Pipeline

OVERVIEW

Zanidatamab, or Ziihera® (zanidatamab-hrii) in the United States, is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2. Zanidatamab has been granted two Fast Track designations by the U.S. Food and Drug Administration (FDA): one as a single agent for refractory biliary tract cancers (BTC) and one in combination with standard-of-care (SOC) chemotherapy for first-line gastroesophageal adenocarcinoma (1L GEA). Zanidatamab has also received Orphan Drug designations from the FDA for the treatment of biliary tract and gastric cancers, as well as Orphan Drug designation from the European Medicines Agency for the treatment of gastric cancer and BTC.

CLINICAL TRIALS

Currently, the Phase 3 HERIZON-GEA-01 trial evaluates zanidatamab in combination with chemotherapy and with or without the checkpoint inhibitor tislelizumab as a first-line treatment for metastatic HER2-positive (HER2+) GEA. Read more about the pivotal trial (NCT05152147) here.

The Phase 3 HERIZON-BTC-302 trial evaluates zanidatamab and CisGem (cisplatin plus gemcitabine) with or without the addition of a programmed death protein 1/ligand 1 (PD-1/L-1) inhibitor versus CisGem with or without a PD-1/L1 inhibitor in adult participants. Read more about the trial (NCT06282575) here.

The Phase 3 EmpowHER trial evaluates zanidatamab compared to trastuzumab, each in combination with physician's choice of chemotherapy, for the treatment of participants with metastatic HER2-positive breast cancer who have progressed on, or are intolerant to, previous T-DXd treatment. Read more about the trial (NCT06435429) here.

Additionally, Phase 2 trials are investigating zanidatamab both as a monotherapy and in combination with chemotherapy and/or other agents in BTC, GEA, breast cancer, colorectal cancer (CRC) and HER2-expressing cancers:

• The DiscovHER-Pan-206 trial evaluating zanidatamab monotherapy in previously-treated patients with HER2+ (IHC 3+) cancers including breast, gastric, esophageal, gastroesophageal, colorectal, endometrial, non-small cell lung, ovarian, urothelial, salivary and pancreatic. Learn more about this trial (NCT06695845) here.
• Zanidatamab in addition to SOC chemotherapy is being evaluated in Phase 2 trial for BTC, GEA and CRC. Read more about the trial (NCT03929666) here.
• Phase 2a study investigating the safety, tolerability and anti-tumor activity of zanidatamab in combination with fulvestrant and palbociclib in patients with locally advanced and/or metastatic HER2+/hormone receptor-positive breast cancer. Learn more about the study (NCT04224272) here.
• Phase 2 trial evaluating the safety and tolerability of zanidatamab with evorpacept (ALX148) in patients with advanced HER2-expressing cancer. Learn more about the trial (NCT05027139) here.
• Phase 2 investigation of serial studies to predict the therapeutic response with imaging and molecular analysis 2 (I-SPY 2) trial assessing the efficacy of novel drugs in sequence with standard chemotherapy to advance approaches to personalized medicine. This trial is conducted in collaboration with QuantumLeap Healthcare Collaborative. Learn more about I-SPY 2 (NCT01042379) here.
• In collaboration with the Canadian Cancer Trials Group, the efficacy of zanidatamab in combination with usual care, paclitaxel and ramucirumab, is being evaluated in Phase 2 trial in HER2+ advanced GEA. Read more about the study (NCT06043427) here.
• Phase 2b HERIZON-BTC-01 trial evaluating zanidatamab as a second-line (2L) monotherapy for treatment of HER2-amplified BTC. Learn more about the pivotal trial (NCT04466891) here.
• Phase 2 single-arm open-label pilot trial evaluating zanidatamab in patients with early-stage, low-risk, HER2-positive breast cancer. This study is being completed as part of the collaboration with the MD Anderson Cancer Center. Learn more about the study (NCT05035836) here.

Zanidatamab is also being investigated in Phase 1 studies, including the I-SPY Phase 1/1b platform trial with multiple ongoing drug regiment arms, evaluating single agents or combinations for breast cancer patients. Promising treatment regiments are to be transferred into the I-SPY 2 SMART Design Trial (NCT01042379). Learn more about Pre-I-SPY/I-SPY-P1 (NCT05868226) here.

OVERVIEW

Lurbinectedin, or Zepzelca^® in the United States and Canada, is an alkylating drug that binds guanine residues within DNA, which triggers a cascade of events that can affect the activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in disruption of the cell cycle and eventual cell death.

CLINICAL TRIALS

In addition to being approved for small cell lung cancer (SCLC), the effectiveness of lurbinectedin is being evaluated in adult patients with extensive-stage SCLC (ES-SCLC). The Phase 4 prospective, multi-center observational study aims to collect safety and outcome data of lurbinectedin in adult participants with ES-SCLC previously exposed to at least one line of chemotherapy. Learn more about the study (NCT04894591) here.

