Akt-1 inhibitors(Serine/threonine-protein kinase AKT1 inhibitors), CLPP agonists(caseinolytic mitochondrial matrix peptidase proteolytic subunit agonists), D2 receptor antagonists(Dopamine D2 receptor antagonists)

Therapeutic Areas

NeoplasmsNervous System DiseasesOther Diseases+ [6]

Active Indication

Diffuse midline glioma, point mutation K27M in histone H3Diffuse Intrinsic Pontine GliomaRecurrent Glioma+ [18]

Inactive Indication

Advanced cancerAdvanced Colorectal AdenocarcinomaAdvanced Endometrial Carcinoma+ [23]

Originator Organization

Active Organization

+ [7]

Inactive Organization

The University of Texas MD Anderson Cancer Center

Icahn School of Medicine at Mount SinaiJonsson Comprehensive Cancer Center

+ [4]

License Organization

China Resources Sanjiu Medical & Pharmaceutical Co., Ltd.

Chimerix, Inc.

Ohara Pharmaceutical Co., Ltd.

+ [2]

Drug Highest PhaseApproved

First Approval Date

United States (06 Aug 2025),

Diffuse midline glioma, point mutation K27M in histone H3

RegulationPriority Review (United States), Fast Track (United States), Accelerated Approval (United States), Rare Pediatric Disease (United States), Orphan Drug (European Union), Orphan Drug (Australia)

Structure/Sequence

Molecular FormulaC24H26N4O

InChIKeyVLULRUCCHYVXOH-UHFFFAOYSA-N

CAS Registry1616632-77-9

Clinical Trials associated with Dordaviprone

NCT06012929

/ SuspendedPhase 2IIT

A Pilot Study, Open-Label Study of ONC201 for Refractory Meningioma

The goal of this clinical trial is to learn about treatment for a type of brain tumor called a meningioma. This study will enroll two groups of people. One group will be for people who will receive surgery to remove their brain tumor. The other group will be for people who have previously received treatment for their brain tumor but do not have any other available options for treatment.
The primary goals of this study are:
1. To measure how much of the study drug is present in tumor tissue taken from patients during surgery to remove their brain tumor
2. To measure the length of time between a study participant's first dose of study treatment until the time when their brain tumor gets worse or their death

Start Date01 Dec 2025

Sponsor / Collaborator

University of Nebraska

[+1]

NCT05630794

/ RecruitingPhase 1IIT

Phase 1 Trial of ONC201 for Chemoprevention in Colorectal Cancer

This phase I trial tests the safety, side effects, and best dose of ONC201 in preventing colorectal cancer in patients with familial adenomatous polyposis (FAP) or a history of multiple polyps. ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Start Date30 Jul 2025

Sponsor / Collaborator

National Cancer Institute

NCT04629209

/ WithdrawnPhase 2IIT

A Phase II, Open Label Study of ONC201 in Adults With EGFR-low Glioblastoma

This is an open-label, two arm study. The trial will enroll a total of up to 36 patients. Arm A will enroll up to a total of 6 evaluable patients and Arm B will enroll up to a total of 30 evaluable patients. Arm A will explore the intra-tumoral ONC201 concentrations and pharmacodynamic activity in adult EGFR-low glioblastoma patients. Arm B will determine the radiographic efficacy of ONC201 in adult recurrent EGFR-low glioblastoma patients. All patients will be treated with oral ONC201 (625 mg) twice weekly, 2 consecutive days on and 5 days off per week schedule.

Start Date28 Jun 2024

Sponsor / Collaborator

University of Minnesota Masonic Cancer Center

[+1]

100 Clinical Results associated with Dordaviprone

100 Translational Medicine associated with Dordaviprone

100 Patents (Medical) associated with Dordaviprone

261

Literatures (Medical) associated with Dordaviprone

01 Sep 2025·BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

A phase 1, randomized, crossover trial to assess the effect of itraconazole on the pharmacokinetics of dordaviprone in healthy adults

Article

Author: Morrison, Marion E. ; Mullin, Mark J. ; Faison, Shamia L. ; Batonga, Joelle ; Naderer, Odin ; Bartkus, Angela ; Arumugham, Thangam ; Tippin, Tim

Aims:

Dordaviprone (ONC201) is a novel, small molecule with antitumor efficacy in gliomas. The aim of this work was to evaluate the pharmacokinetics and safety of dordaviprone when given alone and when coadministered with a strong cytochrome P450 (CYP)3A4 inhibitor, itraconazole.

Methods:

In vitro human liver microsomes and recombinant human CYP enzyme assays were used to assess CYP‐mediated metabolism of dordaviprone. The clinical study was conducted in 18 healthy male and female participants as part of a larger 3 period open‐label, randomized, crossover bioequivalence and drug–drug interaction evaluation. Dordaviprone and metabolite ONC207 plasma concentrations were determined by validated liquid chromatography–tandem mass spectrometry methods.

