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Cardiac Dimensions Takes on Abbott and Edwards in FMR Market

Courtesy of Cardiac Dimensions Cardiac Dimensions Takes on Abbott and Edwards in FMR Market
Mitral annulus remodeled with Carillon device.

Cardiac Dimensions said it has all the makings of a dominant competitor in the functional mitral regurgitation (FMR) market.  And the Kirkland WA-based company isn’t letting the fact that it’s the smallest of three firms competing in the FMR space hinder its path in obtaining a top spot.

On Thursday, Cardiac Dimensions announced it had reached a significant milestone, by closing on a $39 million Series B round in an effort to build clinical evidence for its Carillon Mitral Contour System. The funding will be used to help continue the 450-patient CARILLON Trial Pivotal Study and complete the follow-up and publication of the landmark randomized, double-blinded REDUCE FMR global study. The U.S. trial will help the company obtain a PMA for the Carillon Mitral Contour System. The firm  has CE mark for the device. 

Cardiac Dimensions said the trials were unique because none of its competitors have a double-blinded study assessing FMR treatment.

“We have created and designed a technology that helps with an annuloplasty approach to give assistant to patients with functional mitral regurgitation,” Gregory Casciaro, president and CEO of Cardiac Dimensions. “We do it differently than some of the competition out there in that ours is called an indirect annuloplasty- meaning that we effectively try to treat those patients on their annulus but never directly.”

The company said the Carillon Mitral Contour System is introduced through a large vein from the right side of the patient.

“A very simplistic way of looking at the device is that we fix the door frame being too big for the doors,” Rick Wypych, CFO of Cardiac Dimensions, told MD+DI. “The door frame is just too big for the doors in which case the doors don’t shut appropriately. In relation to the heart, what that does is cause regurgitation, which means the blood is going the wrong way.”

The Carillon Mitral Contour System cinches the valve or doorframe smaller, so it can close appropriately. 

Against the Giants

Cardiac Dimensions might prove to be the little private company that could in the FMR market. It faces off against two publicly-traded medtech powerhouses – Abbott Laboratories and Edwards Lifesciences.

Casciaro cited Abbott’s MitraClip as the top player in the space. The technology is a surgical approach using a catheter to clip the doors or leaflets of the heart together. The MitraClip received FDA approval for the treatment of primary functional regurgitation in 2013.

The Abbott Park, IL-based company is also seeking to gain FDA approval for an FMR indication. The company completed its clinical trial for this indication and it is speculated the firm could present data at the upcoming Transcatheter Cardiovascular Therapeutics meeting.

“From there Abbott will probably go in front of the FDA and go in front of a panel,” Casciaro said.

Irvine, CA-based Edwards competes in the FMR market with the Cardioband device. Edwards gained access to Cardioband through its $340 million plus milestone payments acquisition of Valtech Cardio Ltd. Cardioband has had CE mark since 2015.

“They are a direct annuloplasty fix,” Casciaro said. “This means they go right onto the door jam and with a semicircular band they go through a transseptal puncture through the heart and screw down into their system onto the annulus directly.”

Casciaro said the recent funding round is significant because it will help the company not only become a more viable competitor, but turn the page in the company’s continuing story.

“With this funding we’re going to get the opportunity to now demonstrate to the U.S. physician base, as we’ve done over in Europe … when you’re looking for something that’s safe – we’ve got it,” Casciaro said. “When you’re looking at something that’s easy to learn and perform – we’ve got it. When you look at something that has the ability to demonstrate its performance – we’ve got it.”

Is FDA Really Streamlining Its PMA and 510(k) Processes?

TEROVESALAINEN/PIXABAY.COM Is FDA Really Streamlining Its PMA and 510(k) Processes?

In the early aughts, if a medical device manufacturer wanted to get its product to market—any market—more quickly, it often obtained a CE Mark first. At the time, the European Commission required less clinical trial data than FDA. Even for some Class III devices, clinical data would need to justify safety claims but not efficacy. Efficacy was for the market to decide.

