Jazz Pharmaceuticals (NASDAQ:JAZZ) highlighted the commercial and clinical importance of zanidatamab, its HER2-targeted bispecific antibody, during a conference discussion featuring Rob Iannone, the company’s executive vice president, global head of research and development and chief medical officer.
Iannone described zanidatamab as a “bispecific biparotopic antibody” designed to bind two different HER2 receptor epitopes, corresponding to the binding domains of Herceptin and Perjeta. He said the structure causes HER2 receptor clustering and activates immune mechanisms, including complement fixation, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.
HERIZON-GEA-01 Data Draw Physician Interest
The discussion focused heavily on HERIZON-GEA-01, Jazz’s frontline gastroesophageal adenocarcinoma study. Iannone said the company has received a “very, very positive” response from physicians following the presentation of data at ASCO GI, where he said oncologists saw survival of more than two years in both zanidatamab-containing arms.
He said arm B, zanidatamab plus chemotherapy, showed more than two years of survival, while arm C, the triplet of zanidatamab, chemotherapy and tislelizumab, showed more than 26 months. Iannone characterized the results as “unprecedented” in absolute terms and compared with the control arm.
Iannone said the company sees particular significance in activity among PD-L1-negative patients. He said Jazz had expected this possibility because its thesis was that zanidatamab may trigger immune activity that could synergize with PD-1 or PD-L1 inhibitors.
“Once this is on the market, docs don’t even need to test for PD-L1, which is certainly an advantage,” Iannone said, adding that the company believes patients in the frontline gastric cancer setting should receive effective therapies early because many do not make it to second-line treatment.
Iannone said the first overall survival analysis was one of three planned OS analyses. The next analysis will focus on zanidatamab plus chemotherapy versus the control arm, with timing expected around midyear. He said overall survival was not required for approval in the company’s regulatory discussions, and that a large progression-free survival benefit with a supportive OS trend can be sufficient in the frontline setting.
Regulatory Timeline and Launch Preparation
A company representative said Jazz has received a Prescription Drug User Fee Act date of Aug. 25 for the gastric cancer application, along with Real-Time Oncology Review and priority review from the U.S. Food and Drug Administration.
The representative said the company expects the triplet overall survival data to be included in the label if approved and noted that Jazz already has approval for zanidatamab in second-line HER2-positive biliary tract cancer. The representative said there is more than 90% overlap among treating physicians between that indication and gastric cancer, which could support launch readiness.
Iannone added that Jazz is not promoting ahead of approval but has a medical science liaison team educating physicians around the data. He also said a manuscript has been accepted in a major journal and that Jazz hopes to use the publication to support efforts to obtain NCCN guideline inclusion.
Expansion Plans Beyond Gastric Cancer
Iannone said breast cancer remains an important area for zanidatamab, including the company’s 303 trial in a later-line population after antibody-drug conjugate treatment. He acknowledged that later-line breast cancer is more challenging than frontline disease but said HER2-positive breast cancer often remains HER2-driven after progression.
He said the trial is based on the idea that patients may benefit from a more effective HER2 antibody in combination with chemotherapy, particularly in a setting where patients otherwise have limited evidence-based options after prior HER2-directed therapies.
Iannone also pointed to potential future work in the neoadjuvant breast cancer setting, where he said zanidatamab may provide flexibility in combination strategies and potentially reduce toxicity in a curative setting. Jazz is also evaluating combinations with novel HER2 tyrosine kinase inhibitors through partnerships with Boehringer and Iambic, he said.
Beyond breast cancer, Iannone highlighted opportunities in first-line biliary tract cancer, neoadjuvant and adjuvant gastric cancer, colorectal cancer and non-small cell lung cancer. He said Jazz’s pan-tumor trial will enroll colorectal and non-small cell lung cancer patients with HER2 overexpression, along with patients in other rare tumors.
Sleep, Epilepsy and Other Pipeline Updates
Jazz also discussed its sleep franchise, including the potential impact of orexin therapies. Iannone said orexins represent a new class of alerting agents and said he expects data in narcolepsy type 1 could lead to approval. However, he said the root cause of hypersomnias remains severely disrupted nighttime sleep.
Iannone said Xywav, which he described as the only low-sodium option with dosing flexibility, should remain a backbone treatment for a substantial portion of hypersomnia patients. He said Jazz is also advancing its own orexin and sees the potential for complementary use.
In epilepsy, Iannone said Jazz has become a leader through its acquisition of GW and pointed to Epidiolex as a broadly used, well-tolerated therapy that can be combined with other treatments. He said genomics is transforming epilepsy in a way similar to oncology two decades ago and referenced Jazz’s work on several new agents, including an in-licensed Kv7 inhibitor from Saniona and an in-house Kv4 inhibitor.
Iannone also briefly discussed “Modesto,” saying the ACTION trial could have an interim overall survival readout by the end of the year or early next year. He said the current approval is in second line, but the ACTION trial could support a frontline label immediately after radiation therapy.
About Jazz Pharmaceuticals (NASDAQ:JAZZ)
Jazz Pharmaceuticals plc is a global biopharmaceutical company focused on developing and commercializing therapies in neuroscience and oncology. The company’s research and development efforts target unmet medical needs in sleep disorders, hematologic malignancies, rare neurological conditions and solid tumors. Jazz’s product portfolio includes therapies for narcolepsy, hepatic veno-occlusive disease, acute myeloid leukemia and other serious disorders.
Flagship products from Jazz Pharmaceuticals include Xyrem® (sodium oxybate) and Xywav® (calcium, magnesium, potassium, and sodium oxybates) for the treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy.