Results:

In vitro assessments of CYP‐mediated dordaviprone metabolism indicated that CYP3A4 was the major CYP involved in the oxidation of dordaviprone. Accordingly, concomitant administration of dordaviprone with itraconazole significantly increased dordaviprone plasma maximum plasma concentration and area under the plasma concentration–time curve by 1.9 and 4.5‐fold, respectively, compared to dordaviprone alone. Treatment‐emergent adverse events were reported by 1 (5.6%) participant after receiving dordaviprone alone, and by 4 (22.2%) participants after receiving dordaviprone with itraconazole.

Conclusion:

Concomitant administration of dordaviprone with itraconazole significantly increased dordaviprone exposure confirming CYP3A4 is a major clearance pathway for dordaviprone. While dordaviprone was generally well tolerated when administered as a single 125‐mg dose with concomitant itraconazole, dose adjustment in patients receiving 625 mg dordaviprone with strong CYP3A4 inhibitors is warranted.

01 Sep 2025·DRUGS IN R&D

Effect of Severe Renal Impairment on Dordaviprone (ONC201) Pharmacokinetics

Article

Author: Faison, Shamia L ; Morrison, Marion E ; Batonga, Joelle ; Naderer, Odin ; Mullin, Mark J ; Bartkus, Angela ; Arumugham, Thangam ; Tippin, Tim

BACKGROUND AND OBJECTIVE:

Dordaviprone (ONC201) is a novel small molecule with antitumor effects in patients with glioma. The major elimination pathway of dordaviprone is metabolism via cytochrome P450 (CYP) 3A4. This study was designed to assess the effect of severe renal impairment (RI) on dordaviprone pharmacokinetics.

METHODS:

Eight participants with severe RI and eight participants matched for age, body mass index, and sex, with normal renal function, received a single oral 375-mg dose of dordaviprone. Plasma and urine samples were analyzed for dordaviprone using validated liquid chromatography tandem mass spectrometry methods. Plasma and urine pharmacokinetics, plasma protein binding, and safety profiles were evaluated.

RESULTS:

Dordaviprone exposure was increased in participants with severe RI. Geometric mean ratios (90% confidence intervals) of the severe RI cohort compared with the healthy matched cohort were 1.13 (0.92-1.39), 1.48 (0.98-2.23), and 1.47 (0.97-2.21), for maximum concentration (C_max), area under the plasma concentration-time curve from time zero to time of last measurable plasma concentration (AUC_last), and AUC from time zero to infinity (AUC_inf), respectively. Renal clearance of dordaviprone was negligible and similar in both cohorts. Plasma protein binding was similar in both cohorts, leading to similar increases in unbound dordaviprone C_max and AUC in severe RI versus healthy participants. All dordaviprone-related adverse events were mild, occurring in 50% of participants with severe RI and 37.5% of healthy matched participants.

CONCLUSIONS:

Despite its minimal renal clearance, dordaviprone geometric mean AUC was increased by ~50% in severe RI participants, suggesting CYP3A4 activity may have been suppressed in these participants. The results of this study will be used to inform dordaviprone dosing in patients with RI.

TRIAL REGISTRATION NUMBER:

ACTRN12622000405718; Registered on March 9, 2022. Key Points Dordaviprone is a small molecule drug candidate for the treatment of glioma and is eliminated by non-renal mechanisms. In this clinical trial performed in severely renal-impaired participants, dordaviprone plasma concentrations were increased relative to those observed in healthy participants. This result suggests that the metabolic enzyme activity of CYP3A4 was reduced in severely renal-impaired participants.

01 Jul 2025·Clinical Pharmacology in Drug Development

A Phase 1 Study to Evaluate the Absorption, Metabolism, and Disposition of Dordaviprone in Healthy Adult Participants

Article

Author: Mullin, Mark J. ; Faison, Shamia L. ; Morrison, Marion ; Bartkus, Angela ; Naderer, Odin ; Tippin, Tim ; de Castro, Francine A. ; Teffera, Yohannes

Abstract:

Dordaviprone (ONC201) is a novel, small‐molecule imipridone with antitumor activity in patients with a glioma. Six healthy male participants received a single 625‐mg (100‐µCi) oral dose of [14C]‐dordaviprone. Blood, plasma, urine, and feces were collected up to 288 hours after dosing and analyzed by liquid scintillation counting. Metabolite profiles were evaluated using liquid chromatography‐radiometric detection, and metabolite identification was accomplished by liquid chromatography with tandem mass spectrometry. Concentrations of drug‐derived radioactivity in blood and plasma peaked at 1 hour after dosing and were below the limit of quantitation by 72 hours (whole blood) to 96 hours (plasma) after dosing. Seventy‐one percent of the administered radioactivity was recovered in urine and 20% in feces. In plasma, the major circulating compounds were dordaviprone and the inactive metabolite ONC207, each contributing approximately one third of the total radioactivity area under the curve. Of the 19 metabolites identified in plasma, no other single metabolite contributed more than 10% to the total radioactivity area under the curve. Unchanged dordaviprone was a minor component in excreta (less than 0.3%), with multiple metabolites identified in urine and feces. Given the lack of dordaviprone in excreta and the metabolites formed, the primary route for dordaviprone elimination was through urinary excretion of oxidative metabolites.