Over the past decade, payers have gradually demanded more data, which means the CE Mark became more burdensome, time-consuming, and expensive. Last year, with the European Parliament’s approval of a final version of the Medical Device Regulations, Notified Bodies have had their hands full, to say the least.

Between now and 2020, all device manufacturers, Notified Bodies, and suppliers have to update technical documentation to comply with new standards. If a device manufacturer is not in compliance by May 2020, it risks losing CE Mark certification. For the time being, obtaining a CE Mark for timeliness reasons is not the way to go.

On this side of the pond, however, FDA has announced initiatives to purportedly streamline the premarket approval (PMA) and 510(k) process. Much of this work goes back to the 21st Century Cures Act, enacted by Congress in December 2016, which aims to bring drugs and devices to market faster. Janet Trunzo, executive vice president of technology and regulatory affairs for AdvaMed, said certain Cures Act provisions provide an expedited path for technology that meets an unmet clinical need or addresses a public health need.

In its Medical Device User Fee Amendments performance goals and procedures for fiscal years 2018 through 2022, FDA reports the average total time to decision goal for Original PMA and Panel Track Supplement submissions will decrease from 320 days in Fiscal Years 2016 through 2018 to 290 days for submissions received in FY 2020 through 2022. For 510(k) submissions, the goal decreases from 124 to 108 days.

"The user fee program is intended to bring more predictability and consistency into the review process," says Trunzo. "Getting a predictable review in timely manner is a theme built into the user fee program."

The agency is seeking comments on the draft guidance, Expansion of the Abbreviated 510(k) Program: Demonstrating Substantial Equivalence through Performance Criteria, until July 11. The guidance's intent is to streamline the "substantial equivalence" analysis required for 510(k) submission.

FDA's Software Precertification (PreCert) Pilot Program, launched last year, aims to streamline pre- and postmarket obligations for software regulated as a medical device. "Our goal is to create a program that is aligned with how products are being developed and how quickly they come to market, as well as one that's aligned internationally with other regulators," FDA associate director for digital health Bakul Patel told MD+DI in August 2017. "This is about creating a new paradigm."

The diabetes space has also realized FDA support. On September 28, 2016, FDA approved the first hybrid closed-loop system, aka an artificial pancreas—Medtronic's MiniMed 670G. In a press release, FDA said it's working with diabetes leaders to advance artificial pancreas development.

Dexcom also benefitted from an expedited FDA process. On March 27, FDA permitted marketing of its G6 integrated continuous glucose monitoring (CGM) system. At the same time, FDA classified integrated CGMs as Class II devices, which means they can receive 510(k) clearance rather than go through the more arduous PMA path.

"This greatly enhanced our time frame," said Dexcom president and CEO Kevin Sayer. "Both sides were motivated to get the rule changes in place, which accelerated our approval."

Sayer said the company knew it may receive FDA clearance ahead of schedule and planned accordingly. However, he added that it's "all hands on deck" as the company builds inventory for a launch later this quarter.

Empty Promises?

Over the past few years, FDA has promised expedited review in a few areas. If history repeats itself, Sharon Kvistad, associate director in Navigant's healthcare and life sciences disputes, regulatory, compliance, and investigations practice, said much of this talk may be just that.

"FDA is under enormous pressure from Congress to streamline and expedite," she said. "They have initiatives, programs, and expedited pathways for novel, cutting-edge devices. They want to interact early and frequently to have a voice in the PMA process. The caveat is they will always wait until they see the data."

FDA doesn't want to risk public health by approving a device prematurely. However, in an industry where technology changes rapidly, its demands for data upon data still hamper innovation.

"For the small players, which have the ability to move faster, it's become difficult for some of that new technology to see the light of day because the FDA clearance or approval process can become so burdensome," she said.

