Dordaviprone

Brain tumor medical poster. Cancer, metastasis or benign in the human head or in the nerves, pituitary gland, pineal gland, and membranes that cover the surface of the brain 3D vector illustration iStock, Pikovit44 The medium-sized biopharma is showing off new results from dordaviprone and Zepzelca, both of which were acquired through Jazz Pharmaceuticals’ dealmaking over the last five years. Rob Iannone showed me the ASCO 2025 name tag he’s wearing. Below the line where it says “Jazz Pharmaceuticals” is a big yellow stripe announcing that Iannone has been a member of the American Society of Clinical Oncology for a quarter of a century. “I’ve been coming to ASCO for 25 years; that gives you a hint about my age,” he says with a sly smile. When he began attending the annual meeting in 2000, Iannone was a pediatric oncologist. “In that time, I’ve treated patients with high-grade gliomas. Debulking surgeries and radiation therapy was standard of care back then,” he said. “Here we are 25 years later, and the standard of care is debulking surgery and radiation.” Iannone, chief medical officer at California-based Jazz, is hoping that a new molecule might change that. Acquired in Jazz’s $935 million buy-out of Chimerix in March, dordaviprone is a multi-target small molecule for pediatric gliomas, a particularly aggressive and deadly brain cancer. Jazz was intrigued enough to pay a 72% premium on Chimerix’s stock to get its hands on the molecule, which has an FDA PDUFA date of August 18. Jazz is at ASCO to present, among other things, new efficacy and safety data from a Phase II trial of dordaviprone. While the drug’s specific indication (H3K27 mutated gliomas) is rare—affecting around 5,000 patients worldwide, according to Truist analysts writing at the time of the Chimerix deal— the potential applicability of the dordaviprone is much broader. Truist modeled a potential $800 million in yearly sales by 2037 for the drug, and noted that its mechanism of action might make it valuable for other cancers beyond gliomas. The Chimerix deal also brought with it a next-generation version of dordaviprone, termed ONC206, with a similar mechanism and higher potency in vitro . Iannone said he is chuffed with the results of the acquisition, noting that it “fits in well” with Jazz’s overall pipeline strategy of looking for areas of unmet needs. And Jazz is a good fit for effectively bringing dordaviprone and its successor to the market, Iannone said. Earlier in his career, Iannone bounced from a professorship in pediatrics, oncology and bone marrow transplantation at the University of Pennsylvania to work at Merck, where he contributed to the development of the mega blockbuster Keytruda. “I was at the right place at the right time” he said about his time on that project. He then had stints at AstraZeneca and Immunomedics before coming to Jazz six years ago. Compared to the tens of thousands of employees marshalled by Merck and AstraZeneca, Jazz employs a modest 3,000–3,500 people, about 800 of which are in research and development. “We are a little bit of a Goldilocks size,” Iannone said. “We have all the resources we need to accomplish our goals. We’re small enough that we don’t get in our own way. That makes us a favorable partnership, people are surprised at we can do as partners.” He noted ease of access as one example. “When we’re discussing acquisitions or licensing, companies have direct access to people like me, which might be harder at a bigger company.” That ease of liaising with other companies has brought Jazz some of its lead molecules, Iannone said. Notably, Jazz licensed its small molecule therapeutic Zepzelca from PharmaMar in 2021 for a scant $5 million up front plus up to $3 million in sales milestones, as well as tiered royalties. In addition to its presentation on dordaviprone, Jazz is in Chicago this week to present new data from the Phase III IMforte trial of Zepzelca in combination with Roche’s Tecentriq in small cell lung cancer. Adding Zepzelca to Roche’s PD-1 inhbitor improved patients’ median survival by four months compared with Tecentriq alone (17 months versus 13 months, according to Iannone), while reducing patients’ risk of death by 27%. Most encouraging was a tolerable safety profile. The combo regimen mostly resulted in neutropenia, which Iannone said can be managed and is a solid trade-off for patients who would otherwise face a rough chemotherapy regimen. The usual treatment regimen involves four to six cycles of chemo, Iannone explained. “Most patients don’t make it to six, maybe they get to four. Toxicity is such that patients stop, and potentially continue on with anti-PD-1 therapy alone. Survival after patients stop chemo drops rapidly, Iannone added. Results from IMforte indicate that Zepzelca could represent a more palatable option. The companies have already filed a BLA for the combo but the FDA has yet to set a PDUFA date. With the new survival data in hand, “I’d expect to get priority review, which would allow us to get an approval this year,” Iannone said.