138

News (Medical) associated with Dordaviprone

09 Sep 2025

·investor.jazzpharma.com

Modeyso™ (dordaviprone) Included in National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology for H3 K27M-mutant Diffuse Glioma

Modeyso, the first treatment option for this ultra-rare and aggressive brain tumor, is commercially available in the United States For U.S. media and investors only DUBLIN , Sept. 9, 2025 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that Modeyso™ (dordaviprone) is recommended by the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a category 2A single-agent treatment option for pediatric and adult patients with recurrent or progressive diffuse high-grade glioma harboring an H3 K27M mutation. Modeyso was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on August 6, 2025 for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in the Phase 3 ACTION confirmatory trial.1 "The rapid addition of Modeyso to the NCCN Guidelines® – in both the Pediatric Central Nervous System Cancers and Central Nervous System Cancers guidelines – reflects the urgency of the unmet need that patients are faced with when diagnosed with this devastating and aggressive brain tumor," said Kelvin Tan, MB BCh, MRCPCH, chief medical affairs officer of Jazz Pharmaceuticals . "We are proud to bring Modeyso to patients in the U.S. as the first treatment option for recurrent H3 K27M-mutant diffuse midline glioma, representing a meaningful shift in the treatment landscape for patients and their families." The NCCN Guidelines® play a pivotal role in decision-making processes for individuals involved in cancer care all over the world, including physicians, nurses, pharmacists, payers, and patients and their families. The guidelines present expert recommendations for cancer screening, diagnosis and treatment, as well as cancer care options, and are utilized in cancer treatment decision-making to drive positive patient outcomes. NCCN is a not-for-profit alliance of 33 leading cancer centers devoted to patient care, research and education. NCCN is dedicated to defining and advancing effective, equitable, accessible and quality cancer care and prevention so all people can live better lives. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. The FDA approval of Modeyso was based on an integrated efficacy analysis of 50 patients with recurrent H3 K27M-mutant diffuse midline glioma, selected from five open-label clinical studies based on pre-specified eligibility criteria. The overall response rate (ORR), as assessed by blinded independent central review (BICR) using Response Assessment in Neuro-Oncology (RANO) 2.0 criteria, was 22% (95% CI: 12 to 36), with an additional responder identified by integrated RANO 2.0. Among responders, the median duration of response was 10.3 months (95% CI: 7.3 to 15.2), with 73% maintaining their response for at least six months and 27% for at least 12 months.1 The safety of Modeyso was evaluated in 376 adult and pediatric patients with glioma across four open-label clinical studies. Serious adverse reactions occurred in 33% of patients. Serious adverse reactions reported in more than 2% of patients included hydrocephalus (5%), vomiting (4.3%), headache (3.2%), seizure (2.4%) and muscular weakness (2.1%). The most common adverse reactions in patients who received Modeyso (≥20%) were fatigue, headache, vomiting, nausea and musculoskeletal pain.1 See additional safety information below and full prescribing information: https://pp.jazzpharma.com/pi/modeyso.en.USPI.pdf About H3 K27M-Mutant Diffuse Midline Glioma H3 K27M-mutant diffuse midline glioma is a rare and highly aggressive brain tumor that primarily affects the midline structures of the brain and spinal cord.2,3 It is characterized by a specific genetic mutation (H3 K27M) that disrupts epigenetic regulation and drives tumor growth.4 Most commonly diagnosed in children and young adults, patients with this type of glioma often face an extremely poor prognosis, with limited therapeutic options and very low survival rates following recurrence.5 Median survival is approximately one year from diagnosis and less than six months after disease progression following frontline therapy.5 About Modeyso™ (dordaviprone) Modeyso (dordaviprone) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.1 Modeyso is an orally administered small molecule given once weekly. Modeyso is a protease activator of the mitochondrial caseinolytic protease P (ClpP) and also inhibits dopamine D2 receptor (DRD2). In vitro, dordaviprone activates the integrated stress response, induces apoptosis and alters mitochondrial metabolism, leading to restored histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma.1 Modeyso received accelerated approval based on a pre-specified integrated efficacy analysis of 50 adult and pediatric patients with recurrent H3 K27M-mutant diffuse midline glioma enrolled across five open-label clinical studies (ONC006, ONC013, ONC014, ONC016 and ONC018). Continued approval may be contingent upon verification and description of clinical benefit in the ongoing Phase 3 ACTION trial (NCT05580562), which is evaluating the safety and clinical benefit of Modeyso in newly diagnosed patients with H3 K27M-mutant diffuse glioma following radiotherapy.4 Modeyso was developed by Chimerix prior to its acquisition by Jazz Pharmaceuticals in April 2025 . Modeyso (dordaviprone) is not approved anywhere else in the world. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS HypersensitivityMODEYSO can cause severe hypersensitivity reactions. In the pooled safety population, Grade 3 hypersensitivity reactions occurred in 0.3% of patients receiving MODEYSO. Signs and symptoms of hypersensitivity may include rash, hives, fever, low blood pressure, wheezing, or swelling of the face or throat. Inform patients about the signs and symptoms of hypersensitivity reactions and instruct them to seek immediate medical attention if symptoms occur. If clinically significant hypersensitivity or anaphylaxis occur, immediately interrupt MODEYSO and initiate appropriate medical treatment and supportive care. Based on the severity of the adverse reaction, temporarily interrupt or permanently discontinue MODEYSO. QTc Interval ProlongationMODEYSO causes concentration-dependent QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (e.g. torsades de pointes) or sudden death. In patients who received MODEYSO and underwent at least one post baseline ECG, QTcF increase of >60 msec compared to baseline and QTcF >500 msec occurred in 6% and 1.2% of patients, respectively. Monitor ECGs and electrolytes prior to initiation and periodically during treatment, as clinically indicated. Increase the frequency of monitoring in patients with congenital long QT syndrome, existing QTc prolongation, a history of ventricular arrhythmias, electrolyte abnormalities, heart failure, or who are taking strong or moderate CYP3A4 inhibitors. Avoid concomitant use with other agents known to prolong the QT interval. If concomitant use cannot be avoided, increase the frequency of monitoring and separate administration of MODEYSO and QT-prolonging product. Interrupt or reduce the dose of MODEYSO in patients who develop QT prolongation; permanently discontinue in patients with signs of life-threatening arrhythmias. Embryo-Fetal Toxicity MODEYSO can cause fetal harm when administered to a pregnant woman.Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with MODEYSO and for 1 month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with MODEYSO and for 1 month after the last dose ADVERSE REACTIONSSerious adverse reactions occurred in 33% of the 376 patients who received MODEYSO. Serious adverse reactions in >2% of patients included hydrocephalus (5%), vomiting (4.3%), headache (3.2%), seizure (2.4%), and muscular weakness (2.1%). Fatal adverse reactions occurred in 1% of patients who received MODEYSO, including cardiac arrest (0.5%), intracranial hemorrhage (0.3%), and encephalopathy (0.3%). The most common adverse reactions (≥20%) reported in clinical trials with MODEYSO were fatigue (34%), headache (32%), vomiting (24%), nausea (24%), and musculoskeletal pain (20%). The most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (7%), decreased calcium (2.7%), and increased alanine aminotransferase (2.4%). DRUG INTERACTIONS Strong and Moderate CYP3A4 Inhibitors Avoid concomitant use of MODEYSO with strong and moderate CYP3A4 inhibitors. If concomitant use cannot be avoided, reduce the MODEYSO dose as recommended and monitor for toxicity. Strong and Moderate CYP3A4 Inducers Avoid concomitant use of strong and moderate CYP3A4 inducers with MODEYSO. USE IN SPECIFIC POPULATIONS LactationThere are no data on the presence of MODEYSO in human milk because of the potential for serious adverse reactions from MODEYSO in breastfed children, advise women not to breastfeed during treatment with MODEYSO and for 1 week after the last dose. Pediatric UseThe safety and effectiveness of MODEYSO have not been established in patients less than 1 year of age. Dosing has not been established for patients weighing less than 22 pounds (10 kg). Please refer to the full Prescribing Information, including both Patient Information and Instructions for Use, for complete safety and administration information. About Jazz Pharmaceuticals Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing potentially life-changing medicines for people with serious diseases – often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit www.jazzpharmaceuticals.com for more information. Contacts:Media: Kristin Bhavnani Head of Global Corporate Communications Jazz Pharmaceuticals plc CorporateAffairsMediaInfo@jazzpharma.comIreland +353 1 637 2141 U.S. +1 215 867 4948 Investors: Jack Spinks Executive Director, Investor Relations Jazz Pharmaceuticals plc investorinfo@jazzpharma.com Ireland +353 1 634 3211 U.S. +1 650 496 2717 1 MODEYSO (dordaviprone) Prescribing Information. Palo Alto, CA : Jazz Pharmaceuticals, Inc. 2 Yang, Z., Sun, L., Chen, et al. New progress in the treatment of diffuse midline glioma with H3K27M alteration. Heliyon. 2024;10(2).3 National Cancer Institute . Diffuse Midline Glioma: Diagnosis and Treatment. Updated August 20, 2024 . Accessed September 8, 2025 . https://www.cancer.gov/rare-brain-spine-tumor/tumors/diffuse-midline-gliomas4 ClinicalTrials.gov. ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) (ACTION). Updated August 26, 2025 . Accessed September 8, 2025 . Study Details | ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) | ClinicalTrials.gov5 Bagley, S. J., Umemura, et al. Prognostic Features of Recurrent Midline and H3 K27M-Mutant Glioma. Cancers. 2025;17(13):2107. https://doi.org/10.3390/cancers17132107 View original content to download multimedia:https://www.prnewswire.com/news-releases/modeyso-dordaviprone-included-in-national-comprehensive-cancer-network-nccn-clinical-practice-guidelines-in-oncology-for-h3-k27m-mutant-diffuse-glioma-302549794.html SOURCE Jazz Pharmaceuticals plc

