BB&T Contributing Writer

BOSTON — A diverse and interesting group of private companies medical device companies were featured at this year's conference, which was held several weeks ago.

Most industry pundits would readily agree that the trans-aortic valve implantation (TAVI) space, pioneered by two of the medical device industry titans Medtronic (Minneapolis) and Edwards Lifesciences (Irvine, California) is a hugely exciting market, with enormous potential. According to various market sources, European sales for the two companies are estimated to reach about $600 million in 2011, compared to $425 million in 2010 (See Table below).

Two privately-owned, venture capital-backed companies in the TAVI area presented at the conference. Symetis (Lausanne, Switzerland) CEO Jacques Essinger stated that he expects his company to be the next entrant into the European TAVI market, which he forecasted at approximately $2 billion worldwide in 2014.

Noting that his company “wants to be ahead of the technology curve,“ Essinger praised the progress and success of both Edwards and Medtronic but also felt that their first generation technology was not easy to use, resulting in valve positioning to be heavily physician dependent.

On the contrary, the Symetis Acurate valve, in Essinger's view, is a second-generation device, which is “intuitive, recapturable and self-positioning by design.“ He reported that one implanting surgeon found the device so simple to use that he quipped maybe this device should be called “TAVI for Dummies.“

Symetis completed enrolment in its first in man (FIM) trial last September, using a trans-apical approach, with 40 patients treated in five centers in Germany. It has reported very solid six-month efficacy results, as measured by the typical measures of efficacy. The safety profile, again based on traditional measures, is solid as well.

Symetis is completing the enrolment of a 50 patients European pilot study. The pooling of the FIM and pilot data supports the filing of the CE-mark dossier.

The company hopes to have a total of 200 patients enrolled in its trans-apical studies by the end of 2011 and a CE Mark approval for that indication before year-end 2011. FIM for its trans femoral device is also expected to occur prior to the end of 2011, with a possible CE mark by late 2012 or early 2013.

Symetis has raised a total of $60 million to date from a variety of European VCs, giving it enough cash to operate through the end of 2012. Essinger indicated that it would need an additional $30 million to commercialize its device.

“We are already evaluating our strategic and financial options,“ said Essinger, “we may raise more money from our existing investors, go public or sell to a strategic buyer.“

Direct Flow Medical (Santa Rosa, California) is also a well-funded private TAVI player, having raised $75 million in three VC rounds since its founding in May 2004. CEO Bernie Lyons also praised the tremendous success of Edwards and Medtronic, citing two recent articles in the prestigious New England Journal of Medicine (September 22, 2010 and June 9, 2011) that have clearly established TAVI as an effective therapy for patients with severe aortic stenosis. He also applauded the two TAVI pioneers for their clinical excellence, commenting that the Edwards PARTNER trial was “elegant.“

However, Lyons pointed out that there are a host of side effects (strokes, major vascular complications, aortic insufficiency) that are seen with the current designs and suggested that the next generation of devices “must address these limitations.“

Key design upgrades would include a lower profile, allowing for better access and trackability and the ability to precisely position, reposition or even retrieve the valve. Benefits of a better design should include a reduction in paravalvular leakages, which in turn could result in improved patient outcomes, as measured by improved survival and a lower NYHA classification.

Lyons noted that the Direct Flow device has a “surgical valve“ design with unique features, including a conformable cuff and a precise positioning system. Its unique features allows for an assessment of patient outcomes prior to its final device deployment. He also noted that its “formed in-situ“ platform technology places its outside the “contentious“ Andersen patents, which will likely result in major patent battles for several other players.

The company's European feasibility trial, employing a 22 Fr. design, was conducted in Germany and enrolled 31 high-risk patients. Lyons described the two-year clinical results as “compelling,“ with excellent scores in all major measures of efficacy and safety.

The company has completed the development of its 18 Fr. second generation TAVI system, which will offer increased radial force, improved valve loading and positioning, simplified valve retrieval and ultimately better safety. The first cases were recently performed in Germany. The device was permanently implanted in one patient and at 6 months there was trace paravalvular V leak. In the second case a “technical problem“ with the device was discovered which lead to a serious adverse event. Following some design modifications, this trial will likely be restarted shortly.

Lyons expects that Direct Flow will attain a CE mark in the second half of 2012 and begin its U.S. IDE trial sometime in 2012.

PowerVision (Belmont, California), another VC-backed private company, is developing a proprietary accommodating intraocular lens (A-IOL) that CEO Barry Cheskin described as “a dramatic improvement over current technology.“ Its approach is fundamentally different than other A-IOLs, as it utilizes the natural muscular accommodating forces in the eye to move fluids in the IOL. This results in shape change of the IOL, tradenamed FluidVision, which is exactly what occurs in a healthy natural lens and thus provides a significant benefit in reading.

Relative to the competitive A-IOLs that are in development and the multi-focal IOLs currently on the market, Cheskin said that “we expect to be the best in class,“ with a goal to provide an average of more than 5 diopters of accommodation to the patient.

The ability to achieve a shape change in this IOL will “restore the accommodative range equivalent to a 35 year old,“ said Cheskin, a veteran CEO, who has had several successes in the med-tech industry prior to co-founding the company with Matt Frinzi, a longtime ophthalmic industry executive.

Cheskin said that the initial clinical progress has been “tremendous,“ with early human data showing that the lens indeed does change shape and provides significant accommodation. PowerVision hopes to start a trial aimed at CE mark approval in the next 12 months and begin its U.S. feasibility trial in 2013.

