Positive Vote From FDA Advisors for Subcutaneous ICD

Reed Miller

April 30, 2012

April 26, 2012 (Gaithersburg, Maryland) — Cameron Health's subcutaneous implantable cardioverter defibrillator (S-ICD) seems to be on its way to becoming the first completely subcutaneous implantable defibrillator available in the US after an FDA advisory panel endorsed the company's premarket approval application at its April 26, 2012 meeting [1].

The agency's Circulatory System Devices Panel voted seven to one that the device's benefits outweighed its risks and that the company had provided reasonable assurance of its efficacy.

Panelist Dr Ralph Brindis (Oakland Kaiser Medical Center, CA) said, "The opportunity to be able to have a device to, in particular, manage patients who have infections of transvenous [ICD] systems is a very important adjunct to the armamentarium."

He predicts the S-ICD will appeal to patients who are currently choosing not to get an ICD because they fear the complications associated with transvenous leads, including lead failures or infections. "This device may offer an opportunity for this important therapy to be available to populations who are underserved."

Dr Richard Lange (University of Texas, San Antonio) referred to the S-ICD as "I-should-have-thought-of-that technology. It's really elegant and simple and a great addition to what we have available."

Dr David Milan (Massachusetts General Hospital, Boston), the only panelist who voted against recommending FDA approval of the S-ICD, said that he hopes this device "will rejuvenate enthusiasm for a field that has been plagued by repetitive reports of device recalls and malfunctions. I hope this device will get the patients who have a clear indication for a defibrillator but haven't been treated yet into our offices so we can help them."

Cameron's application was based primarily on the results of a 330-patient, 33-center trial comparing the S-ICD with objective performance criteria. All of the patients were indicated for an ICD according to class I or II professional guideline recommendations or were getting a replacement for a transvenous ICD. In the study, the S-ICD system successfully converted 100% investigator-induced VFs, beating the preset target of 88%.

Despite that high success rate, Milan said he could not vote in favor of approval at this time because he is concerned that, outside of the EP lab, the S-ICD undersenses ventricular fibrillation and sometimes waits too long to begin delivering therapy. Only 16 patients in the study experienced a spontaneous ventricular-fibrillation (VF) or ventricular-tachycardia (VT) episode. These 16 patients experienced a total of 28 "discrete" episodes and 81 recorded events that were part of longer "storms." Although the device never failed to save the patient's life, Milan suggested that a larger data set may be necessary to be certain of the device's efficacy.

The S-ICD delivered therapy within 21 seconds of the onset of arrhythmia in 95% of events. The device responded within 18 seconds in 88% of events. Milan said that if a transvenous ICD in one of his patients failed to respond to 12% of events within 18 seconds, he would consider repositioning the leads. So he was not convinced that the existing clinical data adequately demonstrate that the S-ICD's efficacy "meets what we've come to expect as the standard in the field. And the standard is quite high for transvenous systems."

Freedom from system-related complications at 180 days was 99%; the predefined success criterion was 79%. There were four system infections requiring explants and 14 incisional/superficial infections not requiring explants, comparable to standard ICDs, according to the company. The rate of inappropriate shocks was also similar to that of standard transvenous devices.

The company is proposing to conduct a postapproval registry study with at least 650 patients followed for at least three years based on the data collected in the National Cardiovascular Data Registry. The panel suggested that Cameron work with the FDA to ensure that the study addresses subgroups underrepresented in the pivotal trial, including more women and older patients. The panel also wants Cameron to clearly define the patient groups that are not appropriate for the S-ICD, including patients who need biventricular pacing and those at high risk for VT. Several panelists also suggested that the S-ICD pulse generator is too large to be implanted in smaller patients.

Anticipating that the S-ICD represents the beginning of a paradigm shift in ICD technology, Boston Scientific agreed to acquire Cameron Health in March for $300 million--half up front and half when the S-ICD earns FDA approval--plus up to $1.05 billion in milestone payments over the next six years. That deal is expected to close late this summer.