On the other hand, FDA created a win with the presubmission program, which allows medical device manufacturers to interact with FDA to determine whether a submission is ready for substantive review. "I encourage all clients, particularly those seeking a PMA, to employ the presubmission process," Kvistad said. "Other than the time it takes to prepare documents, it's free, for now, and you get a read on where FDA's sensitivities lie. I've seen information from presubmissions used very well."

If FDA's various initiatives to streamline submission for certain medical devices come to fruition, it will benefit the medtech industry and the public. The question is whether FDA will take the risks needed to make it all happen.

"The quicker we can get products to patients the more likely insurers will approve the products," Sayer said. "The more we can accelerate technology and offer patients more choices, the better."

7 Moments That Transformed the Obesity Device Market

When the American Medical Association officially recognized obesity as a disease in 2013, it caused a shift and renewed vigor in  medtech solutions for the condition. Here are seven key events that transformed the device obesity treatment space. 

Topas COC helps mold next-gen wearable insulin delivery devices

Topas COC helps mold next-gen wearable insulin delivery devices

More than 30 million people in the United States are diagnosed with diabetes, and it is the most costly chronic disease in the country, according to the American Diabetes Association. It cost a total of $327 billion in 2017 to treat the condition in the United States, according to the association. Fortunately, medtech companies continue to harness technology to develop more-effective, patient-friendly devices to manage diabetes. Cyclic olefin co-polymers (COCs) from Topas Advanced Polymers (Florence, KY), a business of Polyplastics Co., Ltd., are playing a significant role in the development of these next-generation devices.

t:slim X2 insulin pump from Tandem
The t:slim X2 insulin pump from Tandem Diabetes Care Inc. lets users make treatment decisions without pricking
their finger.

Earlier this year, Topas announced that its COC was selected to mold the cartridge of the V-Go wearable insulin delivery device developed by Valeritas Holdings Inc. (Bridgewater, NJ). Today the company announced that another manufacturer of wearable insulin delivery pumps, Tandem Diabetes Care Inc. (San Diego, CA), has specified Topas 8007S-04 COC to manufacture the disposable cartridges for its device.

According to Topas, the material was selected over competitive thermoplastics because of its purity, drug compatibility, biocompatibility and dimensional stability. The drug-contact material delivers consistent, reproducible performance and facilitates miniaturization of drug delivery systems, said Topas, adding that it can be molded with zero draft for maximum precision of drug delivery.

Plastikos Inc. and sister moldmaking company Micro Mold, both located in Erie, PA, worked closely with Tandem to develop the molds and manufacture the cartridge parts. Plastikos reportedly is one of the leading medical molders of precision COC components for drug-delivery devices, with shipments of millions of parts during the past year.

Tandem’s simple-to-use t:slim X2 insulin pump is described as the smallest pump available and the only one capable of remote feature updates. It is the first continuous glucose monitoring device cleared by FDA that lets users make treatment decisions without pricking their finger. The t:flex insulin pump has capacity for up to 480 units, providing up to three days of insulin delivery with fewer interruptions for cartridge changes compared with other pumps, according to Tandem.

The pumps carry precision-molded disposable cartridges, several parts of which are molded of Topas 8007S-04. The components are manufactured under strict performance qualifications including challenging tolerance levels and multi-cavity tooling. They are produced in complex geometries and tight tolerances of less than 0.001 in. (0.025 mm).

Unlike other engineering thermoplastics or glass, Topas said that its COC offers a non-ionic, minimally reactive surface. This non-polar substrate does not promote adsorption, denaturation, aggregation or precipitation. With very low leachables and extractables, the glass-clear medical polymer preserves long-term drug purity, enabling better performance and patient safety, said Topas.