Drug ApprovalClinical ResultPhase 3Accelerated ApprovalAcquisition

02 Sep 2025

·www.biospace.com

Rare Diseases Secure Four FDA Firsts in August

Pictured: FDA Headquarters, iStock, Grandbrothers iStock, Grandbrothers Aside from the rare disease market, Novo Nordisk also scored a key regulatory win last month for its blockbuster GLP-1 drug Wegovy, which can now be used to treat patients with metabolic dysfunction-associated steatohepatitis. August was a big month for the rare disease space, which saw four history-making approvals—though the streak was marred by one rejection. Also walking away with a win last month was Novo Nordisk, which secured a critical label expansion that, according to analysts, could help its blockbuster GLP-1 medication gain access to nearly $2 billion in added peak sales. Read below for more. Four Firsts for Rare Diseases Company: Jazz Pharmaceuticals Drug: Modeyso Indication: Glioma The first rare disease nod came on Aug. 6 for Jazz Pharmaceuticals’ dordaviprone, which was approved for patients aged 1 year and above with diffuse midline glioma with an H3 K27M mutation who have progressed after prior treatments. The drug, which will carry the brand name Modeyso, is the first systemic therapy for this specific type of glioma, according to the FDA’s announcement of the approval. Modeyso was approved under the FDA’s accelerated pathway, supported by overall response (OR) data from a pair of Phase I and Phase II studies. According to Jazz’s news release announcing the approval, Modeyso achieved an OR of 22% in 50 adult and pediatric patients. Among responders, median duration was 10.3 months. To maintain Modeyso’s approval, Jazz is running a confirmatory Phase III trial that is expected to be complete in August 2026. Company: Insmed Drug: Brinsupri Indication: Non-cystic fibrosis bronchiectasis Not a week after Jazz, Insmed secured an FDA nod for brensocatib—now sold as Brinsupri—for the rare respiratory disorser non-cystic fibrosis bronchiectasis. Brinsupri, taken orally once daily, is indicated for patients aged 12 years and up. Insmed has set its price at $88,000 per year—“a little higher” than what analysts were expecting, Guggenheim Partners wrote at the time. Brinsupri marks two firsts for the biopharma industry: Not only is it the first drug for bronchiectasis to reach the market, but it is also the first approved treatment that works by blocking DPP1, an enzyme that plays a role in activating the inflammatory response in airways. Brinsupri is backed by data from the Phase III ASPEN trial. Data published in The New England Journal of Medicine in April showed that Brinsupri lowered the rate of pulmonary exacerbations by around 20% versus placebo. The Phase II WILLOW trial also supported Brinsupri’s approval, demonstrating a roughly 40% reduction in the risk of exacerbations relative to placebo. Company: Precigen Drug: Papzimeos Indication: Recurrent respiratory papillomatosis Then, on Aug. 14, Precigen won the FDA’s go-ahead for zopapogene imadenovec-drba, now named Papzimeos, for the treatment of recurrent respiratory papillomatosis (RRP). In its announcement of the approval, the FDA said Papzimeos is a “first-of-its-kind” non-replicating immunotherapy for this disease. With around 1,000 new cases in the U.S. annually, RRP is a rare disease that manifests as benign tumors in the airways, leading to difficulties in swallowing and breathing. If left unchecked, RRP can lead to death. Papzimeos works by helping the body mount an immune response against cells infected by HPV 6 and HPV 11, both associated with RRP. Pivotal Phase I/II data supported Papzimeos’ approval, showing that the biologic elicited a complete response rate of more than 50% in treated patients, while over 85% needed fewer surgical interventions in the year after treatment. Company: Ionis Pharmaceuticals Drug: Dawnzera Indication: Hereditary angioedema Capping off the rare disease rally this month is Ionis Pharmaceuticals. On Aug. 22, the California biotech’s antisense oligonucleotide donidalorsen, now branded Dawnzera, became the industry’s first RNA-targeting prophylactic for hereditary angioedema (HAE). Patients 12 years and