Thoratec

Thoratec Corporation

Type	Public
Industry	Medical devices
Founded	California, U.S.(March 1, 1976 (1976-03-01))
Headquarters	Pleasanton, California
Area served	Global
Key people	D. Keith Grossman President, CEO and Director Taylor Harris CFO
Products	HeartMate XVE HeartMate II
Revenue	USD (million) 313 (2008)
Operating income	USD (million) 26 (2008)
Number of employees	1,110
Divisions	ITC
Website	Thoratec.com

Thoratec Corporation is a United States-based company that designs, manufactures, sells, and supports products that treat a wide range of clinical needs for advanced heart failure patients, specifically proprietary medical devices for circulatory support, vascular graft applications, point-of-care diagnostic test systems, and skin incision products. Headquartered in Pleasanton, California, U.S.A., its product lines include the Thoratec VAD (Ventricular Assist Device) and HeartMate LVAS (Left Ventricular Assist System). Thoratec’s devices are implanted in patients with advanced heart failure worldwide.^[1]

For patients with acute heart failure, Thoratec markets the CentriMag Blood Pumping System, which is manufactured by Levitronix LLC and distributed by Thoratec in the U.S. under a distribution agreement with Levitronix.

Thoratec’s shares were listed on NASDAQ on May 18, 1981.

History

Thoratec Corporation was incorporated in California in March 1976 under the name Thoratec Laboratories Corporation. The name was changed to Thoratec Corporation in 2001 at the time of a merger with Thermo Cardiosystems, Inc., a manufacturer of cardiac assist, blood coagulation testing, and skin incision devices. The merger was completed on February 14, 2001.

On September 11, 2001, Tom Burnett (COO of Thoratec) and other passengers aboard overpowered the hijackers of United Airlines Flight 93, forcing the terrorists to bank and crash into an open field, killing everyone on board.

Medical and patient community

Thoratec’s cardiovascular division VAD products primarily serve patients suffering from late-stage heart failure. In the United States:^[2][3]

• About 5.7 million Americans suffer from chronic heart failure (CHF),
• more than 600,000 new cases are diagnosed each year, and
• it is responsible for over 280,000 deaths annually.
• Close to $35 billion in direct and indirect costs were attributed to heart failure in 2008.

For most patients, heart transplantation is the most effective treatment for survival. However only 2,100 advanced-stage heart failure patients receive heart transplants while some 250,000 have to explore other treatment options. Mechanical circulatory support (MCS) with a ventricular assist device (VAD) is used to boost hemodynamic function in hearts and is a suitable option for patients as a bridge to transplantation support device.^[4][5]

While surgery is not a frequently used treatment, it is a necessary treatment for certain patients who cannot be helped with medication or dietary and lifestyle changes.

In a small number of cases left ventricular assist devices, combined with drug therapy, have enabled the patient’s heart to recover sufficiently for the device to be able to be removed (explanted).^[6]

Thoratec works directly with cardiologists, surgeons and VAD coordinators in a variety of ways, from building community awareness and developing education materials regarding MCS therapy, to providing training and patient support. Thoratec offers educational and charitable grants for advancing MCS therapy as well.

Products

Thoratec offers a broad range of mechanical circulatory support devices. The Company is focused on developing new technologies and the approval of new therapy and product indications for its current products.^[7]