NPE2018: Frigel enhances Microgel RCP Chiller with digital controls

NPE2018: Frigel enhances Microgel RCP Chiller with digital controls

FrigelFrigel (East Dundee, IL) has extended its digital control technology to the Microgel RCP Chiller, giving processors in demanding polyethylene terephthalate (PET) preform and large-part blowmolding operations the ability to more effectively optimize productivity, profitability and quality. The company invites attendees of NPE2018 to see the Microgel RCP Chiller at booth S14085, located in the show’s first-ever Bottle Zone. 

Designed to deliver high-pressure and high-flow cooling water for individual processing machines, the Microgel RCP Chiller eliminates the need for central chiller systems in PET preform, large-part blowmolding and high-speed multi-cavity injection molding applications. The addition of digital controls gives users the ability to capture process-cooling energy consumption data and more easily adjust the unit to achieve optimal efficiency and cost savings. 

The enhancement to the Microgel RCP Chiller is another example of Frigel’s commitment to helping processors leverage process-cooling innovations to gain a clear-cut advantage, said Frigel North America Marketing Manager Al Fosco.

“The Microgel RCP Chiller is the only machine-side chiller that provides powerful cooling with high coolant pressure and flow throughout the mold, which is essential in PET preform and large-part blowmolding applications,” said Frigel North America Marketing Manager Al Fosco. “The addition of our digital controls meets another essential need by allowing processors to more readily access process cooling data, including energy data, over extended periods. As a result, processors are better able to cost-effectively and efficiently improve cycle times and consistently produce quality products in these demanding cooling applications.”

The Microgel RCP Chiller is among numerous Frigel innovations on display at NPE2018. Frigel’s presence at NPE extends beyond its booth with 32 Frigel units operating in 14 booths of leading plastics machinery manufacturers, which is unprecedented for any process-cooling equipment company. 

Frigel also announced the availability of HB-Therm Temperature Control Units (TCUs) in North America that use water—not synthetic oil—as a heat transfer fluid to cool plastic molds at operating temperatures of 200° to 230° C (392° to 446° F). The water HB-Therm TCUs deliver precise cooling while eliminating environmental concerns associated with oil TCUs, which are often used to achieve high operating temperatures. Additionally, water as a heat transfer fluid is an inherently safer option than synthetic oil.

Frigel will display the HB-Therm TCUs in booth W193.

Frigel North America has served as the exclusive distributor of HB-Therm TCUs in the United States and Canada for nearly a decade. HB-Therm AG manufactures the full line of TCUs at its operation in Gallen, Switzerland. The Swiss TCUs have proven to provide highly accurate temperature control in applications where precise cooling is essential. Examples include medical applications that require validation of process cooling temperatures and small, injection-molded precision parts. 

“With these high-temperature water TCUs, processors can maintain precise cooling at high temperatures without the environmental concerns normally associated with the use of oil as a heat transfer fluid,” Fosco said. “Water is also a more safe option than oil."

The high-temperature water HB-Therm TCUs complement the existing line of HB-Therm water TCUs rated to deliver and maintain process-cooling water from 100° to 180° C (212° to 355° F).

A war on plastic could backfire—will a war on plastic pollution fare any better?

A war on plastic could backfire—will a war on plastic pollution fare any better?

little green army menEarth Day was celebrated this past Sunday, reminding us all that the Earth and the resources we obtain from it are valuable. A recent article in BBC Business News, “War on Plastic May Do More Harm than Good, Warns Think Tank,” by BBC environment analyst Roger Harrabin, noted that, “A green think tank has warned of the risk of unintended consequences from the wave of concern about plastics.”

Let’s face it, a “war” on plastic and plastic products that we’re experiencing globally could backfire. When someone declares “war” on anything—whether it’s a product, a material, a people or a country—the other side fights back. War is never a good thing. That’s why the Green Alliance’s Libby Peake told BBC News, “Plastics are clearly a huge problem but we have concerns that legitimate public outrage will lead businesses and governments to rush into the wrong decisions.”

