 11%). d Secondary endpoints were not powered for statistical significance. The safety profile of Scemblix at 96-weeks was consistent with the 4-year follow-up of the Phase III ASCEMBL trial, with no new safety concerns observed to date1,2,4. Fewer grade ≥3 AEs and dose adjustments to manage AEs were reported for Scemblix, and discontinuation due to AEs was more than 50% lower for Scemblix vs. both imatinib and 2G TKIs1. The most frequent AEs (≥15%) were diarrhea, headache, fatigue, musculoskeletal pain, and rash1. Week 96 Scemblixn=200 Imatinibn=99 2G TKIsn=102 Grade ≥ AEsa 44.5% 49.5% 59.8% Discontinuation due to AEsa 5.5% 13.1% 12.7% AEs leading to dose adjustments/interruptionsa 33% 41.4% 57.8% aIn patients who experienced ≥1 adverse event. Novartis also presented today at ASH interim data from the Phase II ASC2ESCALATE dose-escalation study in both the second line (2L) and newly diagnosed Ph+ CML-CP settings5. In the analysis of 2L patients at week 24 (n=28) Scemblix demonstrated MMR rates of 42.9% and deep molecular responses (MR4 25% and MR4.5 10.7%), with a consistent safety and tolerability profile5. The most common AEs (>15%) were nausea, hypertension, and vomiting5. “Novartis’ decades-long work in CML and deep relationships within the community have informed our Scemblix clinical trial program of over 10 years, the centerpiece of our continuing drive to address ongoing unmet medical needs for people with CML,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. “These latest findings reinforce the differentiated efficacy, safety and tolerability profile of Scemblix in newly diagnosed and previously treated adult CML patients.” Scemblix was recently granted accelerated approval in the US to treat newly diagnosed adults with Ph+ CML-CP, which together with its approval in previously treated adult patients with Ph+ CML-CP expands the population of Scemblix-eligible patients by four-fold 2. In addition, the National Comprehensive Cancer Network (NCCN) updated its Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for the treatment of CML, recommending asciminib as a category 1 – preferred treatment for newly diagnosed Ph+ CML-CP and across all risk categories3. About the ASC4FIRST Phase III Clinical Trial ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix® 80 mg QD vs. IS first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP2,6. The trial met both primary endpoints with Scemblix demonstrating superior MMR rates at week 48 vs. investigator-selected SoC TKIs (imatinib, nilotinib, dasatinib and bosutinib) (67.7% vs. 49.0%) and imatinib alone (69.3% vs. 40.2%) as well as the secondary, non-powered endpoint for the 2G TKI stratum of (66% vs 57.8%)1,6. The study remains ongoing with further efficacy and safety readouts planned. About the ASC2ESCALATE Phase II StudyASC2ESCALATE (NCT05384587) is a Phase II, multicenter, single-arm, dose-escalation study of oral Scemblix® 80 mg QD in both the second line (2L) and newly diagnosed (1L) Ph+ CML-CP settings in the US 5,7. While Scemblix is already approved across lines of therapy, this is the first prospective trial to assess asciminib in the 2L setting and a dose-escalation strategy of asciminib as 2L and 1L treatment for patients with CML-CP not meeting molecular milestones 5. The proportion of patients achieving MMR at 12 months in the 2L setting will be measured as the primary endpoint 5. The study remains ongoing and has completed enrollment with 196 patients (100 patients in 2L, 96 patients in 1L)5. About Scemblix® (asciminib) Scemblix® is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature)4,8,9. Other currently approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive)9. In the US, Scemblix was granted accelerated approval to treat newly diagnosed adults with Ph+ CML-CP and is also approved for previously treated adult patients with Ph+ CML-CP. Outside the US, it is approved in more than 75 countries, including the EU, to treat those who have previously been treated with two or more TKIs with Ph+ CML-CP2,10,11. In some countries, including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation2,3,10. Scemblix is being studied across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination2,4,6,8,10,12-24. Patient Access and Support Novartis, with its 20+ year history in CML, is committed to continuing to address areas of unmet patient need and reducing barriers to patient access and affordability that prevent patients from benefiting from innovation. Novartis Patient Support is available to help guide eligible patients through the various aspects of getting started on treatment including help understanding insurance coverage and identifying potential financial assistance options. Patients or providers can call 866-433-8000 or visit support.scemblix.com to learn more. About Novartis Commitment to CML Novartis has a long-standing scientific commitment to patients living with CML. For more than two decades, our bold science has helped transform CML from a life-limiting condition for many patients. Despite these advancements, there’s still work to be done. We continue to research ways to target the disease more