Renal denervation therapy is a new, minimally invasive procedure that will help people with hopelessly high blood pressure that just refuses to budge to medication. The procedure is promising to become a major income source for device makers. Front runners in the technology are Medtronic (MDT) and St. Jude Medical (STJ). It is approved in Europe but experimental in the US.
Treatment options are limited for patients with resistant hypertension (persistent high blood pressure), but renal denervation has emerged as a promising approach.
Treatment-resistant hypertension is generally defined as a blood pressure of greater than 140/90 mm Hg that cannot be controlled by taking three different medications. The threshold is lower for those with chronic kidney disease (130/80 mm Hg) and for diabetics (130/80-85 mm Hg).
Blood pressure control in the body lies primarily with the sympathetic nervous system. This system includes the major organs: the brain, the heart, the kidney and the blood vessels themselves. The kidney is a key player. Renal nerves communicate information from the kidney to the brain, and vice versa.
In people with hypertension, the renal nerves are hyperactive, which raises blood pressure. Quieting hyperactive renal nerves causes a reduction in the kidneys' production of hormones that raise blood pressure and may protect the heart, kidney and blood vessels from further damage.
European authorities have approved five systems: Medtronic's Symplicity, St. Jude's EnligHTN, Boston Scientific's (BSX) Vessix's V2, Covidien's (COV) One Shot, and ReCor's Paradise. Most of them use radiofrequency ablation but ReCor's system uses ultrasound.
In studies conducted so far, renal denervation has shown a fairly consistent blood pressure decline in the range of 26 to 32 mm Hg systolic and 6 to 17 mm Hg diastolic at 6 months.
Medtronic is the current front-runner.
Medtronic's Symplicity renal denervation system was launched in April 2010 and is currently available in parts of Europe, Asia, Africa, Australia and the Americas. It is only available in the US for investigational use.
Targeting US approval, Medtronic is running a total of 6 trials around the world, including studies in India and Japan, and asked the FDA's permission to launch a 7th that would study patients with less severe hypertension. Medtronic will gather all the data and submit it to the FDA for approval, possibly in 2015.
The device uses a minimally invasive procedure. The doctor inserts a steerable catheter into the renal artery, and Symplicity's radio frequency energy electrode tip performs a series of two-minute ablations to arterial nerves. Once the process is completed, the catheter is pulled out and there's no need for permanent implants.
In March, Medtronic released 24-month data from its Symplicity HTN-2, the first randomized clinical trial investigating renal denervation. Symplicity sustained an average 31-mmHg drop in systolic blood pressure during two years of follow-up. Those results all go into Medtronic's registry of the more than 5,000 patients who have been treated with Symplicity around the globe, a pool of positive data Medtronic is counting on to keep the device on top abroad.
"Symplicity has been on the market the longest and has the most robust data set," Medtronic Vice President Nina Goodheart said. "We haven't seen a huge amount of commercial activity around the other devices. What physicians are telling us is that Symplicity is still a leader in the market, and our intention is to keep it there."
The device was originally developed by Mountain View, CA-based Ardian. Medtronic bought Ardian for $800 million cash in 2010, plus commercial milestone payments through 2015.
Medtronic expects to receive a European approval for its improved second generation multi-electrode catheter this summer. This product will take ablation time down from 16 to 24 minutes today to only 2 minutes and will offer a very small 6-French size catheter that is suitable for special cases.
St. Jude Medical is right on the heels of Medtronic.
St. Jude is running three overseas studies, and it has not started its FDA-targeted trial yet, although it plans to start enrollment for it later in 2013.
In the first trial of EnligHTN, the device demonstrated an immediate systolic pressure reduction of 28 mmHg and sustained a 26-mmHg decrease through 6 months.
In the next EnligHTNment trial, St. Jude is out to prove that EnligHTN can make a meaningful difference in reducing the rates of major cardiac events.
This is important: If EnligHTNment is able to prove that renal denervation is more than just a treatment for high blood pressure but it has a positive effect in preventing heart attacks, stroke and death it could become a standard of care.
St. Jude's Cardiovascular President Frank Callaghan claims that his company has a leg up on Medtronic in both convenience and procedure time.
Currently Symplicity uses a single electrode to ablate nerves in the renal artery, moving up and down the vessel with a mean procedure time of 16 to 24 minutes. EnligHTN, on the other hand, is tipped with a basket of four evenly spaced electrodes, allowing it to ablate all the way around the artery without the risk of putting lesions in the same place. That design let's it do the same job as Symplicity in as little as 12 minutes.
"Ease of use is a big deal," Callaghan said. "It's a multi-electrode system, which makes it easier to use and probably contributes to the really strong data that we're getting from our trial."
But Medtronic is moving in the same direction with its second generation device, which will on the market this summer. The new device will use four electrodes arrayed in a spiral, a design that makes for a speedier, more predictable process.
Not to be outdone, St. Jude is working on its next-generation model too, and a new device firing all its electrodes at the same time, treating the whole artery in about 60 seconds.
The blood pressure market is enormous.
Hypertension drug sales, led by Novartis AG's Diovan, totaled $13.9 billion globally in 2011, according to IMS Health.
More than 42 million people take drugs to curb hypertension in the U.S. alone.
76 million Americans and about 120 million people worldwide, have blood pressure over 140/90 mmHg, the threshold for hypertension and a major risk factor for stroke and heart disease. It is projected that by 2025 there will be about 1.5 billion people with some form of hypertension.
Of those, an estimated 10 percent get no relief from available drugs.
Renal denervation has a bright future. Every 20-mmHg decline in blood pressure cuts the risk of major cardiovascular events in half, and continued positive results from devices like EnligHTN and Symplicity have the potential to change the way the healthcare industry thinks about hypertension.
Analysts figure the market for devices like Symplicity and EnligHTN will soar past $2.8 billion by 2020, and, by then, Medtronic and St. Jude will likely have to contend with Boston Scientific, Covidien and any other newcomer for the biggest share of that sum.
On the negative side, not all patients have a reduction in blood pressure with renal denervation and factors that predict the likelihood of a response are lacking.
On the positive side, at the moment, Symplicity and EnligHTN are indicated solely for drug-resistant hypertension, but their warm reception among European cardiologists suggests they will eventually be approved for other varieties of the ailment.
In the third quarter, which ended January 25, 2013, Medtronic has reported a total revenue of $4.0 billion, an increase of 4 percent from the previous year, on a constant currency basis.
Third quarter revenue by region were as follows: Central and Eastern Europe 24%, the Middle East and Africa grew 23%, growth in Greater China was 22%, South Asia 20%, growth in Asia Pacific was 15% including 18% growth in Japan, Latin America grew 14%.
Growth in the U.S. was 1% while Western Europe and Canada declined 1%. Emerging markets grew a combined 21% in Q3 and represented 12% of the total sales mix.
Medtronic's results were driven by solid growth in the coronary, endovascular, structural heart and AF Solutions, partially offset by declines in ICDs.
For fiscal year 2013, the company continues to expect full-year revenue growth in the range of 3 to 4 percent on a constant currency basis. Earnings per share is projected in the range of $3.66 to $3.70, which implies annual diluted EPS growth in the range of 6 to 7 percent.
In renal denervation, revenue is lagging behind the company's expectations due primarily to the lack of broad reimbursement and limited funding for new technology in nearly every European market. Many referring physicians and payers are waiting for larger datasets and longer-term follow-up.
Medtronic believes, however, that the technology, strong clinical data, and significant intellectual property represents a large multi-billion dollar opportunity in the future.