The Green Alliance wants to “transform the notion of a ‘war on plastics’ into a ‘war on plastic litter,’” said Harrabin. “The group, like many environmentalists, gave a grudging welcome to Chancellor Philip Hammond’s call for evidence on taxes on single-use plastics.”

A recent news item noted that drinking straws and other single-use items might be banned outright in Great Britain, as the country considers several “cures” for plastic litter. 

However, Harrabin noted that the Green Alliance warns that “rejecting all plastic food packaging could prove counter-productive,” given that food waste is also a big problem and the technologies in plastic packaging could help solve that.

New technologies such as barrier packaging would certainly be beneficial to the packaged food sector, and government officials need to take care that they don’t throw the baby out with the bath water. 

The Green Alliance is also concerned that substituting plastics with plant-based “bio-plastics” just might have a greater impact on the environment than conventional plastic. “Forests are already being felled to grow crops to feed the world’s booming demand for meat production, and wild land is also disappearing to produce bio-fuels for cars and electricity generation. But there is a finite amount of land,” Harrabin wrote, adding that the Green Alliance “fears that a demand for plastic substitutes could also increase the pressure for deforestation.”

Another organization that claims to be an opponent of a war against plastic is Upstream (Damariscotta, ME), which promotes “upstream” solutions. Its theme for Earth Day 2018 was “End Plastic Pollution.” However, according to the press release I received on April 22, Upstream promotes such ideas as:

  • Developing the unpackaged delivery business model for food-delivery systems toward sustainable, biodegradable materials, where packaging is necessary.
  • Continuing to work with partners to hold Starbucks accountable for single-use plastic pollution.
  • Planning the 2019 Plastics & Health Forum, convening scientists, environmentalists and medical experts to declare a “state of crisis” over the use of toxic plastics, “as the story of plastics and health has yet to be told."
  • Organizing a global #BreakFreeFromPlastic movement, bridging the story of microplastics to its petrochemical extraction source.

It sure sounds like Upstream is actually promoting the end to plastics’ use in a number of things. While not openly declaring war on plastic, you could say their war is against Starbucks. Everyone is beating up on Starbucks these days, primarily because there is so much misinformation and fake science in the news.

Harrabin points to the “backlash against plastics” that led Lego to announce that it would begin making its bricks from plastics “derived not from oil, but from sugar cane.” The media headline—“Lego goes green one brick at a time”—made for good press, but Harrabin noted that the company confirmed to him that “the ‘eco’ bricks would be made from polyethylene—that’s exactly the same chemical compound as plastic derived from oil (which, of course, came from plants millions of years ago).”

The Green Alliance’s Peake told Harrabin, “Turning plants into plastic in this way means that, at the end of life, it won’t be biodegradable and will have all the potential drawbacks of traditional plastic.” 

The Lego headline and other misleading, attention-grabbing news stories are examples of the continued fake science surrounding the use of plastic, which is ultimately, as Harrabin pointed out, a plant-based material. Intended solutions often lead to unintended consequences, as the Green Alliance’s Peake noted. “We must ensure that whatever solutions we design don’t increase emissions, damage world ecosystems or result in more waste,” she told Harrabin.

The war against plastics currently being fought against any company that uses plastic for single-use packaging is one that ultimately the plastics industry will have to fight against. By getting companies to stop using plastic in any form, these advocacy groups believe they will ultimately put the plastics packaging industry out of business. They might be right, if the industry doesn’t stand up and fight.

How to Conquer Medtech's Over-Documentation Problem

Pixabay How to Conquer Medtech's Over-Documentation Problem

Ever wonder why startups seem to develop new products so much faster than large, established medical device companies? One reason, according to a product development expert who spoke at BIOMEDevice Boston, is that startups only submit the minimum amount of quality management system (QMS) documentation.

Medical device development is 70% to 80% documentation, said Tom Waddell, CEO of the Waddell Group.

