After nearly a decade of development and millions of dollars invested, Arrow International (Reading, Pennsylvania), after nearly a decade of development and millions invested, said in early April that it will discontinue its LionHeart left ventricular assist system (LVAS) program and focus its resources on CoreAide continuous flow, ventricular assist device (VAD). It said that the CoreAide is a more promising product and that its board voted to discontinue the development, sales and marketing related to the LionHeart.
Earlier announcements issued by the company may have signaled that the LionHeart program was headed for an early retirement. Arrow reported about a year ago that it was deferring its U.S. Phase II clinical trial of the LionHeart and was waiting to see how the next generation of the device would fare in the European market, where it received CE-marking in 2003. The company originally received FDA approval of an investigational device exemption for a Phase I trial of the system more than three years ago, in early 2001.
While Carl Anderson Jr., CEO and chairman of Arrow, said that the LionHeart program established "a new level of technological achievement," which included winning the CE mark, the company concluded that the LionHeart program was not feasible economically after assessing the "time and investment required to maximize the potential of the LionHeart" and that it "would not realize adequate returns for Arrow shareholders in an acceptable period of time."
Arrow will continue the clinical trial of its CoreAide continuous flow ventricular assist device in Europe, the development rights acquired through a licensing agreement with the Cleveland Clinic Foundation (Cleveland) in 2001. The company said it believes the CoreAide's smaller size, less-invasive surgical approach and inherently simpler design offers better opportunities for broader market acceptance. Similar to the Debakey VAD from competitor MicroMed (Houston), the CoreAide is non-pulsatile and features a magnetically suspended pumping mechanism and uses the moving blood as its lubricating system.
Other companies involved in the VAD sector include: A-Med Systems (West Sacramento, California), Thoratec (Pleasanton, California), WorldHeart (Oakland, California), Vascor (Pittsburgh) and VentraCor (Sydney, Australia).
Cardio firms line up for IPOs
Medical technology's initial public offering (IPO) opportunities continue to rebound in 2005, with companies in the cardiovascular sector among those dipping into the IPO pie.
CryoCor (San Diego), a developer of technologies to treat cardiac arrhythmias, last month filed with the SEC for an IPO of up to $46 million, with the number of shares offered and estimated price range not disclosed. The company said that the offering proceeds would be used to continue product development and ongoing clinical trials, build sales and marketing capabilities, provide working capital and go to other general corporate purposes.
CryoCor's products use cryogenic technology to treat arrhythmia, a disorder of heart rate or rhythm which causes the heart to pump blood less efficiently and can result in a stroke. The offered shares will list on the Nasdaq under the symbol CRYO.
ev3 (Plymouth, Minnesota) also filed with the SEC last month, but did not list the number of shares proposed or the pricing. Underwriters of the offering are Piper Jaffray & Co. and Banc of America. ev3 was founded in 2000 by Dale Spencer, an executive experienced in the endovascular device industry, and Warburg Pincus and The Vertical Group. Flying somewhat under the marketing radar, ev3 has been acquiring and developing a variety of catheter-based technologies used in the treatment of coronary, neurological and peripheral vascular diseases. A number of these products are still in clinical trials.
Its cardiovascular products include the SpideRx, a rapid-exchange filter for embolic protection; the X-Sizer, a thrombus removal system; the Diver C.E., a rapid exchange aspiration catheter; and the PLAATO, for minimally invasive occlusion of the left atrial appendage. It is developing a variety of stents used in the peripheral vasculature: a family of Prot g devices; AqWire, Nitrex and Gooseneck snares; and a family of balloon angioplasty catheters.
In its SEC filing, the company said it dependent on its Prot g GPS family of peripheral stents, "which generated more than 10% of ... net sales in fiscal 2004." It said also that in March in received notice from Medtronic Vascular that "it believes our Prot g stent infringes on one or more of its patents ..." ev3 will file for quotation on Nasdaq under the symbol EVVV.
AtriCure (West Chester, Ohio) made an IPO filing with the SEC for up to $57.5 million, but did not re-port the number of shares or their pricing.