older can receive the therapy, which is given via a subcutaneous injection every four weeks. Dawnzera targets the prekallikrein mRNA, causing its destruction. This, in turn, reduces overall levels of PKK, a protein that plays a role in swelling and pain attacks in HAE. Data from the OASIS-HAE study backed Thursday’s approval, demonstrating an 81% reduction in HAE attack rate versus placebo over 24 weeks of observation. Results were published May 2024 in the New England Journal of Medicine and additionally showed a significant improvement in patients’ quality of life. Wegovy Win For Novo On Aug. 15, the FDA gave the go-ahead for Novo Nordisk’s blockbuster injection Wegovy to be used in adults with metabolic dysfunction-associated steatohepatitis. The GLP-1 drug, indicated for patients with moderate to advanced liver scarring but without cirrhosis, should be used in conjunction with a reduced-calorie diet and higher physical activity. Wegovy’s approval in MASH is a “step in the right direction” for Novo, analysts at BMO Capital Markets wrote in an Aug. 17 note to investors, adding that breaking into the MASH market “could start to help shift the momentum” for Wegovy, which in the first half of 2025 has been hit hard by the rise of compounders. BMO anticipates peak MASH sales of $1.9 billion for Wegovy. Data from the Phase III ESSENCE trial, which supported the label expansion, showed that Wegovy improved liver fibrosis without worsening steatohepatitis in 37% of treated patients at 72 weeks, versus 22.5% in placebo comparitors. At the same time, Wegovy resolved steatohepatitis without worsening fibrosis in 62.9% of patients, as compared with 34.1% of placebo participants. Wegovy has “clear efficacy in MASH,” the BMO analysts wrote, adding that its “clean safety pro broad benefits across metabolic disease” could help establish the drug “as a backbone treatment for MASH.” Wegovy joins Madrigal Pharmaceuticals’ Rezdiffra in the MASH space. Approved in March 2024 , Rezdiffra made $180.1 million last year. Three COVID-19 Vaccines Cleared, With Restrictions The FDA on Aug. 27 approved updated COVID-19 vaccines from Pfizer, Moderna and Novavax, but with key limitations: The shots can only be used in adults 65 years and older and younger people who are at elevated risk of severe outcomes. There are some minor differences across the three, particularly as it pertains to use in the at-risk younger population. Novavax’s Nuvaxovid, a protein-based shot, is authorized for individuals 12 through 64 years. Pfizer and BioNTech’s mRNA-based Comirnaty can be given to children as young as 5 years. Moderna’s mNEXSPIKE is indicated for people 12 through 64 years, while Spikevax is indicated for individuals 6 months through 64 years. Both vaccines are mRNA-based. These approvals come after Health Secretary Robert F. Kennedy Jr. in May removed routine COVID-19 vaccination for healthy children and healthy pregnant women from CDC recommendations. PTC Hit With Rejection in Friedreich’s Ataxia The FDA on Aug. 19 turned down PTC Therapeutics’ vatiquinone, which the company has proposed for the treatment of Friedreich’s ataxia in children and adults. In its complete response letter, the FDA stated that “substantial evidence of efficacy was not demonstrated” and that PTC would need an additional “adequate and well-controlled study” to support a resubmission. Matthew Klein, the company’s CEO, said in a statement at the time that PTC is planning to meet with the FDA to discuss potential next steps. Vataquinone is a small molecule that blocks some of the cellular pathways that go awry in patients with frataxin mutations, the underlying cause of Friedreich’s ataxia. Patients with this rare neuromuscular disease suffer from loss of coordination and muscle strength, as well as difficulty speaking, swallowing and breathing. Around 25,000 patients have been diagnosed worldwide, according to PTC. Vataquinone missed the mark in a Phase III, registration-directed trial back in 2023, failing to meet its primary endpoint of improving gait, stability and limb function after 72 weeks. PTC sought registration with the FDA based on secondary outcomes such as stability.

