Portola Pharmaceuticals LLC

In 2024, China approved several new drugs, and more blockbuster drugs are expected to be launched in 2025, covering oncology, autoimmune diseases, rare diseases, and other therapeutic areas.   Drug Name Mechanism of Action Indications Development Institutions Evantuzumab c-Met/EGFR bispecific antibody Non-small cell lung cancer Johnson & Johnson; Genmab Taqetuzumab CD3/GPRC5D bispecific antibody Multiple myeloma Johnson & Johnson; Genmab Zenidatuzumab Anti-HER2 bispecific antibody Biliary tract cancer Zymeworks; Jazz Pharmaceuticals; BeiGene Inalises PI3Kα inhibitor HR-positive breast cancer Roche; Chugai Pharmaceutical Asunitinib STAMP allosteric inhibitor Speculated use for chronic myeloid leukemia treatment Novartis Tazemetostat EZH2 inhibitor Follicular lymphoma Epizyme; Huadong Medicine; Eisai Relatuzumab-alpha PDL1/TGF-β bispecific antibody Stomach cancer; gastroesophageal junction cancer Hengrui Medicine; Dong-A Pharma Vabysmo EGFR antibody-drug conjugate Nasopharyngeal cancer Lepu Biopharma Tenapanor NHE3 inhibitor Chronic kidney disease hyperphosphatemia Ardelyx; Kyowa Kirin; Fosun Pharma; AstraZeneca Mersutide OXM analog; GLP-1R/GCGR agonist Obesity Eli Lilly; Innovent Biologics Vusirumab IL-1β monoclonal antibody Gouty arthritis Junshi Biosciences Romosozumab SOST monoclonal antibody Osteoporosis Astellas; Amgen; UCB Teplizumab CD3 monoclonal antibody Type 1 diabetes Ligand Pharmaceuticals; Johnson & Johnson; Sanofi Solrepinib Syk inhibitor Immune thrombocytopenic purpura Huadong Medicine BBM-H901 Factor IX gene therapy Hemophilia B Gene Therapy Fitusiran RNAi therapy Hemophilia A; Hemophilia B Sanofi; Alnylam Andexanet alfa Recombinant factor Xa Factor Xa inhibitor antidote Portola Pharmaceuticals Lisocabtagene maraleucel IL-23p19 monoclonal antibody Crohn's disease Boehringer Ingelheim; AbbVie Lemborexant & Daridorexant OX1R antagonist; OX2R antagonist Insomnia Eisai & Idorsia; Sihuan Pharmaceutical; Nxera Pharma Highlights of new drug approvals in 2024 include: 1. Oncology: The world’s first antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα) for ovarian cancer: Mirvetuximab soravtansine. PD-1/VEGF bispecific antibody envafolimab and Nectin-4 ADC enfortumab vedotin. 2. Autoimmune diseases: IL-17A/F monoclonal antibody bimekizumab for ankylosing spondylitis. 3. Rare diseases: Novartis’ complement factor B inhibitor for paroxysmal nocturnal hemoglobinuria (PNH).   Blockbuster drugs expected to be approved in 2025 include: Oncology: Amivantamab (Q1) The world’s first c-Met/EGFR bispecific antibody. Highlight: Phase III study showed significant extension of median progression-free survival (mPFS). Talquetamab (Q2) A CD3/GPRC5D bispecific antibody and the world’s first drug targeting GPRC5D. Clinical results: Objective response rate (ORR) in Chinese patients was 69.0%-73.6%. Zanidatamab (Q2) A HER2-targeting bispecific antibody based on Azymetric™ technology. Indication: HER2-positive biliary tract cancer (BTC) with an ORR of up to 52%. Inavolisib (Q3) Roche’s highly selective PI3Kα inhibitor for PIK3CA-mutated breast cancer. Asciminib (Q3) Novartis’ Bcr-Abl allosteric inhibitor for Philadelphia chromosome-positive chronic myeloid leukemia (CML). SHR-1701 (Q4) A PD-L1/TGF-βRII bifunctional fusion protein for first-line treatment of gastric cancer. Phase III study demonstrated significant extension in median overall survival. MRG003 (Q4) China’s first EGFR-targeting ADC with remarkable efficacy in nasopharyngeal carcinoma. Endocrinology and Metabolism: Tenapanor (Q1) The world’s only approved NHE3 inhibitor for controlling hyperphosphatemia in chronic kidney disease patients. Trend Analysis: Continued Innovation in Oncology: The emergence of multiple bispecific antibodies and ADC drugs is making targets and treatment options more precise and diverse. Breakthroughs in Autoimmune and Rare Diseases: New biologics are gradually addressing drug resistance and limited treatment options in previous therapies. Emergence of Domestic Innovative Drugs: Examples include SHR-1701 and MRG003, highlighting the growing research and development capabilities of Chinese pharmaceutical companies.   The sequential launch of these drugs will provide new therapeutic options for Chinese patients and enhance China’s position in the global pharmaceutical market.

