Boston Scientific is preparing a major sales and marketing effort to support an expanded indication for its cardiac resynchronization therapy devices based on the results of the MADIT-CRT trial.

Data from MADIT-CRT released Sept. 1 show that cardiac resynchronization devices with a defibrillation function (CRT-D devices) are significantly more effective than implantable cardioverter defibrillators (ICDs) alone for decreasing the risk of heart failure events in patients with early stage, relatively asymptomatic disease. (See sidebar: " ¹ Trial Shows Resynch Therapy Slows Early Heart Failure ".)

"MADIT-CRT is the first trial to demonstrate that device therapy slows the progression of heart disease in mild to moderate heart failure patients," Boston Scientific Cardiac Rhythm Management President Fred Colen said during a Sept. 1 conference call. "We as a company are well positioned to be able to take advantage of this once we get an indication expansion from the FDA."

The company stressed that it cannot promote its CRT-D devices for the MADIT-CRT indication until FDA approves the label expansion. However, because the results have already been published in the New England Journal of Medicine, "there's a lot we can do from a medical education standpoint," explained Chas McKhann, Boston Scientific VP for Cardiac Rhythm Management Marketing.

"This is a big piece of news to be able to energize the implanting physicians to be able to go back and talk to their referral chain," McKhann said. "Our sales force woke up to all kinds of training materials this morning at about 5 a.m. and they'll be ready ... to really make the most out of these data, both for implanting physicians, as well as referring physicians." The company is also preparing materials on MADIT-CRT for its medical education programs, fellows education programs and online channels, he said.

Boston Scientific's CRT-D offerings include the Cognis CRT-D, which the company touts as the smallest, thinnest CRT-D in the world, the Contak Renewal 3 RF and the Livian .

Boston Scientific expects to submit the MADIT-CRT data to FDA for the expanded indication by the end of 2009 and expects the agency to approve it by mid-2010, Colen said. Expanding the indication to early-stage heart failure patients will create "additional opportunities for the market as a whole and for Boston Scientific specifically."

To date, FDA approval for CRT therapy has been limited to patients with New York Heart Association Class III or Class IV heart failure. The current CRT-D indication was established by the 2004 COMPANION trial, which was sponsored by Guidant before it was acquired by Boston Scientific in 2006 (² Also see "Guidant CRT-D Non-Ischemic Label Expansion Endorsed By FDA Panel" - Medtech Insight, 2 August, 2004.).

The company is now planning to submit the MADIT-CRT data to FDA to support expanding the indication for its CRT devices to patients with NYHA Class I and II heart failure. About 70% of heart failure patients worldwide, or about 22 million individuals, are in Class I or Class II, according to Boston Scientific.

NYHA Class I heart failure includes patients with no limitation of activities or symptoms from ordinary activities, while Class II includes patients with mild limitations in activity who are comfortable during rest or mild exertion.

CRT-D Makes Patients Feel Better

MADIT-CRT investigator David Wilber, M.D., Loyola University, Chicago, told "The Gray Sheet" that he expects that patients and doctors will find the MADIT-CRT data persuasive, even though the trial has so far not shown that CRT-D improves mortality.

"These are people who are functional Class I and II, so you'd expect them to have an extremely low mortality - one or two percent," he said. "So we don't expect to see mortality differences from this for several years."

"In order to see a big mortality difference, you'd have to start with a much sicker population, and that's what the previous CRT trials, such as COMPANION, were all about ... But what was surprising was the magnitude of the reduction in heart failure admissions," Wilber said, noting that the trial was designed to show at least a 20% difference in the primary endpoint of death plus heart failure events, but in fact showed more than a 30% difference.

Wilber believes it will be easier to convince patients and doctors to adopt CRT-D for early-stage heart failure than it has been to sell ICDs to prevent sudden cardiac death in heart failure patients - the so-called MADIT-II indication. "It's actually less problematic because patients readily accept the idea of taking something that's going to help them feel good and prevent them from feeling worse," he said.