Clinical ResultDrug ApprovalPhase 3Phase 2Vaccine

22 Aug 2025

·www.biospace.com

Ionis Wins Approval For First RNA-Targeted Prophylactic for Rare Swelling Disease

iStock, Softulka The drug, for hereditary angioedema, is Ionis’ second wholly owned asset. The FDA on Thursday approved Ionis Pharmaceuticals’ donidalorsen for the prevention of disease attacks in patients with hereditary angioedema. The product will carry the brand name Dawnzera. Dawnzera is the first and so far only RNA-targeting therapy approved as a prophylactic treatment for hereditary angioedema (HAE), Ionis said in its Thursday news release . The product, which can be used in patients 12 years and above, will launch in the U.S. in the coming days. “We see Dawnzera’s pro superior to current prophylactic options, with less frequent dosing and at-home auto-injector dosing being further differentiators,” William Blair analysts told investors in a Thursday note, adding that Dawnzera marks Ionis’ second wholly owned asset. “We view Dawnzera as a highly competitive HAE prophylactic.” Data from the OASIS-HAE study backed Thursday’s approval. Results published in the New England Journal of Medicine in May 2024 showed that over 24 weeks of follow-up, the RNA-targeted therapy lowered the monthly HAE attack rate by 81% versus placebo. Dawnzera also demonstrated an approximately 90% reduction in moderate-to-severe HAE attacks over 24 weeks when measured from the second dose, and significantly improved patients’ quality of life. Ionis filed data from the Phase III OASISplus open-label extension study to bolster its application. According to Thursday’s release, Dawnzera treatment resulted in a 94% drop in the total mean attack rate from baseline at one year of follow-up. Meanwhile, a readout last month demonstrated that patients who switched to the RNA-targeting therapy from other prophylactics did so without experiencing spikes in attacks. In a survey, 84% of patients indicated that they preferred Dawnzera over their previous prophylactic. Administered subcutaneously every four weeks, Dawnzera is a conjugated antisense oligonucleotide that targets the prekallikrein mRNA, causing its destruction. This reduces overall levels of PKK, a protein that plays a role in swelling and pain attacks in HAE. Dawnzera does not come with a boxed warning, though its label has precautions for hypersensitivity reactions such as anaphylaxis. Dawnzera’s approval on Thursday continues a series of history-making approvals for the rare disease space this month. Leading the pack is Jazz Pharmaceuticals, which on Aug. 6 won the FDA’s go-ahead for dordaviprone, now marketed as Modeyso, for the treatment of diffuse midline glioma with an H3 K27M mutation in patients aged one year and up who have progressed after previous interventions. Modeyso is the first drug approved for this ultrarare brain tumor. A week later, Insmed’s brensocatib won approval for non-cystic fibrosis bronchiectasis for patients 12 and over. The drug, branded as Brinsupri, is the first therapy approved for this indication and is also the first DPP1 inhibitor to win the FDA’s blessing. Finally, Precigen on Aug. 14 bagged the industry’s first immunotherapy approval for recurrent respiratory papillomatosis with zopapogene imadenovec-drba, which will carry the brand name Papzimeos.

Clinical ResultDrug ApprovalPhase 3ImmunotherapyOligonucleotide

100 Deals associated with Dordaviprone

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KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14844

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Diffuse midline glioma, point mutation K27M in histone H3	United States	Chimerix, Inc.	06 Aug 2025

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diffuse Intrinsic Pontine Glioma	Phase 3	Denmark	Chimerix, Inc.	29 Sep 2022
Diffuse Intrinsic Pontine Glioma	Phase 3	France	Chimerix, Inc.	29 Sep 2022
Diffuse Intrinsic Pontine Glioma	Phase 3	Spain	Chimerix, Inc.	29 Sep 2022
Diffuse Intrinsic Pontine Glioma	Phase 3	Sweden	Chimerix, Inc.	29 Sep 2022
Meningioma	Phase 2	United States	Chimerix, Inc.	01 Dec 2025
Recurrent Glioma	Phase 2	United States	The University of California, San Francisco	20 Oct 2021
Recurrent Glioma	Phase 2	Australia	The University of California, San Francisco	20 Oct 2021
Recurrent Glioma	Phase 2	Israel	The University of California, San Francisco	20 Oct 2021
Recurrent Glioma	Phase 2	Netherlands	The University of California, San Francisco	20 Oct 2021
Recurrent Glioma	Phase 2	New Zealand	The University of California, San Francisco	20 Oct 2021