He used one company as an example, which he described only as a large medical device company based in the Minneapolis, MN area, that required roughly 1,000 to 1,300 documents to submit a class III device to FDA for a clinical trial even though the agency's requirements for such was really in the range of 350 documents, Waddell said.

"If you're in the company doing 1,000 documents to turn in to FDA and you actually figure out how to do just 350 you go from 15 months of documentation down into the range of two to three months of documentation," Waddell said.

That's just to take the device into the clinical trial phase though.

"First thing I look at is what's the objective of the project? Is it through a limited clinical study? Then you can start reducing your full-blown manufacturing documentation up front. Your QMS system, if it's designed to be flexible, will allow for that," Waddell said.

That's not to say that it's okay to shortcut the QMS system requirements when the product reaches the manufacturing phase, he clarified.

"Obviously, if the project comes back and it's a success you're going to have to go through and do all of those things to be able to launch this into full-blown manufacturing to get it to be released into the market," Waddell said. "It's kind of like taxes, you don't get to not pay them but you can defer them awhile."

But if a company has multiple projects occurring at the same time and wants to knock out the early steps as quickly as possible to determine which project should move forward, cutting out some of that documentation upfront is a good way to do that, explained Bill Betten, president of Betten Systems Solutions.

"In most cases, they want a tradeoff. 'I've got three good ideas and I need to check them out quickly and easily, so that's where we're seeing a lot of focus," Betten said. "If you've got a very deliberate and defined program that's A to Z, you can still cut a lot of it."

But he also recognizes that one size doesn't fit all.

"I've had plenty of customers show up and the first thing I ask is 'how you doing your [design history file] and if they look at me blankly I know exactly what kind of customer I've got and what I'm going to have to do and the message I'm going to have to give them," Betten said. "So document early, document often, but do the right amount of documentation for where you need to be and where you're going to go. We're not suggesting you throw it away completely."

Waddell and Betten also shared these tips for moving new products to market fast.

Proposed ISRI specifications for flexible PVC await comments

Proposed ISRI specifications for flexible PVC await comments

The Institute of Scrap Recycling Industries (ISRI; Washington, DC) Board of Directors considered and approved the addition of flexible PVC plastic scrap specifications to the "ISRI Scrap Specifications Circular" at its spring meeting on April 16, 2018, during the ISRI Convention and Exposition. This addition is intended to more accurately reflect the plastic scrap commodities currently being traded in the marketplace. Final approval of the additional specifications are awaiting a 30-day comment period.

The specifications for flexible PVC are as follows:

Description: Typically consists of molding, weather stripping, flexible tubing, purging, battery covers, medical tubing, auto decals, flexible films and sheeting. It is typically resistant to chemicals, non-porous and extruded. It can be found in long profiles and can be wound onto a reel.

Product: PVC bale

Source: Post-consumer or post Industrial (including pre-consumer)

Technical information: Durometer level less than 90A on the Shore scale. Shore durometer measurement devices can be used to measure the indention of a prescribed needle into the material. The test method conforms to ASTM D2240. Flexible PVC is typically measured using the A scale.

Contamination: Prohibitives—material not accepted at any level, 0% allowed:

  • PET plastic of any form
  • Medical and hazardous waste

Contamination material allowed at small percentages:

  • Plastics other than PVC such as HDPE, LDPE, PP, PS
  • Rigid PVC
  • Liquids
  • Paper and cardboard
  • Ferrous and non-ferrous metals
  • Glue, adhesives, sticky tape
  • Co-extruded materials
  • Reinforcement weaves and fabrics

As per ISRI’s Policy Manual, any party may submit to ISRI a written appeal of the ISRI Board’s approval of these changes up to 30 days after publication of this notice. Written appeals must provide a rationale and a request for action. Once finalized, the new specification will be included in ISRI’s "Scrap Specifications Circular," which provides industry guidelines for buying and selling a variety of processed scrap commodities, including ferrous, nonferrous, paper, plastics, electronics, rubber and glass.