selectively and to address the challenges of not reaching treatment efficacy goals, experiencing treatment resistance and/or intolerance that many patients face. Our legacy inspires our future innovation – we continue to lead the way in developing novel medicines to address serious unmet needs in CML. Our commitment also goes beyond science. Our 20+ year collaboration with the Max Foundation has provided access to Gleevec (imatinib), Tasigna (nilotinib) and now Scemblix and is delivering tremendous patient impact in low- and middle-income countries, with over 100,000 patients supported to date. Disclaimer This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “may,” “committed,” “contingent,” “lead,” “continue,” “ongoing,” “to deliver,” “allowing,” “continuing,” “commitment,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for Scemblix, or regarding potential future revenues from Scemblix. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Scemblix will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Scemblix will be commercially successful in the future. In particular, our expectations regarding Scemblix could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. 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 more than 250 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 Cortes JE, Hochhaus A, Hughes TP, et al. Asciminib Continues to Provide Superior Efficacy and Favorable Safety and Tolerability vs Tyrosine Kinase Inhibitors In Newly Diagnosed Chronic Myeloid Leukemia in ASC4FIRST: Week 96 Update. Presented at: 66th ASH Annual Meeting & Exposition; December 7 – 10, 2024; San Diego, CA. Scemblix (asciminib) Prescribing information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; October 2024. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Chronic Myeloid Leukemia Version 2.2025. November 13, 2024. Accessed November 22, 2024. https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf Rea D, Mauro MJ, Boquimpani C, et al. A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After 2 or more prior TKIs. Blood. 2021;138(21):2031-2041. doi:10.1182/blood.2020009984 Atallah EL, Levy MY, Koller P, et al. Efficacy and Safety of Asciminib in Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Interim Results from the Phase 2 ASC2ESCALATE Trial in the Cohort of Patients (Pts) after 1 Prior Tyrosine Kinase Inhibitor (TKI). Presented at: 66th ASH Annual Meeting & Exposition; December 7 – 10, 2024; San Diego, CA. A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP (ASC4FIRST). ClinicalTrials.gov identifier: NCT04971226. Updated March 25, 2024. Accessed March 26, 2024. https://clinicaltrials.gov/study/NCT04971226 Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia (ASC2ESCALATE) ClinicalTrials.gov identifier: NCT05384587. Updated October 30, 2024. Accessed November 21, 2024. https://clinicaltrials.gov/study/NCT05384587 Cortes JE, Hughes TP, Mauro MJ, et al. Asciminib, a First-in-Class STAMP Inhibitor, Provides Durable Molecular Response in Patients (pts) with Chronic Myeloid Leukemia (CML) Harboring the T315I Mutation: Primary Efficacy and Safety Results from a Phase 1 Trial. Oral presentation at: ASH Annual Meeting; Dec. 7, 2020. Schoepfer J, Jahnke W, Berellini G, et al. Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1. J Med Chem. 2018;61(18):8120-8135. doi:10.1021/acs.jmedchem.8b01040 Novartis data on file. Scemblix. EMA Summary of Product Characteristics. Novartis Europharm Limited; 2022. Wylie AA, Schoepfer J, Jahnke W, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1. Nature. 2017;543(7647):733-737. doi:10.1038/nature21702   Hughes TP, Mauro MJ, Cortes JE, et al. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019; 381(24):2315-2326. doi:10.1056/NEJMoa1902328     Hughes TP, et al. Expanded Phase 1 Study of ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Reveals Significant and Durable Responses in Patients with CML-Chronic Phase with Failure of Prior TKI Therapy. Presented at: ASH Annual Meeting & Exposition; Dec. 5, 2016.   Ottmann OG, Alimena G, DeAngelo DJ, et al. ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Exhibits Safety and Promising Single- Agent Activity in a Phase I Study of Patients with CML with Failure of Prior TKI Therapy. Blood. 2015;126(23):138. doi:10.1182/blood.V126.23.138.138   Mauro MJ, Kim DW, Cortes J, et al. Combination of Asciminib Plus Nilotinib (NIL) or Dasatinib (DAS) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Presented at: EHA Annual Meeting; June 15, 2019.   Cortes JE, Lang F, Kim DW, et al. Combination Therapy Using Asciminib Plus Imatinib (IMA) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study. Presented at: EHA Annual Meeting; June 15, 2019.   Manley PW, Barys L, Cowan-Jacob SW. The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase. Leuk Res. 2020;98:106458. doi:10.1016/j.leukres.2020.106458   Study of Efficacy of CML-CP Patients Treated with ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs. ClinicalTrials.gov identifier: NCT03106779. Updated February 7, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT03106779   Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and WithoutT315I Mutation (AIM4CML). ClinicalTrials.gov identifier: NCT04666259. Updated September 7, 2023. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT04666259   Study of Efficacy And Safety Of Asciminib In Combination With Imatinib In Patients With Chronic Myeloid Leukemia In Chronic Phase (CML-CP). ClinicalTrials.gov identifier: NCT03578367. Updated March 22, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT03578367   Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors. ClinicalTrials.gov identifier: NCT04795427. Updated October 19, 2023. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT04795427   A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL. ClinicalTrials.gov identifier: NCT02081378. Updated March 18, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT02081378   Asciminib Treatment Optimization in ≥ 3rd Line CML-CP. ClinicalTrials.gov identifier: NCT04948333. Updated February 28, 2024. Accessed April 3, 2024. https://clinicaltrials.gov/ct2/show/NCT04948333  # # # Novartis Media RelationsE-mail: media.relations@novartis.com Central North America Anja von Treskow +41 79 392 9697 Michael Meo +1 862 274 5414 Anna Schäfers +41 79 801 7267 Switzerland Satoshi Sugimoto +41 79 619 2035 Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: investor.relations@novartis.com Central North America Isabella Zinck +41 61 324 7188 Sloan Simpson +1 862 345 4440 Nicole Zinsli-Somm +41 61 324 3809 Jonathan Graham +1 201 602 9921 Imke Kappes +41 61 324 8269 Parag Mahanti +1973 876 4912

ROCKVILLE, Md. and SUZHOU, China, Nov. 21, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily for malignancies, announced today that findings from a phase Ib multicenter clinical trial (NCT04260022) of its third-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) have been published in the November 2024 issue of JAMA Oncology, marking a milestone in global awareness concerning the agent. JAMA Oncology is among the most influential and high-ranking oncology publications, with a 2023 impact factor of 28.4. It is read widely by the clinical-oncology community, with 6.4 million original downloads or views per annum. In 2023, the journal accepted only about 155 (7%) of 2,223 research-article submissions. Olverembatinib may help to address critical unmet clinical needs related to TKI treatment resistance and intolerance, which can impose formidable humanistic and economic burdens especially in heavily pretreated patients with suboptimal outcomes. For instance, arterial occlusive events (AOEs) constitute one salient and potentially dose-limiting treatment challenge with certain second- and third-generation TKIs. This study (NCT04260022) randomly allocated 80 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) to receive oral olverembatinib 30, 40, or 50 mg on alternate days. The study population was heavily pretreated: approximately 18% of patients had received two prior TKIs, 28% three, and 54% at least four. Forty-six patients (57.5%) had received ponatinib; 25 (31.3%), asciminib; and 11 (13.8%), both medications.1 Among all evaluable patients with chronic-phase CML (CP-CML), the complete cytogenetic response (CCyR) rate was approximately 61% and the major molecular response (MMR) rate, approximately 42%. Cytogenetic and molecular responses were similar irrespective of the presence of the T315I mutation, which confers resistance against imatinib and all second-generation TKIs.1 Importantly, approximately 58% of patients with prior ponatinib treatment failure achieved CCyR and about 37%, MMR. Corresponding values in patients with asciminib treatment resistance were 50% and 33%.1 Olverembatinib was also well tolerated, with leading (typically mild or moderate) treatment-emergent adverse events including elevated blood creatine phosphokinase and thrombocytopenia. There were no fatal treatment-related adverse events. Treatment-related AOEs were infrequent (3%) and mild or moderate (grade 1 or 2); no such olverembatinib-related event was considered serious. "I am delighted to showcase the strength and progress of the 'lead' asset of Ascentage Pharma, which exemplifies the richness and diversity of our product pipeline of innovative, patient-centric therapies for a range of hematologic malignancies," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "In the future, we will continue to advance these development programs in efforts to bring more treatment options to patients with unmet clinical needs around the world." "One potential explanation for the response of olverembatinib in patients with ponatinib and asciminib resistance is its broad (pan-BCR::ABL1-kinase domain) mutational coverage," said principal investigator Elias Jabbour, MD, Professor of Leukemia at The University of Texas MD Anderson Cancer Center. "In studies to date, olverembatinib has shown greater sensitivity and clinical benefit against compound mutations – two or more mutations within the same allele of BCR::ABL1 – compared with other approved TKIs and the STAMP inhibitor asciminib." Findings from this trial have also been presented at leading hematologic-oncology congresses around the world, including the 29th European