PowerVision has raised a total of $53 million from the venture community to date, including a Series C round of $25 million that was finalized early this year.

Another VC-backed company that is showing outstanding progress is CardioFocus (Marlborough, Massachusetts). The company, whose technology primarily addressing paroxysmal (intermittent) atrial fibrillation (AF), uses a visually guided laser balloon, a 12 Fr. deflectable sheath, a compliant and adjustable balloon that can be maneuvered easily into the pulmonary veins, ablative laser energy and direct endoscopic visualization. The direct visualization has led to a company slogan “see what you ablate, ablate what you see.“

Electrophysiology industry veteran and CEO Steve Sagon said that based upon first 325 patients treated, his company is achieving “best in class clinical results.“

“Patients and physicians deserve a high rate of success in a single procedure,“ said Sagon “and we are showing that we can indeed deliver that.“

Data from the recent Heart Rhythm Society (HRS; Washington) meeting in San Francisco showed that after a six-month follow-up for over half the 200 patients enrolled in its current study, the single procedure, drug-free rate of freedom from AF was 65%. This compares favorably to the single procedure success rate of 57% from a meta analysis of numerous randomized clinical trials and the less than 50% success rate reported in the PMA trials by both the Biosense Webster's (Diamond Bar, California) Thermocool RF catheter and the Medtronic (Minneapolis) Arctic Front cryoablation catheter.

Sagon noted that European commercialization, under the tradename Heartlight EAS, is now underway, with “high average selling prices.“ In a recent press release, Sagon said “clinical results . . . have been very promising and we are encouraged by the adoption of the technology by numerous European cardiology thought leaders. We expect to broaden the use of the system in Europe as a new treatment option for atrial fibrillation patients.“

The awareness of AF is clearing increasing in Europe. The AF AWARE partnership, a collaboration of the World Heart Federation (Geneva, Switzerland), the Atrial Fibrillation Association (Bristol, UK), the Stroke Alliance For Europe (London), and European Heart Rhythm Association (Sophia Antipolis, France) have come together to call upon their peers around the world to raise awareness and understanding of AF and its cardiovascular consequences.

The organization's November 2010 report stated that the lives of thousands of AF patients could be at risk due to poor diagnosis, failure to follow treatment guidelines and lack of quality information.

The report highlighted that AF may cost the European Union about €10 billion annually with indirect (lost work, poor productivity) patient costs of about €3,000 per year.

Worldwide TAVI Sales Projections.pdf

The group is calling for immediate action in four areas, which are shown in Table 2 below, left.

In the U.S., CardioFocus completed its feasibility trial in October 2010, treating a total of 86 patients. Following minor product improvements, the company hopes to begin its U.S. pivotal trial later this summer. A total of 300 patients will likely be enrolled, randomized 1:1 to the ThermoCool catheter (See Table 3).

Privately-owned Arstasis (Redwood City, California), which has taken a totally new approach to vascular access, is now in the midst of a nationwide rollout of its Axera (“a new era of access“) device.

Table 2

AF AWARE Recommended Initiatives

• Wider availability and use of disease registries to get a more accurate estimate of AF prevalence and assess the true burden of the disease

• More educational tools on interpreting and applying treatment guidelines to country specific needs

• An assessment of clinician training needs, patient information gaps and treatment preferences

• Quality patient materials, enabling patients to become true partners in making treatment decisions, with appropriate support from their clinicians

Source: AF AWARE report, November 23, 2010

Table 3

Cardiofocus Clinical Experience to Date

– 336 clinical cases conducted by 39 physicians at 20 institutions in Europe and U.S.

– Physicians satisfied and enthusiastic

– Common Themes:

• Short learning curve to remarkable acute success rates

• Durable chronic results demonstrated on follow-up

• No need for complex adjunctive technologies

• One catheter per patient; no touch-up

• Reduced radiation & procedure time

• No repeat procedures

Table 4

The Axera Device

1. Leaves no foreign material behind

2. Average hemostasis time of 3-4 minutes vs. 20*

3. Gets patients out of bed in 1 hour, vs, 2-8 hrs.*

4. Essentially no late bleeding

5. Is very easy to use, takes approximately one minute to deploy

6. Is compatible with any body type

7. Is compatible with and normal location of stick

8. Appears to allow immediate and long-term re-access

9. Causes less pain than any clip, suture, plug or staple

10. Similar price point to closure devices expected

* Diagnostic (angiographic) procedures

CFO Alex Arrow, MD, said that Arstasis, by changing the way that vascular entry is performed, is providing a superior way to close the access site itself. Its unique vascular access procedure results in a quick cessation of bleeding, much faster patient ambulation compared to either manual compression (70% of the market) or vascular closure devices (VCDs, which account for 30% of the market) and achieves this result without leaving any foreign substance or device in the body. (See Table 4).

Clinical data has been outstanding, with nearly 1,200 patients treated outside the U.S. demonstrating remarkable safety compared to manual compression or VCDs.

With several 510(k) clearances, Arstasis is now selling in the U.S., with 13 direct territories and a total of 52 persons serving those territories. Initial sales progress has been impressive, with 47 customers and a $3.6 million revenue run rate achieved in June.

“We hope to be at a $40-50 million run rate in 2012,“ said Arrow, who also indicated that the company recently completed a $25.5 million fund raising.

Arrow concluded his remarks saying that “we have a disruptive technology and we believe that Axera could become the new standard of care.“