AtriCure develops surgical devices designed to safely, rapidly and reliably create precise lesions in soft tissues. Cardiothoracic surgeons have adopted the AtriCure bipolar ablation system as an off-label treatment to create lesions in cardiac tissue to block the abnormal electrical impulses thought to cause atrial fibrillation.
UBS Investment Bank and Piper Jaffray & Co. are acting as joint book-running managers of the offering, and Thomas Weisel Partners and A.G. Edwards are acting as co-managers.
Abbott's ZoMaxx gets conditional IDE
Abbott Vascular (Redwood City, California), a division of Abbott Laboratories (Abbott Park, Illinois), said it has received conditional approval from the FDA for its investigational device exemption (IDE) application for the ZoMaxx drug-eluting stent (DES). As a result, Abbott reported that it soon will begin enrolling the first 250 patients into its ZOMAXX II clinical trial in the U.S. Launch of enrollment is consistent with anticipated U.S. approval for ZoMaxx in the second half of 2007, the company said.
ZOMAXX II will enroll 1,670 coronary artery disease patients at up to 80 centers and will compare outcomes in patients who are treated with Abbott's investigational ZoMaxx DES with those receiving Boston Scientific's (Natick, Massachusetts) Taxus Express2 DES. The primary endpoint of ZOMAXX II is nine-month, ischemia-driven, target vessel revascularization, a clinical measure of the need to conduct another intervention (such as stent, brachytherapy or surgery) to reopen a vessel previously treated with a stent.
"Abbott is committed to develop the ZoMaxx drug-eluting stent as an important new treatment for coronary artery disease patients worldwide," said Robert Hance, president of Abbott Vascular. "The ZoMaxx drug-eluting stent is poised to become an important product in Abbott Vascular's growing line of vessel closure, coronary and endovascular products."
Outside of the U.S., Abbott continues to enroll patients in ZOMAXX I, a 400-patient prospective randomized clinical trial that is being conducted in more than 30 centers in Europe, Australia and New Zealand. ZOMAXX I also compares the ZoMaxx stent to the Taxus.
The ZoMaxx DES consists of three key components: a flexible stent platform called TriMaxx, designed to facilitate ease of placement; a polymer-carrier called Pharmacoat, intended to enable steady drug elution; and an immunosuppressant drug from Abbott called ABT-578, shown to reduce vessel re-narrowing.
XDx launches heart transplant assay
XDx (South San Francisco, California) last month launched a test for the management of heart transplant patients in the hope that it will eliminate the need for potentially dangerous or problem-ridden biopsies, the current method of determining if a heart transplant patient is rejecting the donor organ. The test was launched at the annual meeting of the International Society for Heart and Lung Transplantation's (Addison, Texas) in Philadelphia, where physicians demonstrated the use of what XDx calls AlloMap molecular expression testing. The company said that, as such, it is "one of the first practical applications of the human genome project.
Heart transplantation is where "the need is the greatest," CEO Pierre Cassigneul told Cardiovascular Device Update. "It's a very high-stakes situation where it's literally a matter of life and death for patients, and the current methods of biopsy are not satisfactory for clinicians. So we felt that the need was compelling and also provided us with certain advantages for a start-up company."
The current clinical practice for monitoring heart transplant rejection is endomyocardial biopsy, requiring a sample tissue to be clipped from the heart and then analyzed. With AlloMap testing, which received CLIA approval in November 2004, a clinician draws a tube of blood and sends it to the XDx reference lab. "They process it, because we need to extract the cells from the blood sample immediately, because ... the immune system in the blood continues to express the gene, so we need to stop that reaction, extract the cells, and they are sent by FedEx overnight to us," Cassigneul said.
The XDx lab begins its processing of the patient's blood the day it is received, and following quality control procedures the following day, the lab provides a report to the clinician, about 48 hours for the whole process. That is also the typical time needed to complete the traditional endomyocardial biopsy. The XDx test, however, distinguishes rejection vs. lack of rejection, also known as quiescence, by detecting mobilization of the alloimmune response, rather than through graft damage with biopsy. XDx also says that its test may detect rejection that could not be determined through a graft.