The FDA has granted a third approval for WELIREG, authorizing its use as a treatment for patients with rare endocrine system tumors known as pheochromocytoma or paraganglioma (PPGL). This approval applies to individuals aged 12 and older with locally advanced, unresectable, or metastatic PPGL, making WELIREG the first oral therapy available for advanced cases of the disease. LAS VEGAS, May 28, 2025 /PRNewswire/ -- Pheochromocytomas and paragangliomas (PCPG) are highly vascular neuroendocrine tumors originating from chromaffin cells of the adrenal medulla or from neural crest-derived cells located outside the adrenal glands. These tumors are categorized based on their location, either in the adrenal medulla or in extra-adrenal paraganglia. They arise from sympathetic tissues found in the adrenal glands or along the abdomen, or from parasympathetic tissues in areas such as the head, neck, and thorax. Sympathetic tumors often secrete large quantities of catecholamines and are found in the adrenal medulla in about 80% of cases. The remaining 20% are extra-adrenal, typically located along the prevertebral and paravertebral sympathetic ganglia in the chest, abdomen, or pelvis. In 2024, there were 4,900 incident PCPG cases across the 7MM, with numbers expected to rise in the coming years. Although significant progress has been made in understanding these tumors, accurately predicting their malignancy remains challenging in the absence of detectable metastases. Surgical resection remains the primary treatment for most localized PCPGs when feasible. In cases of advanced or metastatic disease, management typically involves symptom control using medications such as alpha-blockers, beta-blockers, and inhibitors of catecholamine synthesis to avoid serious complications. When surgery is not viable, treatment options include systemic chemotherapy with Cyclophosphamide, Vincristine, and Dacarbazine (CVD), as well as radiolabeled MIBG therapy ( AZEDRA, which was approved in 2018 but discontinued in early 2024). However, the effectiveness of CVD in improving overall survival is unclear, as most patients eventually face disease progression and death. Learn more about the PCPG treatment @ New Treatment for Pheochromocytomas and Paragangliomas DEMSER (metyrosine) was authorized for use in the United States in 1979 to treat pheochromocytoma. This FDA-approved drug is indicated for preoperative preparation, treatment of patients who are not candidates for surgery, and long-term management of malignant pheochromocytoma. In January 2019, ONO gained approval in Japan to produce and sell DEMSER capsules aimed at controlling catecholamine excess in pheochromocytoma patients. Later, in July 2020, the US FDA approved the first generic version of DEMSER oral capsules, manufactured by Amneal Pharmaceuticals, marking the initial generic approval for DEMSER in the US. In May 2025, Merck announced that the FDA approved WELIREG, the company's oral inhibitor of hypoxia-inducible factor-2 alpha (HIF-2α), for treating adults and children aged 12 and older with locally advanced, inoperable, or metastatic pheochromocytoma or paraganglioma (PPGL). The approval was based on findings from the LITESPARK-015 clinical trial, a single-arm study in which the primary measure of efficacy was the objective response rate (ORR). The trial included 72 patients in a single group (Cohort A1) with measurable disease confirmed by blinded independent central review (BICR) per RECIST v1.1. All participants had a histopathological diagnosis of PPGL and either locally advanced or metastatic disease not suitable for surgical or curative treatment. Their blood pressure was adequately controlled (below 150/90 mm Hg for adults and below 135/85 mm Hg for adolescents) without recent changes in antihypertensive therapy. Patients with carcinomatous meningitis were excluded. Participants received WELIREG at 120 mg once daily until disease progression or the onset of unacceptable toxicity. The primary efficacy endpoint was ORR as assessed by BICR under RECIST v1.1 criteria. Secondary endpoints included duration of response and time to initial response. WELIREG's prescribing information includes a boxed warning noting that exposure during pregnancy may cause harm to the fetus. Healthcare providers are advised to confirm pregnancy status before starting treatment and to counsel patients on the importance of using effective non-hormonal contraception, as WELIREG can reduce the effectiveness of hormonal methods. Additionally, the drug may lead to severe anemia requiring blood transfusions and serious hypoxia, which could necessitate treatment discontinuation, supplemental oxygen, or hospitalization. Regular monitoring for anemia is recommended before and during therapy. Find out more on FDA-approved PCPG