Hematology Association Congress, which convened June 13-16, 2024, in Madrid; the 12th annual meeting of the Society of Hematologic Oncology, on September 4-7, 2024, in Houston, Texas; and the ESH-iCMLf 26th Annual John Goldman Conference on Chronic Myeloid Leukemia (Biology and Therapy), on September 27-29, 2024, in Prague. Updated results will be presented at the 66th American Society of Hematology Annual Meeting and Exposition, December 8, 2024 (6:00-8:00 PM), in San Diego, CA (poster/publication #3151). "Publication of our trial results in JAMA Oncology represents a major milestone for olverembatinib, and the study established the recommended dose for our ongoing phase III registrational trial: POLARIS-2 [NCT06423911]," said Dr. Dajun Yang, Chairman & CEO of Ascentage. "We look forward to that trial and, in the future through our option agreement with Takeda, to potentially bring this medication to underserved populations around the world, including patients with CML or Ph⁺ ALL that is resistant to or intolerant of other medications." On June 14, 2024, Ascentage signed an exclusive option agreement to enter into an exclusive license agreement with Takeda () for olverembatinib. In the event that Takeda exercises the option, Takeda would license the global rights to develop and commercialize olverembatinib in all territories outside of, among others, mainland China, Hong Kong, Macau, and Taiwan, China. Olverembatinib is currently approved in China for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic phase CP-CML or accelerated-phase CML harboring the T315I mutation as confirmed by a validated diagnostic test. It is also approved for adult patients with CP-CML resistant to and/or intolerant of first- and second-generation TKIs. It remains investigational in other parts of the world. Reference 1. Jabbour E, Oehler VG, Koller PB, et al. Olverembatinib after failure of tyrosine kinase inhibitors, including ponatinib or asciminib: a phase 1b randomized clinical trial. JAMA Oncol 2024. doi:10.1001/jamaoncol.2024.5157 About Ascentage Pharma Ascentage Pharma (6855.HK) is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily in malignancies. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. The company has built a rich pipeline of innovative drug candidates that includes novel, highly potent Bcl-2 and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation TKIs. Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 13 registrational studies (completed/ ongoing/planned). Olverembatinib, the company's first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted Orphan Drug Designations (ODDs) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, National Cancer Institute and the University of Michigan. The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions and expectations or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions and expectations may alter in light of future development. 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A pharmaceutical ingredient that’s been a key component in nasal decongestants for decades is having its efficacy called into question, and the FDA is now weighing whether to change the compound’s regulatory status — potentially leading to many widely used over-the-counter cold and allergy products being pulled from pharmacy shelves. But before the FDA takes any action, it wants to hear what the public thinks. The ingredient, oral phenylephrine, by itself and in combination with other active ingredients, is in decongestants sold under numerous brand names, such as Sudafed and Mucinex. All products containing oral phenylephrine continue to be available to consumers for now. But on Thursday, the FDA proposed an order that would remove oral phenylephrine from its non-prescription drugs guidelines, called the OTC Monograph. The regulator emphasized that this proposed order is due to lack of efficacy, not because of safety. At one time, phenylephrine was rare in decongestants because pseudoephedrine was the preferred active ingredient. But that compound can be made into the methamphetamine. Efforts to curb meth production led to the Combat Methamphetamine Act of 2005, which moved pseudoephedrine-containing drugs behind pharmacy counters. Drugmakers responded by making more products with oral phenylephrine, which is not covered by this law. presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB Last year, an FDA advisory committee discussed phenylephrine and unanimously voted that current scientific data do not support the ingredient’s efficacy as a nasal decongestant. The committee raised no concerns about the safety of oral phenylephrine when used at the recommended dose. The FDA now says it has conducted a comprehensive review of all available safety and efficacy data for oral phenylephrine as a nasal decongestant, including historical data used to support the compound 30 years ago. Speaking during a conference call with journalists Thursday, Theresa Michele, director of the FDA’s office of nonprescription drugs, said new data had become available since the advisory committee meeting, which the agency also reviewed. “At this point, based on