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03416530 \| NCT03295396 \| NCT05392374 \| NCT03134131 \| NCT02525692 (ONC018, FDA) Manual	Phase 1	Diffuse midline glioma, point mutation K27M in histone H3 H3 K27M-mutant	50	Dordaviprone	isjidljkxv(keuqyedufr) = minckaroxd cpqhtwlajb (rcvulekwtr, 12 - 36) View more	Positive	06 Aug 2025
NCT03295396 (ACTR-34 \| ONC013, CTgov)	Phase 2	Diffuse midline glioma, point mutation K27M in histone H3 \| Recurrent Malignant Glioma	73	Dordaviprone (Arm A)	nsmgyrqdhq = mcsrcngble zrgyuajasz (ojmdwrzpre, cmljumwdaf - bzrmtedixx) View more	-	28 Jul 2025
				Dordaviprone (Arm B)	nsmgyrqdhq = wophdtjqyr zrgyuajasz (ojmdwrzpre, kmzprkzspd - ftsnswesxl) View more
NCT03416530 \| NCT03295396 (ONC013 (Arm B) and ONC014 (Arm F), ASCO2025)	Phase 1/2	Diffuse midline glioma, point mutation K27M in histone H3 H3 K27M-mutant	41	Dordaviprone (ONC201) 625 mg	fqxrdvgfmy(aionhaejgg) = elbgfczbaj ewtisdexyy (kulsluqjkw, 5.6 - 34.7) View more	Positive	30 May 2025
				Dordaviprone (ONC201) dose scaled by body weight	fqxrdvgfmy(aionhaejgg) = yfyeelwdfj ewtisdexyy (kulsluqjkw ) View more
NCT02525692 (PATH-25 \| ACTR-51 \| ONC006, CTgov)	Phase 2	Diffuse midline glioma, point mutation K27M in histone H3 \| Basal Ganglia Diseases \| Recurrent Glioblastoma	84	Dordaviprone (ONC201) (Arm A)	wvsukomcpo = llgdmgwnpf gmjvvmuckr (yuypopnlyx, fcjqtxfsaz - sjajoetfbj) View more	-	24 Dec 2024
				Dordaviprone (Arm B)	wvsukomcpo = krrlapwfjm gmjvvmuckr (yuypopnlyx, quyheepemt - qigiiociir) View more
NCT03485729 (CTgov)	Phase 2	Recurrent Endometrial Cancer	27	Dordaviprone (Arm B)	yjisuaqvkm = bkejrpatqu fsdihtsqgj (ksduxzniod, wbygeaulaj - kkefywhznh) View more	-	24 Dec 2024
				Dordaviprone (Arm A)	soksypvdhz(bdfdtublzu) = fgwejpmntc dsgepbtpov (wplkxikikh, vnaearxxkb - vnyziiafug) View more
NCT03034200 (CTgov)	Phase 2	Neuroendocrine Tumors \| Pheochromocytoma	30	ONC201 (Arm A: Metastatic PC-PG)	xnspuictqu(nfarqttvxr) = umbchcvyuk psnuouktad (wckbbnhnxs, rahdtjoyfd - xqaoxofthg) View more	-	26 Nov 2024
				ONC201 (Arm B: Other NETs)	xnspuictqu(nfarqttvxr) = ukhzcaqdkr psnuouktad (wckbbnhnxs, sqfqttjnpr - hzolawpuzq) View more
CTNI-54 (SNO2024)	Not Applicable	Diffuse midline glioma, point mutation K27M in histone H3 H3K27M-mutant	-	ONC201 (DORDAVIPRONE)	nkczntbrnt(vtvpjebjpz) = cdwxekeunq dwfjpjbxjm (ngthkgotht, 15 - 41) View more	Positive	11 Nov 2024
NCT05580562 (ACTION, ASTRO2024)	Phase 3	Diffuse midline glioma, point mutation K27M in histone H3	50	ONC201	balvkbwvlm(cxcgzxsfdp) = pgjqckruky moeliijloj (bzjlwdspsk )	Positive	01 Oct 2024
				Standard Radiotherapy Dosing Regimens	balvkbwvlm(cxcgzxsfdp) = lvgczxyyhw moeliijloj (bzjlwdspsk )
NCT02863991 (CTgov)	Phase 1/2	Relapse multiple myeloma	17	Dexamethasone+ONC201 (Phase 1: 375 mg ONC201 + 20 mg Dexamethasone)	wlmbdcbdff = xzvpjatlbn hfkozwkrsl (dolqtsaxlf, fflyltljci - snotnsqjnp) View more	-	03 Jul 2024
				Dexamethasone+ONC201 (Phase 2: 625 mg ONC201 + 20 mg Dexamethasone)	wlmbdcbdff = mdrqiwbibr hfkozwkrsl (dolqtsaxlf, fihunmljdn - xttfnxotpt) View more
NCT05009992 (Biospace) Manual	Phase 2	Diffuse Midline Glioma First line	132	paxalisib in combination with ONC201 (Cohort 1)	flzwwofmqr(ojlgcryxfj) = izlfljwmlc ywjpamvilr (xqryvalaif )	Positive	27 Jun 2024
				paxalisib in combination with ONC201 (Cohort 2)	flzwwofmqr(ojlgcryxfj) = sxmzvbyihs ywjpamvilr (xqryvalaif )

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