Jazz Pharmaceuticals plc’s mid-stage asset suvecaltamide (JZP385) failed to show a statistically significant benefit in a Phase IIb trial in patients with essential tremor, but a second Phase II study in patients with Parkinson’s disease tremor is continuing.
Key Takeaways
- The Phase IIb failure of suvecaltamide in essential tremor could put more pressure on Jazz’s oncology pipeline to deliver.
- The company attributed the failure to a higher-than-expected placebo response in the non-treatment arm, though Jazz had changed the dosing and formulation of the drug from an earlier Phase II study.
- Suvecaltamide is also being studied in a Phase II study in Parkinson’s tremor, but the study is relying on a similar primary endpoint.
Jazz gained suvecaltamide, a first-in-class selective and state-dependent modulator of T-type calcium channels, with the $312.5m acquisition of Cavion LLC in 2019. (Also see "Jazz Pharma Zeros In On Essential Tremor With Cavion Buy" - Scrip, 13 August, 2019.) The acquisition was part of the company’s expansion in neurological conditions, where it has a heritage in sleep disorders and markets Epidiolex (cannabidiol) for seizures in certain epilepsies.
More recently, the company has been ramping up its presence in oncology, where it sells Rylaze (asparaginase Erwinia chrysanthemi [recombinant]-rywn), used as part of a chemotherapeutic regimen in acute lymphoblastic leukemia and lymphoblastic lymphoma, and Zepzelca (lurbinectedin), an alkylating drug for metastatic small-cell lung cancer. A third product, the HER2-directed bispecific antibody zanidatamab, is under US Food and Drug Administration review for second-line biliary tract cancer and is in Phase III for gastroesophageal adenocarcinoma (GEA). (Also see "Jazz Hits High Note With Updated Zanidatamab Data In Biliary Tract Cancer At ASCO" - Scrip, 4 June, 2023.)
Jazz CEO Bruce Cozadd insisted during the company’s first quarter sales and earnings call on 1 May that Jazz is not looking to be an oncology company, however, but rather to be strong in oncology and neuroscience.
But the company reported 20 June that the first of its two trials testing suvecaltamide has had a disappointing result.
Treatment with 30mg of suvecaltamide did not achieve a statistically significant benefit on the primary endpoint, change from baseline to week 12 on the Essential Tremor Rating Assessment Scale (TETRAS) modified composite outcome score in adults with essential tremor. The trial did not meet a key second endpoint either, Clinical Global Impression-Severity (CGI-S) scale. Numerical improvements were observed on the primary endpoint and secondary endpoint, however.
High Placebo Response
The company attributed the failure to a higher-than-expected improvement in the placebo arm of the trial from baseline to week 12. The improvement in the placebo arm exceeded what was observed in a prior Phase II trial called T-CALM that was conducted by Cavion prior to the acquisition by Jazz and tested a twice daily formulation of the drug.
Jazz changed the formulation of the drug in the ensuing period, from a twice-daily formulation to once daily and from 20mg a day to 30mg a day to increase exposure.
“We are disappointed that the trial did not meet its primary endpoint,” the company said in a statement. “We are evaluating the data to better understand the trial results and await the result of the suvecaltamide trial in Parkinson’s disease tremor to determine next steps for the program.”
The Phase II Parkinson’s disease trial is ongoing with results expected in the first quarter of 2025. The primary endpoint of that trial is based on the same rating scale, however, change from baseline to Week 17 on the TETRAS composite outcome score.
A new drug for essential tremor could represent a substantial commercial opportunity as there is a high unmet need for a new treatment, where there has been no new innovation. In the US and key European markets, there are approximately 2 million patients diagnosed with the movement disorder, while the prevalence is thought to be substantially higher, according to Jazz.
Wells Fargo analyst Mohit Bansal suggested in a same-day research note that the clinical trial failure would have a relatively minor impact on long-term revenue forecasts, with 2030 revenue assumptions for Jazz dropping from $4.3bn to $4.1bn.
“JZP385 is still a part of Vision 2025’s goal of greater than five novel product approvals by the end of the decade,” Bansal said, referring to the company’s long-term business strategy. However, he noted the setback puts more pressure on other pipeline programs like zanidatamab and potential new expansion updates for Epidiolex in Japan and Zepzelca in first line extensive-stage small cell lung cancer, data for which are expected in the second half of the year or early in 2025.
The Phase IIb trial evaluated suvecaltamide dosed once-daily at three oral doses,10, 20 and 30mg versus placebo. The drug was well-tolerated and the safety profile was consistent with prior studies. The most common treatment-emergent adverse events were dizziness, headache, paresthesia, diarrhea and insomnia.
