Jazz Pharmaceuticals (NASDAQ:JAZZ) outlined development and commercial plans for its oncology, epilepsy and sleep franchises during a discussion with Deutsche Bank analyst David Hoang, emphasizing the expansion potential of HER2-targeted therapy Ziihera and ongoing lifecycle work for EPIDIOLEX.
Ziihera Data and Development Plans
An unnamed Jazz executive said zanidatamab, marketed as Ziihera, produced a statistically significant overall-survival result for its zanidatamab-plus-chemotherapy arm versus a control arm in a second interim analysis. The company had previously reported a statistically significant overall-survival benefit for a triplet regimen that included zanidatamab, chemotherapy and the PD-1 inhibitor tislelizumab.
Jazz is continuing several Ziihera studies, including:
- A frontline biliary tract cancer trial.
- A pivotal later-line breast cancer trial.
- A pan-tumor trial intended to support a possible tumor-agnostic indication for HER2-overexpressing tumors that have not responded to standard therapies.
The company said colorectal cancer findings from its broader program, along with other data, supported an FDA breakthrough therapy designation in second-line colorectal cancer. Jazz said it is discussing a potential approval pathway in colorectal cancer with the FDA and may also pursue opportunities in non-small cell lung cancer.
In explaining its interest in zanidatamab, the executive pointed to its biparatopic HER2-antibody design, which targets two binding sites on the receptor. According to the company, the design can drive receptor clustering and internalization, activate the complement cascade and recruit immune cells. Jazz said those characteristics may help explain activity in PD-L1-negative gastric cancer patients and support the potential for combination treatment with PD-1 inhibitors.
Commercial Outlook for Gastric Cancer
Jack Spinks, Executive Director of Investor Relations at Jazz, said the company estimates an annual incidence of roughly 8,000 HER2-positive gastroesophageal adenocarcinoma patients, while its estimate of 3,000 to 4,000 treatable patients accounts for unresectable disease, first-line treatment and testing rates.
Spinks said Ziihera had launched three weeks earlier and that Jazz expects the therapy to become a first-line standard of care. The company said it believes zanidatamab should replace trastuzumab in first-line HER2-positive gastroesophageal adenocarcinoma, with most patients receiving the triplet regimen including tislelizumab.
Jazz noted that potential competing first-line studies involving trastuzumab deruxtecan were not expected to read out until 2029. The company also argued that zanidatamab’s use alongside chemotherapy offers flexibility because chemotherapy can later be reduced or discontinued while HER2-targeted treatment and PD-1 therapy continue. By contrast, the company said antibody-drug conjugates retain their chemotherapy payload.
The executive said Jazz has raised its estimate of Ziihera’s potential revenue opportunity from more than $2 billion to a range of $3 billion to $5 billion, reflecting possible expansion in breast cancer, colorectal cancer, biliary tract cancer and other settings.
Epilepsy Pipeline Expansion
Jazz said EPIDIOLEX has exclusivity extending into the late 2030s and is beginning four additional clinical trials. Those studies include a Phase 2 trial in focal-onset seizures, a potentially pivotal Phase 2/3 trial in juvenile myoclonic epilepsy, a Phase 3 trial across a broader range of developmental and epileptic encephalopathies, and an adult study in Lennox-Gastaut syndrome.
The company also submitted an application for a solid oral capsule formulation of EPIDIOLEX. Jazz said the program is intended both to support existing indications and potentially broaden the treatment’s label beyond its current approvals for seizures associated with Dravet syndrome, tuberous sclerosis complex and Lennox-Gastaut syndrome.
Jazz also highlighted the closing of its Actio transaction, which adds a program aimed at a rare epilepsy associated with a single-gene mutation. The company said it expects data related to that program to be published in the future. Separately, Jazz said it plans to advance a treatment candidate for absence epilepsy and a Kv7 opener that it views as potentially best in class.
Sleep-Wake and Other Programs
In sleep medicine, Jazz said it sees continued differentiation for Xywav because of its low-sodium profile and flexible dosing options. The company said it believes orexin-2 agonists may serve as daytime wake-promoting therapies but may not replace Xywav because they do not address disrupted nighttime sleep.
Jazz recently announced that its next-generation orexin-2 agonist cleared an investigational new drug application and is expected to enter healthy-volunteer studies this year. The company said its candidate is designed with a shorter half-life and brain penetration in an effort to limit nighttime carryover effects.
The company also reiterated that an interim overall-survival analysis from the ACTION trial of Modeyso in frontline high-grade glioma is expected next year. Jazz said a positive interim analysis could provide an earlier approval opportunity, while an unsuccessful interim analysis would allow the study to continue to completion.
About Jazz Pharmaceuticals (NASDAQ:JAZZ)
Jazz Pharmaceuticals plc (NASDAQ:JAZZ) is a global biopharmaceutical company focused on developing and commercializing medicines for disorders in neuroscience and oncology. The company concentrates on conditions with significant unmet medical needs, including sleep disorders, epilepsy, rare diseases and certain cancers.
Its neuroscience portfolio includes Xywav and Xyrem, oxybate-based treatments for narcolepsy, with Xywav also indicated for idiopathic hypersomnia in adults. Jazz also markets Epidiolex in the United States, known as Epidyolex in some international markets, a cannabidiol-based medicine for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome and tuberous sclerosis complex.
In oncology, Jazz’s products include Rylaze, an asparaginase therapy used as part of treatment for acute lymphoblastic leukemia and lymphoblastic lymphoma; Zepzelca, used for certain patients with metastatic small cell lung cancer; and Vyxeos, a chemotherapy formulation for certain cases of newly diagnosed therapy-related acute myeloid leukemia or AML with myelodysplasia-related changes.