• HeartMate II - The HeartMate II is a left ventricular assist device (LVAD) that is implanted alongside a patient’s native heart with the purpose of pumping for the heart’s left ventricle. The HeartMate II is surgically implanted just below the diaphragm in the abdomen and attached to the aorta, leaving natural circulation in place as it assists in providing energy to propel blood throughout the body as a healthy left ventricle would. The HeartMate II is designed to have a longer functional life than the previous generation of devices and to operate more quietly. Patients with the HeartMate II can be discharged from the hospital and the portability of the device’s components makes it easier for the patient to remain active. The FDA approved the HeartMate II for bridge to transplantation Therapy in April 2008 and for destination therapy in January 2010.^[7][8][9]
• HeartMate XVE – The HeartMate XVE is a left ventricular assist system (LVAS) that is implanted alongside a patient’s native heart with the purpose of pumping for the heart’s left ventricle. The HeartMate XVE is surgically implanted just below the diaphragm in the abdomen and attached to the aorta, leaving natural circulation in place as it assists in providing energy to propel blood throughout the body as a healthy left ventricle would. The FDA approved the HeartMate XVE for Bridge to Transplantation Therapy in December 2001 and for Destination Therapy in April 2003. The device has wearable components, which include the system controller and two rechargeable batteries. This allows patients to be discharged from the hospital. For patients that do not qualify for heart transplants, the HeartMate XVE is a viable option to extend their life expectancy. The HeartMate XVE is the only system available that does not require systemic anticoagulation.^[7][8]
• PVAD (Paracorporeal Ventricular Assist Device) is an external, pulsatile, ventricular assist device, that was FDA-approved for Bridge to Transplantation (BTT), including home discharge, and post-cardiotomy recovery, and provides left, right or biventricular support. The PVAD is also the basis for further Thoratec product innovations.^[10]
• IVAD - Based on the Thoratec PVAD, the IVAD (Implantable Ventricular Assist Device) is an implantable, pulsatile, ventricular assist device, that was FDA-approved for BTT, including home discharge, and post-cardiotomy myocardial recovery, and provides left, right or biventricular support.^[11]

Research and development

Milestones

• In 1994, the U.S, Food and Drug Administration (FDA) approved the HeartMate IP LVAD for bridge to transplantation, the first commercially implantable LVAD in the United States. The HeartMate IP was an implantable pneumatic LVAS powered by an external electrically driven air-pump.^[12]
• The HeartMate IP received the European Conformity Mark (CE Mark) in April 1994 and the Canadian approval August 1998.
• In late 1995, the FDA approved the protocol for conducting clinical trials of the HeartMate VE LVAS as an alternative to medical therapy in the REMATCH trial.
• In May 1998, the first patient was implanted with a HeartMate VE LVAS as part of the REMATCH trial.
• The HeartMate VE, an electric LVAS that is driven by an implanted electric motor and powered by a lightweight battery pack worn by the patient, received FDA approval for commercial sale in September 1998.
• In 2001, the landmark, REMATCH trial was successfully completed and led to the FDA approval of the use of the HeartMate SNAP-VE LVAS as destination therapy for patients who are NYHA Class IV patients with end-stage ventricular failure with certain specific criteria, i.e., that they have received optimal medical therapy for at least 60 of the last 90 days; have a life expectancy of less than two years; and are not eligible for cardiac transplantation.
• The HeartMate XVE was CE Mark authorized for bridge to transplantation and for destination therapy in June 2003.
• The HeartMate XVE was approved by the FDA for bridge to transplantation in December 2001 and the first LVAD approved for destination therapy in April 2003.
• The PVAD (paracorporeal ventricular assist device) was the first biventricular support system approved by the FDA in 2004 for home discharge, meaning patients could go home with the system to await heart transplantation or for their native heart to recover.
• The Thoratec HeartMate II was CE Mark authorized for bridge to transplantation and for destination therapy in November 2005.
• The Thoratec HeartMate II was approved by the FDA for bridge to transplantation in April 2008.

In July 2009, the Journal of the American College of Cardiology reported on 18-month follow-up data for the HeartMate II LVAS Pivotal Study, which showed improved survival, less frequent adverse events and greater reliability with continuous flow LVADS compared to pulsatile flow devices.^[13]

Innovations

The HeartMate family of devices illustrates a continuum of technological upgrades in the VAD market:

• Thoratec HeartMate II is among the most predominant continuous flow VADs in the market.
• Thoratec HeartMate XVE is one of the most used LVADs in the world.
• Thoratec has the only FDA-approved LVAD for Destination Therapy, or permanent support.
• Thoratec is the only company in the sector with four approved VADs.
• Thoralon is a proprietary biocompatible material developed at Thoratec that minimizes blood clotting and inflammation.
• The HeartMate XVE is designed with Thoratec’s proprietary textured blood contacting surfaces, which results in a reduced incidence of clot formation and thromboembolism, thereby removing the need for anticoagulation therapy. This is the only system available that does not require systemic anticoagulation .

