Although Edgewise Therapeutics’ hypertrophic cardiomyopathy asset missed expectations, Truist Securities called the data “excellent,” leaning on a safety profile that could eliminate the need for risk evaluation and mitigation strategies.
Edgewise Therapeutics’ investigational drug improved hemodynamic and biomarker outcomes in patients with hypertrophic cardiomyopathy, but the degree of benefit seems to have left investors underwhelmed.
The Colorado biotech dipped as much as 15% Tuesday morning on the readout, hitting $31.20 per share. The biotech’s stock recovered slightly throughout the day, ending the trading session at $33.95.
Edgewise is evaluating its drug candidate EDG-7500 in the Phase 2 CIRRUS-HCM trial, a multi-part open-label trial of patients with obstructive (oHCM) and non-obstructive (nHCM) hypertrophic cardiomyopathy. The 12-week data presented Tuesday involved 20 patients with oHCM and 33 with nHCM.
In the oHCM cohort, EDG-7500 led to improvements in hemodynamic measures in 90% of treated participants. In the same group, 74% of patients achieved either normalized levels of NT-proBNP—a biomarker indicative of the severity of heart failure—or at least a 50% reduction from baseline. EDG-7500 also resulted in a 24-point mean improvement on the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score, a tool used to assess heart failure symptoms and their impact on the patient’s life.
While analysts at Stifel said in a Tuesday note that these oHCM data look “solid,” they added that “investor attention had shifted to nHCM” after Cytokinetics’ Phase 3 ACACIA-HCM readout last month. There, EDG-7500 improved KCCQ scores by 12-13 points, according to a company presentation—a result that Stifel called “disappointing” compared with Cytokinetics’ FDA-approved Myqorzo (aficamten), which elicited a 11.4-point improvement in KCCQ clinical summary score in nHCM patients.
In this patient population, “the hope was that [Edgewise’s] ‘7500 could meaningfully improve beyond aficamten,” Stifel explained.
“EDG-7500 looks clearly active, but the numbers here are still small, it’s open-label, and also we don’t have any data on” maximal exercise performance, a registrational endpoint for HCM drugs, Stifel added. The KCCQ outcome in nHCM, the group added, “arguably doesn’t look all that different from” cardiac myosin inhibitors such as Myqorzo.
Aside from Cytokinetics, BMS also has a cardiac myosin blocker, Camzyos, approved for oHCM. The drug made more than $1 billion last year.
Truist Securities came out in defense of EDG-7500, however, calling Edgewise’s mid-stage data “excellent” and saying that the drug could become “a preferred HCM option.” In particular, the analysts wrote in a Tuesday investor note that “the KCCQ improvement for nHCM patients appeared to be increasing over time with no plateau” at the 12-week data cutoff.
Truist also noted that treatment with EDG-7500 led to no meaningful changes in left ventricular ejection fraction (LVEF) in both oHCM and nHCM cohorts, and that none of the patients saw their LVEF drop below 50%. Such a safety profile, according to the analysts, could eliminate the need for risk evaluation and mitigation strategies (REMS), which is required when using Myqorzo or Camzyos.
“We believe a REMS-less HCM drug, potentially such as EDG-7500, could greatly facilitate treatment in HCM and potentially additional future indications,” Truist noted.