the available data, and taking into account the advice of the advisory committee, we are proposing that oral phenylephrine is not effective to relieve nasal congestion at the recommended dose set forth in the monograph,” Michele said. Phenylephrine is also an ingredient in some nasal spray decongestants. The FDA’s proposal does not extend to such products. The proposed FDA order can be found here. Public comments may be submitted here (use docket number FDA-2024-N-4734 ) through May 7, 2025. After considering the comments, the agency may issue a final order removing oral phenylephrine from its guidelines, which would mean nasal decongestants could no longer contain the compound. Michele said the FDA would then provide manufacturers with time to either reformulate their medicines or remove oral phenylephrine-containing products from the market. Don’t let the autumn sniffles get you down. Here’s a look back at other recent regulatory news, including U.S. and European actions on several novel medications (alas, no new decongestants): Exclusive Heard at HLTH 2024: Insights from Innovative Healthcare Executives Executives from Imagine360, Verily, BrightInsight, Lantern, and Rhapsody shared their approaches to reducing healthcare costs and facilitating digital transformation. By MedCity News Decisions for Drugs and Devices —The FDA needs more time to review Organon drug Vtama as a treatment for atopic dermatitis. The company said the regulator has pushed out the December target date for a decision by three months to March 12, 2025. Vtama is from Roivant Sciences subsidiary Dermavant, which Organon recently acquired for $175 million up front. Under Dermavant, the topical drug won FDA approval in 2022 as a treatment for plaque psoriasis. —Novartis cancer drug Scemblix expanded its FDA-approved uses to include the treatment of newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ PML). The tablet, part of a class of drugs called STAMP inhibitors, initially landed accelerated FDA approval in 2021 as a treatment for advanced cases of Ph+ PML. —The FDA approved Iterum Therapeutics antibiotic Orlynvah. The regulatory decision covers the treatment of uncomplicated urinary tract infections in women who have limited or no oral antibacterial treatment options. The drug, whose main ingredient is sulopenem, is taken as a tablet twice daily for five days. —Astellas Pharma landed FDA approval for zolbetuximab, brand name Vyloy, as a treatment for gastric or gastroesophageal junction adenocarcinoma. It’s the first FDA approval for a drug targeting the cancer protein claudin 18.2 (CLDN18.2). The regulatory decision specifically covers patients whose cancer is negative for a different cancer protein called HER2. Drugs are already available for HER2-positive cancers. —In other Astellas news, the Japanese pharma company withdrew its European Medicines Agency application for geographic atrophy drug avacincaptad pegol. The company said it made the decision after discussions with the agency’s Committee for Medicinal Products for Human Use. The drug, administered as a once-monthly eye injection, won FDA approval in geographic atrophy last year and is marketed in the U.S. under the brand name Izervay. Failure to secure approval in Europe will make it harder for Astellas to recoup the $5.9 billion it spent to acquire Iveric Bio, the company that developed the drug. —Pfizer respiratory syncytial virus vaccine Abrysvo expanded its FDA approval to include adults age 18 through 59, broadening the market for the product. The initial FDA approval of Abrysvo last year covered patients age 60 and older. It’s also approved for use by pregnant individuals as a maternal vaccine; antibodies produced by the mother confer protection against RSV intended to last from the baby’s birth up to six months of age. —Gilead Sciences’ Trodelvy will no longer be available in the U.S. for treating urothelial carcinoma, an aggressive bladder cancer. After discussions with the FDA, the company decided to voluntarily withdraw the product, which had won accelerated approval in this indication in 2021. In May, the company reported Trodelvy failed its confirmatory Phase 3 test in advanced urothelial carcinoma. The withdrawal in urothelial carcinoma does not affect drug’s approved uses in breast cancer. —After previous regulatory setbacks, AbbVie finally landed FDA approval for Vyalev, a Parkinson’s disease drug/device combination product that provides 24 hour subcutaneous infusion of the medications foscarbidopa and foslevodopa. Last year, the regulator turned down the product’s application, asking for more information about the pump in the device. The FDA did not raise any questions about safety or efficacy, nor did it ask for another clinical trial. This past June, the agency again turned down AbbVie’s application for issues at the product’s third-party manufacturer. —There’s a new Pfizer drug for both hemophilia A and B. The FDA approved the antibody drug marstacimab for preventing or reducing frequency of bleeding episodes in patients 12 and older. Pfizer will market the drug under the brand name Hympavzi. As a once-weekly injectable medication, Hympavzi