An immunomodulatory startup called Nuvig Therapeutics announced a $161 million Series B amid rising competition to develop new and better autoimmune medicines. Nuvig, based in Menlo Park, CA, is working in the immunomodulatory pocket of the industry, hoping to develop new drugs that tamp down on unwieldy inflammatory diseases without the need for immunosuppression. The company, which is based on work out of Rockefeller University, broke cover with a $47 million Series A in May 2022. Sanofi, which has a pipeline heavily dependent on immunology, co-led the round with Blue Owl Healthcare Opportunities and Norwest Venture Partners. Bristol Myers Squibb and Novo Holdings chipped in again, and Bayer’s corporate venture arm — among other investment firms — joined as a new investor. Nuvig’s financing underscores the role that companies developing new treatments for autoimmune diseases now play in business development deals and startup fundraising rounds. Nuvig aims to limit the immune response on B cells and myeloid cells by upregulating a checkpoint receptor called Fc gamma R2B, chief scientific officer Pamela Conley said in an interview. Its candidates also expand T regulatory cells. “That’s somewhat unique in contrast to just an approach to lower all your IgG levels or wipe out your B cells or even certain T cell therapy approaches,” Conley said. “We believe that broad mechanism will allow us to have good activity across a wide range of autoimmune disease.” Conley co-founded Nuvig after serving as an executive at Portola Pharmaceuticals until Alexion bought the biotech for about $1.4 billion in 2020 . She initially led Nuvig as CEO and then handed the reigns to Julie Smith in early 2023. Smith “transitioned out of the company” this year, Conley said, and Nuvig is searching for a CEO who can take the company “beyond Phase 3.” The company’s lead asset, named NVG-2089, is a recombinant, Fc fragment immunomodulator that binds to type II Fc receptors. The 18-employee biotech is expected to enter Phase 2 in chronic inflammatory demyelinating polyneuropathy, or CIDP, “early next year,” Conley said. CIDP is a rare neurological and autoimmune disorder that impairs the sheaths that protect nerves. It impacts about five to seven people per 100,000 individuals. The company also plans to start a proof-of-concept trial in immune thrombocytopenia, or ITP, Conley said. The standard of care for CIDP and ITP is intravenous immunoglobulin, or IVIg, but patients have to take a large dose. It is a burdensome experience for patients with the chronic condition, Conley said. She said preclinical studies have shown Nuvig’s molecule is 10 to 20 times more potent than IVIg. The biotech also hopes for shorter infusions that take about an hour as compared to six to eight hours, according to Conley. NVG-2089 has been “very well-tolerated” so far in Phase 1, she said, noting the company doesn’t anticipate flu-like symptoms, headaches or other side effects because of the “large protein load that the patients have to endure” with IVIg. CIDP has attracted interest from multiple drugmakers in recent years. Both Takeda and argenx received FDA approvals for CIDP therapies this year. Sanofi also has a late-stage complement inhibitor called riliprubart, while Dianthus Therapeutics and Immunovant are in the clinic with CIDP treatment candidates. “The FcRn inhibitors — argenx has shown activity in CIDP — but their approach is to reduce your circulating IgG levels by 70% to 80%, which in the long run puts patients at risk for injection, just like many of the other approaches,” Conley said. “Complement inhibitors are also immunocompromising to some extent.” Beyond its lead program, Nuvig is exploring rheumatology, dermatology and neurology, Conley said.

AstraZeneca's bid to convert its anticoagulant reversal drug Andexxa (andexanet alfa) from accelerated to full approval faces headwinds after an FDA advisory committee raised safety and efficacy concerns during a meeting Thursday.The panel discussed data from ANNEXA-I, AstraZeneca's confirmatory trial that was stopped early last year after achieving superior haemostatic efficacy, the ability to limit the expansion of a potentially life-threatening bleed in the brain, versus usual care.However, FDA briefing documents released prior to Thursday's meeting highlighted "major safety findings," including a 14.6% thrombosis rate in the Andexxa arm compared with 6.9% in the control group, along with higher thrombosis-related deaths (2.5% vs 0.9%) at day 30.Moreover, FDA staff scientists noted that while the ANNEXA-I trial met its primary efficacy goal, results appeared to hinge mostly on one part of the composite endpoint: the size of the haematoma after 12 hours. Other important outcomes – such as neurologic status at 24 hours, modified Rankin Scale (mRS) at 30 days, and overall mortality – showed no difference between the study's two arms.The advisory panel, which did not vote on any formal questions, grappled with whether Andexxa's demonstrated benefits outweigh its risks. "We heard often this morning that better haemostasis leads to better outcomes, but it wasn't really evident in the numbers from the clinical trial – that patients that were treated with the andexanet have had worse outcomes in terms of neurological function, death and severe adverse events," noted panel member Sean Morrison."Yet all the physicians that we've heard from urged us to grant full approval suggesting that there's some advantage to andexanet beyond what was being measured in the clinical trial," he added.Meanwhile, panel member Rajiv Ratan said the reduction in haematoma volume seen in ANNEXA-I could be viewed as evidence that Andexxa is engaging its target, but he suggested that it hasn't demonstrated that this actually benefits patients in a meaningful way. "It doesn't seem like the change in haematoma volume – especially because it was relatively large for patients who are untreated – is enough as a primary endpoint."Andexxa was granted an accelerated approval by the FDA in 2018 as an antidote for the reversal of Factor Xa inhibitors. It was acquired by AstraZeneca in 2021 through its $39-billion Alexion, which itself acquired it from Portola Pharmaceuticals a year earlier for $1.4 billion. The drug generated sales of $182 million in 2023. This past January, AstraZeneca submitted a supplemental biologics application seeking to convert the accelerated approval into a full approval.