Studies

Destination study, Heartmate II

At a late session during the November 17, 2009 American Heart Association's scientific sessions, investigators presented data from a two-year randomized trial where patients with advanced heart failure who were ineligible for a heart transplant were implanted with either a HeartMate XVE pulsatile LVAD (66 patients) or the HeartMate II continuous flow LVAD (134 patients). The median age was 64 years (range, 26-81) and the primary end-point was at two-years, survival free from disabling stroke and reoperation. Thirty-eight centers in the US participated in the study, led by Duke University and the University of Louisville.^[14]

Results included the following:^[15][16]

1. Patients implanted with the HeartMate II experienced less frequent adverse events and device replacements, and had a better quality of life and functional capacity.

1. Two-year survival rate more than doubled among the HeartMate II patients. Specifically, after one year, 68 percent of those with the HeartMate II implanted were still alive, compared with 55 percent of those who received the older LVAD. At two years, results were more dramatic with 58 percent of those who received the HeartMate II were still alive, compared with 24 percent of those implanted with the older LVAD.
2. Quality of life for the HeartMate II patients improved, as shown by their ability to walk twice as far as those with the older LVAD.
3. Forty-six percent of patients, at the two year primary end point, were still alive, had not suffered a stroke and did not need to have the device replaced, compared with 11 percent who received the older LVAD.

The study concluded that treatment for the destination therapy indication with the HeartMate II significantly improved the probability of survival free from stroke and device failure at two years.

HeartMate II LVAS Pivotal Study

The most recent outcomes for mechanical circulatory support therapy are from the HeartMate II LVAS Pivotal Study. The pilot trial for the HeartMate II LVAS began in November 2003 and consisted of 46 study patients at 15 centers.^[17]

The HeartMate II Pivotal Study began in 2005 and included the evaluation of HeartMate II for two indications: Bridge to Transplantation (BTT) and Destination Therapy (DT), or long-term, permanent support. It was the first time the FDA had approved a clinical trial to include both indications in one protocol.^[17]

The HeartMate II Pivotal Study is the largest study of VADs ever conducted, with more than 1,000 patients who have been implanted with the device. In total, more than 3,000 patients have received the device both in the clinical trial and since its commercial availability for BTT, following FDA approval in April 2008.^[17]

The FDA approval of HeartMate II for BTT was based on one year follow-up data from the first 194 patients enrolled in the trial. Clinical evidence supports positive survival outcomes and improved quality of life for a broad range of patients.^[17]

Eighteen-month follow up data on 281 patients who had either reached the study end-point or completed 18 months of post-operative follow-up showed improved survival, less frequent adverse events and greater reliability with continuous flow LVADS compared to pulsatile flow devices. Of the 281 patients, 157 patients had undergone transplant, 58 patients were continuing with LVADs in their body and seven patients had the LVAD removed because their heart recovered; the remaining 56 had died. The results showed that the NYHA Class of heart failure the patients had been designated had significantly improved after six months of LVAD support compared to the pre-LVAD baseline. Although this trial involved bridge to transplantation indication, the results provide early evidence that continuous flow LVADs have advantages in terms of durability and reliability for patients receiving mechanical support for destination therapy.^[17]

REMATCH

The REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) clinical trial began in May 1998 and ran through July 2001 in 20 cardiac transplant centers around the country. This landmark trial was designed to compare long-term implantation of left ventricular assist devices with optimal medical management for patients with end-stage heart failure who require, but do not qualify to receive cardiac transplantation. As a result of the clinical outcomes, the device received FDA approval for both indications, in 2001 and 2003, respectively.^[18]

The trial demonstrated an 81% improvement in two-year survival among patients receiving HeartMate XVE versus optimal medical management. In addition, a Destination Therapy study following the REMATCH trial demonstrated an additional 17% improvement (61% vs. 52%) in one-year survival of patients receiving the HeartMate XVE, with an implication for the appropriate selection of candidates and timing of VAD implantation.^[18]

A test carried out in 2001 by Dr. Eric Rose and REMATCH study group using patients with Congestive Heart Failure who were ineligible for a transplant showed a survival at two years of 23% for those implanted with an LVAD compared with 8% for those who were given drug treatment. The two major complications of VAD implantation were infection and mechanical failure.^[18]