Are the Odds Ever in Edwards' Favor in the TAVR Games?

Are the Odds Ever in Edwards' Favor in the TAVR Games?

With competition picking up in the transcatheter aortic valve replacement (TAVR) space, it's easy to wonder if Edwards Lifesciences will continue to be the market victor. The company's stock price dipped this week after Edwards posted first-quarter results that fell short of consensus expectations.

But to borrow a popular phrase from Suzanne Collins' Hunger Games trilogy, there is still plenty of reason to believe that the odds may be ever in Edwards' favor. Here are the key takeaways from the company's earnings call, as transcribed by Seeking Alpha, along with analyst comments.

1. Medtronic's royalty payment rate to Edwards has dropped.

As per the terms of the agreement, the royalty rate Medtronic pays Edwards dropped at the beginning of the year, which made for a tough year-over-year U.S. sales comparison in the first quarter. Edwards CFO Scott Ullem said the company expects the full year 2018 royalty from Medtronic to be $15 million to $20 million less than it was in 2017.

Ullem said a few million dollars of that royalty impact was realized in the first quarter and the rest of the impact should be "fairly evenly distributed during the rest of the year."

2. Edwards still has strong growth expectations in transcatheter heart valve therapy (THVT).

"We continue to expect our THVT full year 2018 underlying sales growth rate to be at the higher end of 11% to 15%," Ullem said.

CEO Mike Mussallem reminded analysts during the call that the comps in the second half of the year are not equivalent to the comps that exist in the first half, which is part of why the company is confident it will hit the higher end of that growth guidance for the full year.

Several product milestones in the pipeline, detailed below, also factor into that confidence.

"We just generally have momentum. We continue to believe that we have the most competitive product line and that we've got a real growing marketplace," Mussallem said. "The more we study this marketplace, the more we believe and have confidence in the fact that there are many untreated patients."

3. Sapien 3 Ultra could drop by the end of the year.

Despite an unanticipated regulatory delay in Europe for the Sapien 3 Ultra system, Mussallem said the company expects to complete enrollment in the additional trial patients this quarter, putting it on track to receive CE mark approval of the Ultra system in the second half of the year. Also, he said, "following discussions with FDA, we continue to feel confident in the U.S. approval of this system in late 2018."

4. Doctors in Europe love the new Centera valve, but they don't love the price.

In February, Edwards picked up a CE mark for its premium price, self-expanding Centera valve, which contributed a minimal amount of sales in the first quarter.

"Clinician feedback has been very positive for this innovative valve system, and we have begun a targeted introduction to strategically position this valve in specific European centers," Mussallem said.

Rick Wise, an analyst at Stifel, commented during the question and answer portion of the call that the doctors he's talked to about Centera have also spoken highly of the new valve.

"Everybody is saying incredibly stable deployment, incredibly high device success, low need for recapture or repositioning, I'm hearing great feedback," Wise said. "The pushback is on price."

And Edwards makes no apologies for the price point.

"We have decided to price this valve at a premium. As a matter of fact, even a premium to Sapien 3 and you know that Sapien 3 is at a premium to competitive valves," Mussallem said. "It just reflective of the fact that this is our latest technology and, we think, highly differentiated from what others see."

But, he added, "we're being very thoughtful about what centers we go to, and how fast, and we're focused on a really high level of procedural success."

The company also announced this week that FDA approved its U.S. pivotal trial to study the Centera valve for severe symptomatic aortic stenosis patients whose surgical risk is considered to be intermediate. Mussallem said Edwards expects to begin enrollment in the third quarter and that the single-arm study will involve nearly 1,000 patients with a one-year endpoint, including patients who will be enrolled in a bicuspid substudy.

The study will be conducted in current Edwards centers so it is not likely to result in incremental sales, he said, but it will increase the company's R&D spending.