To develop AlloMap testing, the company evaluated more than 25,000 gene sequences and, using microarray and real-time polymerase chain reaction technology to measure gene expression, developed a 20-gene algorithm specifically correlated with rejection. The AlloMap test translates gene expression information into "a single, actionable score," says XDx.
While cardiologists have been "incredibly successful at managing" their transplant patients, said Cassigneul the survival rate at 10 years is about 50% it usually is enabled by the use of potent immunosuppressive drugs. Those drugs, at about 10 years after the transplant, frequently begin causing problems for the patient, including infection and cancer, because their immune system has been suppressed in order to avoid rejection of the implanted heart. So, another goal of the test is to help cardiologists titrate the drugs, so that patients only get the least amount that they need to both prohibit rejection, yet avoid potential long-term side effects of the medication.
Cassigneul said that many payers already are reimbursing for the test. "The important thing is that the Allomap has been designed and priced so that it would actually generate cost savings to the system. Even though it's new technology [it] costs less than the current system of biopsies." XDx also is planning to use its technology to be used on all autoimmune diseases, such as rheumatoid arthritis and Crohn's disease, which multiplies the number of patients affected to about 20 million.
PolyHeme passes 3rd Phase III analysis
The stock of Northfield Laboratories (Evanston, Illinois) last month soared upward by 23% the day after an independent data monitoring committee (IDMC) gave its go-ahead to the ongoing Phase III trial of its PolyHeme product, a hemoglobin-based oxygen therapeutic. The approval marks the first time an oxygen therapeutic of this type has surpassed the third planned interim analysis milestone without requests for modification to a trial in high-risk trauma patients. The committee's decision was based on blinded mortality data in the first 250 people enrolled, Northfield said. "This is a validation of everything to date, and we are very gratified to have reached this point," said Steven Gould, chairman and CEO of Northfield.
The IDMC also performed a blinded power analysis to determine if an increase in the sample size was needed, based on a comparison of the predicted mortality rate with the mortality rate observed in the trial to date. The committee concluded that the original 720 patients planned for enrollment is sufficient.
The Phase III study is designed to evaluate PolyHeme when administered to patients in hemorrhagic shock following traumatic injury. The primary endpoint is survival at 30 days, and patients are being enrolled at Level 1 trauma centers throughout the U.S.
"A hemoglobin-based oxygen therapeutic is being used for the first time in this country at the scene of injury," Gould told Cardiovascular Device Update's sister publication, BioWorld Today. "That's what is so revolutionary about this trial."
PolyHeme is a solution of chemically modified hemoglobin that requires no cross matching and is compatible with all blood types. It has a shelf life of more than 12 months. The FDA has never approved a blood substitute.
High-risk trauma patients typically need transfusions, but blood is not carried in ambulances. While saline solution is used to replace blood loss, it does not carry oxygen to the body's tissues. Thus, PolyHeme could act as a substitute in situations of life-threatening blood loss. A competing firm in the oxygen therapeutic arena, Biopure (Cambridge, Massachusetts), has developed Hemopure in the clinic since the 1980s. It filed a biologics license application in 2002, but the FDA requested more work. Last month, the company completed enrolling patients undergoing elective coronary angioplasty in a Phase II European trial.
PolyHeme now has moved beyond the first three interim analyses conducted after 60, 120 and 250 patients were enrolled in the Phase III trial and followed for 30 days by the IMDC. The next evaluation will take place once 500 patients are enrolled. Northfield puts the market for high-risk trauma patients at $500 million in the U.S. Phase III enrollment of the 720 patients should be complete by the end of this year, and Northfield could file for approval in the U.S. sometime in 2006.
PolyHeme started out as a research project, funded by the Department of Defense and the U.S. Army, in the late 1960s. When the work produced a product that appeared to have clinical utility and commercial potential, Gould and four other scientists founded Northfield in 1985. Northfield said it intends to market the product alone in the U.S. and could expand the market from high-risk trauma to elective surgery or oncology.
The worldwide market potential for PolyHeme is estimated at between $1 billion and $2 billion for all indications.