will provide an alternative to IV-infused hemophilia therapies. —The FDA needs more time to review Intercept Pharmaceuticals’ application seeking full regulatory approval of Ocaliva, which had received accelerated approval in 2016 for the rare liver disease primary biliary cholangitis. Intercept, now a subsidiary of Alfasigma, said the agency did not provide a new date for a regulatory decision. —Alzheimer’s disease drug Leqembi hit a regulatory obstacle in Australia, where the Therapeutic Goods Administration decided against registering the medication. Eisai said it will request a reconsideration as permitted under Australian law. It’s the second setback for the drug in recent months. Over the summer, the drug received a negative opinion from a European Medicines Agency committee concerned about the risk of severe side effects and limited benefit. Leqembi has approvals in the U.S., Japan, China, and several other markets. —The FDA approved a Thermo Fisher Scientific companion diagnostic to Voranigo, a Servier Pharmaceuticals’ drug approved over the summer for treating patients whose glioma is driven by mutations to IDH1 or IDH2 enzymes. The diagnostic, called Ion Torrent Oncomine Dx Target Test, identifies patients whose cancer carries the genetic signature making them eligible for treatment with the Servier drug. —Advanced cases of non-small cell lung cancer can now be treated with a wearable device. The FDA approved Novocure’s Optune Lua, a wearable technology that kills cancer cells with electrical signals administered via electrodes placed on the skin. Novocure’s “tumor-treating field” technology was first approved in 2011 as a treatment for a recurrent type of brain cancer. —The FDA rejected Zealand Pharma’s dasiglucagon, a drug developed to prevent and treat hypoglycemia in children who have the rare disease congenital hyperinsulinism. According to the Copenhagen-based biotech, the regulator cited issues at a third-party manufacturer. The FDA did not raise any concerns about the drug’s clinical data or safety. Advisory Committee Outcomes —An FDA advisory committee voted 11 to 3 that the benefits of Lexicon Pharmaceuticals’ sotagliflozin do not outweigh its risks when used as an adjunct to insulin to treat adults with type 1 diabetes and chronic kidney disease. But some committee members expressed support for use of the drug in subpopulations of patients. Sotagliflozin, given the brand name Zynquista, is expected to receive an FDA decision by Dec. 20. Sotagliflozin was approved last year for the treatment of heart failure and is marketed as Inpefa in this indication. —The European Medicine Agency’s Committee for Medicinal Products for Human Use yet again recommended against renewing the marketing authorization for Translarna, a PTC Therapeutics drug for Duchenne muscular dystrophy. Translarna received conditional marketing authorization in 2014. After the drug failed its Phase 3 study, the committee twice recommended against renewing the authorization. The latest opinion comes after the EMA directed the committee to reconsider, taking into account “the totality of evidence.” The committee said its reassessment “concluded that the effectiveness of Translarna has not been confirmed.” —Stealth BioTherapeutics moved a step closer to potential approval of the first drug for Barth syndrome. An FDA advisory committee voted 10 to 6 that Stealth’s drug, elamipretide, was effective at treating the ultra-rare mitochondrial disorder. The committee vote follows several regulatory setbacks, including a 2021 refuse-to-file letter in which the FDA pointed out that elamipretide failed its clinical trial. Stealth maintains there was improvement in a subgroup of patients and the short duration of treatment is the reason for the trial failure. An FDA decision is expected by Jan. 29. What’s New in Covid-19 —The European Commission granted marketing authorization to Novavax’s updated Covid-19 vaccine, Nuvaxovid. Authorization for the protein-based vaccine covers its use in those age 12 and older. The FDA authorized the updated version of Novavax’s Covid-19 vaccine in September. —In other Novavax Covid-19 news, the FDA pressed pause on the company’s plans for late-stage testing of a combination flu/Covid-19 vaccine as well as a standalone influenza vaccine. According to Novavax, the clinical hold stems from a report of motor neuropathy in a single patient outside the U.S. who received the combination vaccine in a Phase 2 study. The trial was completed in July 2023 and the serious adverse event was reported in September. Novavax said previous Covid-19 and influenza trials showed no signs of motor neuropathy. The company’s standalone Covid-19 vaccine is unaffected by the clinical hold. —In Covid-19 and flu testing news, the FDA granted marketing authorization to a Healgen Scientific over-the-counter, at-home test for both pathogens. The OTC Healgen Rapid Check Covid-19/Flu A&B Antigen Test uses a sample from a nasal swab. The authorization covers use of the product by people age 14 and older within five days of the start of symptoms. For children as young as 2, the sample must be collected by an adult.