"It is the symptomatic improvement from these [CRT-D] devices - in other words, quality of life - that makes a more compelling argument for patients to buy into this," he said. "If I were a patient with bad ventricular function and generally felt pretty good, and if I understood that my future held getting shorter breath and doing less and less exercise and ultimately being hospitalized for fluid overload, it would make far more impact for me to get this treatment than the theoretical risk that I could die someday suddenly but this device would prevent it."

"We've found that the symptom argument actually has a bigger impact on patients than [lowering the risk of sudden death]," he said. "So I suspect that this aspect of therapy will be relatively widely accepted by patients."

Boston Scientific has not yet released the quality-of-life data collected from MADIT-CRT, but Wilber said it is reasonable to expect the quality-of-life scores from the CRT-D group to be significantly better than those from the ICD-only group. "We expect that it will have impact on quality of life because if heart failure admissions are reduced, then it's likely that these patients simply had fewer symptoms most of the time and you'd expect that to translate into quality of life."

During the conference call, lead MADIT-CRT investigator Arthur Moss, M.D., University of Rochester, affirmed that the quality-of-life data collected in the trial will show a significant advantage for CRT-D over ICD-alone.

"We have the preliminary data. There is significant improvement in the quality of life in the CRT-D versus the ICD, and that quality of life progressively improves," he said. "There's some improvement by one year, but as we follow the patients out longer, the result is more striking and it is significant."

Analysts Foresee More CRT-D In ICD Sales Mix

Competing CRT device makers have indicated that they also will seek approval for expanded labeling to include early-stage heart failure patients (³ Also see "MADIT-CRT Data Support Expanded Cardiac Resynchronization Market" - Medtech Insight, 29 June, 2009.). Medtronic's CRT-D devices include Concerto and InSync. St. Jude offers Atlas+ HF , Atlas II HF , Epic HF , Epic II HF and Promote RF . Biotronik markets the Lumax 540 HF-T , Lumax 300 / 340 HF-T and Stratos LV .

Several securities analysts expect the MADIT-CRT results will have a significant impact on these companies' revenues by increasing the ratio of CRT-D devices to ICD-only devices. A CRT-D device costs about $7,500 more on average than an ICD, according to Boston Scientific.

The MADIT-CRT data is "without question, a catalytic event," J.P Morgan analyst Michael Weinstein said Sept. 1. "We think the industry has its best opportunity in years to re-engage the referring physician, spark a new dialogue on heart failure, and drive reacceleration in market growth."

Morgan Stanley's David Lewis writes that CRT-Ds currently represent about 35% of all defibrillator devices (ICDs plus CRT-Ds) sold worldwide, but that the MADIT-CRT findings could push the CRT-D portion of the mix up to 43% by 2012 and could accelerate the annual growth of overall defibrillator revenues from about 5% to around 6.4%. He also expects the overall demand for ICDs and CRT-Ds to grow, bringing the worldwide market for defibrillators to about $8.7 billion by 2012.

St. Jude stands to reap the most benefit from the shift, Lewis says, because it is "most leveraged to defibrillators." He expects the projected growth in this segment will accelerate St. Jude's earnings per share growth by 3.5% by 2012, while helping Medtronic and Boston Scientific's EPS by about 2% by 2012.

Wells Fargo analyst Larry Biegelsen said Sept. 1 that he surveyed 66 U.S. electrophysiologists in June to estimate the likely impact of the MADIT-CRT results. About 68% of the respondents agreed that less than 20% of patients who meet the MADIT-CRT criteria are currently getting a CRT-D device. Survey respondents, on average, expect about 61% of patients meeting the MADIT-CRT criteria to receive a CRT-D within the next three years. The surveyed doctors expect that the MADIT-CRT data will drive up overall ICD/CRT-D referrals by about 15% over the next two years.

Biegelsen projects the total ICD/CRT-D market will grow about 4.6% in 2009 to around $6.7 billion and by about 10.4% in 2010 to $7.4 billion, with about two-thirds of that revenue coming from the United States.

This is in line with the company's expectations. Colen said the new indications could expand the overall defibrillator market, including both ICD and CRT-D devices, by as much as $250 million in the United States, and $400 million to $500 million worldwide over the next few years.

- Reed Miller ( ⁴ re.miller@elsevier.com )

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