According to a retrospective cohort study comparing patients treated with a left ventricular assist device versus inotrope therapy while awaiting heart transplantation, the group treated with LVAD had improved clinical and metabolic function at the time of transplant with better blood pressure, sodium, blood urea nitrogen, and creatinine. After transplant, 57.7% of the inotrope group had renal failure versus 16.6% in the LVAD group; 31.6% of the inotrope group had right heart failure versus 5.6% in the LVAD group; and event-free survival was 15.8% in the inotrope group versus 55.6% in the LVAD group.^[18]

HARPS Study

The Harefield Recovery Protocol Study (HARPS) is a clinical trial to evaluate whether advanced heart failure patients requiring VAD support can recover sufficient myocardial function to allow device removal (explantation). HARPS combines the HeartMate XVE with conventional oral heart failure medications, followed by the novel β2 agonist clenbuterol. This allows investigators to examine a strategy that may have enormous benefit for advanced heart failure patients: being able to forgo heart transplantation.^[19]

Birk's results to date:^[19]

• 73% (11 of 15) of patients who underwent the combination therapy regimen demonstrated sufficient recovery to allow explantation and avoid heart transplantation.
• Freedom from recurrent heart failure in surviving patients was 100% and 89% at one and four years after explantation, respectively.
• Average ejection fraction was 64% at 59 months after explantation; all patients were NYHA Class I.
• No significant adverse effects were associated with clenbuterol therapy.

Controversies

On August 3, 2004, a class action was filed against Thoratec, alleging that during the Class Period, defendants made false and misleading statements regarding the market for HeartMate. A settlement of $3,375,000 was reached in 2006.^[20]

Corporate structure

Thoratec develops, manufactures and markets proprietary medical devices used for MCS for advanced heart failure. The Thoratec product line includes the PVAD and IVAD and the HeartMate product line includes the HeartMate XVE and HeartMate II. The Company also markets the CentriMag Blood Pumping System, manufactured by Levitronix. Thoratec also manufactures a vascular access graft for renal dialysis.^[21]

Thoratec is focused on maintaining and expanding their leadership position. This includes offering a broad range of products, focusing on and partnering with leading heart centers, expanding the use of VADs in existing segments, increasing the Company’s presence in Cardiovascular and ITC segments, obtaining approval for and developing new products, and increasing the cost effectiveness of the therapies that employ Thoratec’s products.^[21]

Thoratec Corporation’s main executive officers are:^[22]

• D. Keith Grossman, President and Chief Executive Officer
• Taylor Harris, Vice President and Chief Financial Officer
• David A. Lehman, Senior Vice President and General Counsel
• Vasant Padmanabhan, Senior Vice President, Technical Operations

The Company’s Board of Directors consists of nine members:

• Neil F. Dimick, Chairman of the Board
• D. Keith Grossman
• J. Daniel Cole
• Steven H. Collis
• William A. Hawkins, III
• Paul A. LaViolette
• Martha H. Marsh
• Todd C. Schermerhorn

Locations

Thoratec is headquartered in Pleasanton, California, and has manufacturing facilities in Burlington, Massachusetts;Rancho Cordova, California; Edison, New Jersey; and Cambridgeshire, United Kingdom.^[21]

VADs and grafts for the Cardiovascular Division are manufactured at Thoratec’s Pleasanton headquarters.

Mergers and acquisitions

In February 2001, Thoratec completed a merger with Thermo Cardiosystems Inc. (AMEX: TCA), a Massachusetts-based manufacturer of cardiac assist, blood coagulation testing, and skin incision devices. It was at the time of the merger that Thoratec changed its name from Thoratec Laboratories Corporation to Thoratec Corporation.

In February 2009, Thoratec entered into a merger agreement to acquire HeartWare International (Nasdaq: HTWR) in a transaction valued at approximately $282 million. On July 31, 2009, Thoratec and HeartWare announced the termination of the agreement, citing strong opposition from the Federal Trade Commission.

In January 2010, Thoratec acquires catheter-based heart pump technology from Getinge. Thoratec is expected to pay Getinge a cash purchase price of $8.5m for the technology, which is a minimally invasive, acute cardiac axial flow pump.^[23]

References