5. Don't underestimate the low-risk opportunity.

Mussallem announced during the call that FDA approved a limited continued access protocol (CAP) of its PARTNER III trial for patients with severe symptomatic aortic stenosis whose surgical risk is considered to be low.

"Since the low-risk trial has completed enrollment, the study will allow for the ongoing treatment at selected clinical sites of a limited number of low-risk patients with a Sapien 3 transcatheter heart valve," he said. "We expect the CAP program to commence in the third quarter."

The company plans to release data from the PARTNER III trial in March 2019 and is on track to receive FDA approval of a low-risk indication late that year, Mussallem said.

Wells Fargo's Larry Biegelsen noted that the investor debate around the low-risk indication is less about the outcome, which is expected to be positive, and more about the opportunity and adoption.

"I think some people have questioned whether the low-risk population is already penetrated," Biegelsen said to Mussallem during the call. "And given your surgical heart valve business continues to grow, it would suggest to me that the answer is now."

The analyst also asked if there will be a greater importance of durability in the low-risk population (presumably because of patient age) and, if so, could that slow adoption?

"We think that low risk is a very significant opportunity," Mussallem said. "I think sometimes people get confused and they think that low risk means younger patients. And although that might seem to be the case, there's actually a high number of low-risk patients that are elderly, many in their 70s, 80s, and [older]. It's just the way the system works. So I think you shouldn't underestimate what happens."

He said that the company's sites, by and large, do stay on label, dispelling the theory that physicians fudge patients' risk categories in order to make them eligible for the procedure.

"We continue to believe that the estimates that we put out about the size of the market in 2021 and beyond are still if anything, conservative," Mussallem said.

6. Japan is the fastest-growing transcatheter heart valve region.

"We think Japan is a big opportunity," Mussallem said. "Adoption is still very early."

While he didn't know the number of Japan centers off hand, he said it is "certainly less than 150."

"They could use a lot more to be able to really penetrate the opportunity and we think that demand is going to continue to be strong for quite a while."

Inspire Puts Sluggish IPO Concerns to Bed with Filing

AhmadArdity/Pixabay Inspire Puts Sluggish IPO Concerns to Bed with Filing

Inspire Medical Systems is seeking to raise about $75 million through an initial public offering. The company said the IPO was for 5 million shares of its common stock and the price is expected to be between $14 and $16 per share. Inspire has been approved to list its common stock on the New York Stock Exchange under the ticker symbol “INSP.”

The Minneapolis-based company has developed a neurostimulation device that provides treatment for moderate-to-severe obstructive sleep apnea (OSA). The technology is a closed-loop solution that uses an algorithm to continuously monitor a patient’s breathing patterns and delivers mild stimulation to the hypoglossal nerve to maintain an open airway during sleep.

Inspire won FDA approval for the device in 2014. The company was formed in 2007 when the technology and a significant intellectual property portfolio were spun out of Medtronic.

Inspire generated sales of $28.6 million last year with a net loss of $17.5 million. The company said it estimates that there are about 17 million individuals in the U.S. with moderate to severe OSA.

“The market for OSA treatment is large and growing,” Inspire said in a Securities Exchange Commission filing. “We believe there is a significant population in the United States with moderate to severe OSA who are unable to use or get consistent benefit from CPAP and who are eligible for our Inspire therapy.”

Other companies have stepped up to develop OSA treatment products with varying degrees of success. For example, Apnex Medical was in the process of developing technology for the market, but it closed down in 2013 after the company deemed it unlikely that it would meet a primary endpoint in its clinical trial.

LivaNova announced it was getting into the market when it made a bid to acquire San Diego, CA-based ImThera for $225 million. London-based LivaNova had been an investor in ImThera since 2011.

ImThera's implantable OSA device is designed to stimulate multiple tongue muscles via the hypoglossal nerve, which opens the airway while a patient is sleeping. The company is currently evaluating the OSA implant in a pivotal trial to obtain FDA premarket approval.