drugs @ Pheochromocytomas and Paragangliomas Treatment Options Ongoing clinical trials are assessing a range of targeted therapies aimed at improving treatment outcomes for PCPG. These include radionuclide therapies using SSTR2 agonists and antagonists, alpha-emitting agents, and SSTR2 analogs. Other approaches under investigation involve Dopamine Receptor D2 (DRD2) modulators and ClpP agonists. Each therapy employs distinct mechanisms of action, offering promising advantages and making them key candidates in the advancing PCPG therapeutic landscape. Radionuclide therapy works by delivering radiolabeled peptides to tumor cells via specific receptor targeting. Current clinical guidelines suggest that radioligand therapy may serve as a suitable first-line treatment for patients with slowly to moderately progressive metastatic PCPG, provided the tumor demonstrates uptake of the relevant radioisotope. Several prominent institutions, including the National Cancer Institute (NCI), M.D. Anderson Cancer Center, Gustave Roussy Cancer Campus, and Columbia University are actively conducting clinical studies in this area. Discover which therapies are expected to grab major PCPG market share @ Pheochromocytomas and Paragangliomas Market Report Some of the drugs in the pipeline include ONC201 (Jazz Pharmaceuticals/Chimerix), [212Pb]VMT-α-NET (Perspective Therapeutics), and LUTATHERA (Lutetium [177Lu] oxodotreotide/dotatate) (Novartis), among others. ONC201, also known as dordaviprone, is a first-in-class small-molecule imipridone that specifically targets the G-protein-coupled receptor DRD2 and the mitochondrial protease ClpP. It was investigated in a Phase II, open-label, investigator-initiated trial at the Cleveland Clinic, involving 30 patients with rare neuroendocrine tumors. Interim results demonstrated a 50% overall response rate (ORR) in paraganglioma cases with dopamine-secreting tumors located outside the brain. These findings, based on investigator assessments, were presented at the 2021 ASCO Annual Meeting and later published in Clinical Cancer Research in 2022. [212Pb] VMT-α-NET is a Targeted Alpha Therapy (TAT) radiopharmaceutical in clinical development for diagnosing and treating SSTR2-positive neuroendocrine tumors, a challenging and uncommon cancer type. Perspective Therapeutics is conducting a multicenter, open-label Phase I/IIa dose-escalation and expansion trial (NCT05636618) in patients with unresectable or metastatic SSTR2-expressing tumors who have not previously received peptide receptor radionuclide therapy. The FDA has granted Fast Track Designation (FTD) for this program based on encouraging preclinical data, regardless of patients' prior treatment history. As of February 2025, 30 patients have been enrolled in Cohort 2, with regulatory alignment pending for Cohort 3. In April 2025, Perspective Therapeutics announced that data from both the [212Pb] VMT-α-NET and [212Pb] VMT01 programs had been accepted for presentation at the upcoming ASCO Annual Meeting, scheduled for May 30–June 3, 2025, in Chicago, Illinois. Details for regular abstracts are expected to be released on May 22, 2025, at 5:00 PM EDT. Discover more about drugs for PCPG in development @ Pheochromocytomas and Paragangliomas Clinical Trials The anticipated launch of these emerging therapies for PCPG are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the PCPG market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for PCPG is expected to grow from USD 310 million in the 7MM in 2024 at a significant CAGR by 2034. Increasing awareness and improved detection rates are contributing to a rising patient pool. Additionally, ongoing research and development of novel treatment options, including precision medicine approaches, are fueling market expansion. The growing prevalence of these rare neuroendocrine tumors, coupled with supportive healthcare infrastructure, further boosts market opportunities worldwide. DelveInsight's latest published market report, titled as Pheochromocytomas and Paragangliomas Market Insight, Epidemiology, and Market Forecast – 2034 , will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the PCPG country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The PCPG market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Incident Cases of PCPG Occurrence or Absence of mutation in PCPG Age-specific Cases of PCPG Stage-specific Cases of PCPG The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM PCPG market. Highlights include: 10-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this PCPG market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the PCPG market. Also, stay abreast of the mitigating factors to improve your market position in the PCPG therapeutic space. 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