XyloCor's Phase 2 EXACT Trial Success
By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1
If you’re a regular listener of Cell & Gene: The Podcast, you may know that on Episode 10, I interviewed XyloCor Therapeutics’ CEO, Albert (Al) Gianchetti about the clinical-stage biopharma’s EXACT clinical trial. Indeed, we’ve been following XyloCor’s progress, which you can read here and here.
XyloCor is focused on the development of novel gene therapy for unmet needs in advanced coronary artery disease (CAD). During the episode, we discussed XyloCor’s EXACT clinical trial, the Phase 1/2 multicenter, open-label, single arm, dose escalation trial for CAD — the most common type of heart disease. At the time of the recording, Gianchetti talked us through the data that was available at the time and the desired outcome of the trial. Fast forward to now as XyloCor just announced the completion of the Phase 2 portion of its EXACT trial, designed to assess the safety and preliminary evidence of efficacy of lead gene therapy candidate XC001 (encoberminogene rezmadenovec) in patients with refractory angina. EXACT met both safety and efficacy objectives. There were no safety issues related to drug product or unexpected serious adverse events related to XC001 administration. Six-month data from 28 patients in the Phase 2 portion of the study showed improvements in several key efficacy measures, including reduction in ischemic burden. I caught up with Gianchetti to bring us up to speed on the latest developments and achievements. Here’s what he had to say.
Explain XC001.
XyloCor is developing XC001, a gene therapy coding for multiple isoforms of vascular endothelial growth factor (VEGF) that stimulates the creation of new blood vessels (angiogenesis) in ischemic myocardium, as a treatment for patients with refractory angina (RA). Because the vector expresses multiple isoforms of VEGF, there is a more potent angiogenic effect than previous approaches where only a single isoform of VEGF was expressed. In addition, because the vector is injected directly into the ischemic myocardium, a low dose is used. This approach is intended to maximize the therapeutic effect and minimize vector related toxicities.
Explain EXACT.
The EXACT (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) study is a first-in-human, multicenter, open-label, single-arm, sequential dose escalation study with a highest tolerated dose expansion phase to establish preliminary safety and tolerability of XC001 and to assess signals of efficacy at the highest tolerated viral dose in subjects with refractor angina. Patients with refractory angina have failed optimal medical therapy and are no longer candidates for PCI (often with a stent to open the diseased artery) or bypass surgery, so these patients have no treatment options and are left to suffer with their disease which leads to a poor quality of life and consumption of significant healthcare resources. The Phase 1 dose escalation portion was designed to assess preliminary safety and determine a dose to carry into Phase 2. The Phase 2 portion is to further assess safety and the highest tolerated dose and to assess the clinical effectiveness.
What is next for the trial?
We have reached the primary endpoint period in EXACT and will continue to follow patients before finalizing the trial later this year. In addition, we look forward to finalizing our pivotal trial design through our ongoing discussions with the FDA and other regulatory authorities.
Explain XyloCor’s second preclinical investigational product, XC002.
XC002 is a gene therapy approach to administer reprogramming genes directly to the heart to turn fibroblasts (cardiac cells damaged by heart attack) into functioning cardiac cells. This approach could slow down, halt or even reverse progression to heart failure in patients who have had a heart attack.