Currently, lurbinectedin is also being evaluated in combination with other agents for the following:                                       
 

• Phase 3 trial evaluating and comparing the activity and safety of lurbinectedin as a single agent and in combination with irinotecan in SCLC patients. This trial is being conducted by PharmaMar as part of Jazz’s partnership with the company. Learn more about the study (NCT05153239) here.
• Phase 3 trial evaluating lurbinectedin in combination with the PD-L1 inhibitor, atezolizumab, as a first-line maintenance treatment for patients with ES-SCLC. The trial will measure the progression-free survival and overall survival benefits of lurbinectedin and atezolizumab administered in combination compared to atezolizumab alone. The trial is conducted in collaboration with F. Hoffmann-La Roche Ltd. Learn more about the IMforte Phase 3 trial (NCT05091567) here.

OVERVIEW

JZP351, or Vyxeos^®/Vyxeos Liposomal in approved markets, is a liposomal combination of daunorubicin, an anthracycline topoisomerase inhibitor, and cytarabine, a nucleoside metabolic inhibitor.

CLINICAL TRIALS

Jazz Pharmaceuticals is collaborating with the University of Texas MD Anderson Cancer Center on one Phase 1 and two Phase 2 trials investigating JZP351 on its own and in parallel with other approved therapies, respectively, for potential indications in higher-risk myelodysplastic syndromes (MDS), relapsing/refractory acute myeloid leukemia (R/R AML) or hypomethylating agents (HMA) failure MDS.

Additional Phase 2 and Phase 3 trials of JZP351 are evaluating the agent in various age populations, and are being conducted with cooperative groups such as the AML Study Group (AMLSG) and the European Myelodysplastic Neoplasms Cooperative Group (EMSCO).

OVERVIEW

An investigational pan-RAF inhibitor for the treatment of solid tumors and hematologic malignancies that contain mutations in the mitogen-activated protein kinase (MAPK) pathway. JZP815 targets specific components of the MAPK pathway that, when activated by oncogenic mutations, can be a frequent driver of human cancer. JZP815 potentially inhibits both monomer- and dimer-driven RAF signaling (e.g., RAS-induced), prevents paradoxical pathway activation induced by BRAF selective inhabitation and is active against class 1, class 2 and class 3 BRAF mutants as well as BRAF fusions and CRAF mutants.

CLINICAL TRIALS

Learn more about the Phase 1, open-label, first-in-human study (NCT05557045) here.

OVERVIEW

Investigational JZP898, previously WTX-613, is a conditionally activated IFN⍺2b cytokine pro-drug.

CLINICAL TRIALS

The safety, tolerability, pharmacokinetics, immunogenicity and preliminary antitumor activity of JZP898 both as a monotherapy and in combination with pembrolizumab is being investigated in Phase 1, first-in-human study. Read more about the study (NCT06108050) here.

OVERVIEW

KRAS (Kirsten rat sarcoma virus) inhibitor program, including G12D selective and pan-KRAS molecules, acquired from Redx Pharma.

OVERVIEW

Evaluating patented CombiPlex^® platform in a wide range of tumor types. Evaluating improvement in cancer therapy by using extremely small (nano-scale) carriers to deliver optimal ratios of multiple anticancer agents directly to cancer cells over a prolonged period of time.

OVERVIEW

Epidiolex^® (cannabidiol), known as Epidyolex^® in the European Union (EU), United Kingdom (U.K.), Australia and Israel, is a prescription, plant-derived cannabis-based medicine administered as an oral solution. In the United States, Epidiolex is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in patients 1 year of age and older. In the EU and U.K., Epidyolex is indicated for use as adjunctive therapy of seizures associated with LGS or DS, in conjunction with clobazam, for patients 2 years of age and older. Epidyolex is also indicated for use as adjunctive therapy of seizures associated with TSC for patients 2 years of age and older.

CLINICAL TRIALS

Jazz’s GW Pharmaceuticals initiated clinical trials of Epidyolex in Japan in October 2022. The study tests the efficacy and safety of the drug in patients with LGS, DS and TSC.

OVERVIEW

JZP441, previously referred to as DSP-0187, is a potent and highly selective oral orexin-2 receptor agonist with potential applications for the treatment of narcolepsy, idiopathic hypersomnia and other sleep disorders.

CLINICAL TRIALS

The safety, tolerability, pharmacokinetics and pharmacodynamics of JZP441 are being investigated in narcolepsy Type 1 patients.

OVERVIEW

Planned. Extended-release oxybate formulation.