Roto-rooter preliminary results out. Look good to me for very early stage results. Notice they got statistical significance with a small sample size even though the very low-dose group got lumped in with the rest of the treated group.
Peter
Pharmacyclics' ANTRIN(TM) Demonstrates Activity in Photoangioplasty Treatment Of Atherosclerosis
PR Newswire - November 09, 1998 12:52
Interim Phase I Data Presented at American Heart Association Meeting
SUNNYVALE, Calif., Nov. 9 /PRNewswire/ -- Pharmacyclics, Inc. (Nasdaq: PCYC) today announced that interim results from its phase I study with ANTRIN(TM) photoangioplasty for patients with atherosclerotic peripheral arterial disease were reported at the meeting of the American Heart Association (AHA) in Dallas, Texas.
Eighteen patients were treated in the ongoing phase I study conducted at Stanford University Medical Center, Division of Cardiovascular Medicine. The trial was designed primarily to evaluate the safety of ANTRIN followed by photoangioplasty in patients with severe symptomatic arterial insufficiency involving the major arteries of the lower extremities. Successive groups of patients received a single treatment with increasing doses of ANTRIN followed 24 hours later by photoangioplasty of a critical lesion. Patients were evaluated both for systemic toxicity and local arterial responses by follow-up intravascular ultrasound (IVUS) and angiograms either fourteen days or twenty-eight days following photoangioplasty. ANTRIN was given intravenously and light was delivered to the diseased artery through a 0.89mm optical fiber catheter using standard percutaneous endovascular techniques.
Fourteen patients were evaluated with IVUS and/or angiograms; follow-up studies are pending in two patients and not available in two other patients. In twelve patients who received follow-up IVUS, nine patients responded to treatment defined as an increase of greater than 10% in the blood vessel opening (minimal luminal diameter, "MLD"). Responding patients had increases in MLD ranging from 10% to 74%. The differences between pre- and post-treatment MLDs for the twelve patients evaluated by IVUS were statistically significant, p<0.02.
Fourteen patients received follow-up angiograms and seven demonstrated a reduction in stenosis in the treated lesions. These responses were seen in the patients receiving higher doses of ANTRIN. The differences between pre-and post-treatment stenosis for the fourteen patients evaluated with angiograms were statistically significant, p<0.05.
Various doses of ANTRIN were evaluated and no serious treatment-related adverse reactions or vascular toxicities have been observed. At the higher doses, some patients reported mild and transient tingling sensations in the tips of their fingers, nose or ears, or skin reactions which were thought to be associated with exposure to sunlight.
The presentation was given by Stan Rockson, M.D., a cardiologist at Stanford. "ANTRIN photoangioplasty was well-tolerated and we were very pleased to see evidence of activity. ANTRIN photoangioplasty appears to be a novel approach for endovascular treatment of atherosclerosis and restenosis, or it may augment existing endovascular procedures such as balloon angioplasty," stated Dr. Rockson.
Pharmacyclics also announced that it has opened a second clinical trial site for its phase I study at the Mid-America Heart Institute in Kansas City, Missouri. Based on the interim results of the phase I study, eligibility has been expanded to include patients with arterial insufficiency involving the major vessels of the lower extremities up to the level of the aortic bifurcation. The study will now evaluate the safety and efficacy of increasing doses of light delivered to the diseased artery.
"These clinical results go beyond what we expected to accomplish at this early stage," stated Richard A. Miller, M.D., president and CEO of Pharmacyclics. "We plan to complete the phase I trial within the next three months and we will then continue clinical development of this treatment in both peripheral and coronary artery diseases."
Pharmacyclics also reported, in a companion paper delivered at AHA, that ANTRIN photoangioplasty was found to be effective in treating atherosclerosis and restenosis in preclinical models. These studies demonstrated that ANTRIN photoangioplasty reduced atherosclerosis without causing endothelial damage or trauma to the vessel wall. The Pharmacyclics studies determined that the mechanism of action for ANTRIN photoangioplasty is based on its ability to eliminate macrophages, a scavenger inflammatory cell in atherosclerotic lesions. Macrophages are believed to be one of the culprit cells in atherosclerosis and restenosis.
ANTRIN is a water-soluble photosensitizer that accumulates in atherosclerosis, is cleared rapidly from the blood and is activated by 732nm light, a wavelength that is able to penetrate through blood. This property enables the treatment of atherosclerosis or restenosis without interruption of blood flow. Once localized in the diseased vessel, ANTRIN may be activated by endovascularly-delivered light using an optical fiber inserted in the vessel.
In contrast to mechanical procedures such as balloon angioplasty, ANTRIN photoangioplasty appears to reduce atherosclerosis without damaging the endothelium and without damaging the vessel wall, both important factors leading to restenosis. Long segments of diseased vessels may be treated, a potential advantage over existing angioplasty techniques which are limited to the treatment of relatively short segments.
Atherosclerosis results from the accumulation of cholesterol, macrophages and smooth muscle cells in the walls of blood vessels. This often results in narrowing of the lumen and reduction of blood flow. In the coronary arteries (arteries that supply the heart with blood), atherosclerosis can result in angina or heart attacks. In the cerebrovascular circulation (arteries supplying blood to the brain) atherosclerosis may result in stroke, and in the peripheral circulation it may result in ischemia leading to decreased function and ultimately loss of limbs.
Currently, atherosclerosis is treated with medical therapy, surgery or endovascular procedures such as balloon angioplasty. There are approximately 600,000 coronary angioplasty procedures performed annually in the U.S. and another 150,000 such procedures performed in the lower extremities. Angioplasty is complicated by the development of restenosis, or the renarrowing of blood vessels, in a significant number of patients, which has led to the widespread use of stents. Although stents are effective in opening the vessel, this procedure has only partially addressed the problem.
IVUS is a procedure used to evaluate the inside of arteries and is performed by inserting an ultrasound transducer within the lumen of the blood vessel. Using this diagnostic technique, it is possible to measure the size of the lumen or the degree of obstruction within a vessel. IVUS can also be used to evaluate the characteristics of the blood vessel wall. It is commonly used to assess atherosclerosis and response to therapeutic interventions. Angiograms are performed by injecting X-ray contrast media into blood vessels and are also used to evaluate abnormalities of blood vessels. Generally, angiograms are less sensitive and less quantitative than IVUS.
Pharmacyclics is a pharmaceutical company developing energy-potentiating drugs to improve radiation therapy and chemotherapy of cancer, and to enable or improve the photodynamic therapy of certain cancers, atherosclerotic cardiovascular disease and diseases of the retina. The company's products are ring-shaped small molecules, called "texaphyrins," which are patented agents derived from Pharmacyclics' versatile technology platform for designing and synthesizing energy-potentiating drugs. These texaphyrins localize in cancer cells and atherosclerotic plaque, where they can be activated by forms of energy, including X-ray, chemical and light, to eliminate diseased tissue.
The statements made in this press release may contain certain forward-looking statements that involve a number of risks and uncertainties. Actual events or results may differ from the company's expectations. In addition to the matters described in this release, future actions by the U.S. Food and Drug Administration and other domestic and foreign regulatory agencies, the initiation, timing and results of pending or future clinical trials, as well as risk factors listed from time to time in the company's reports as filed with the U.S. Securities and Exchange Commission, including but not limited to, its reports on Forms 10-Q and 10-K, may affect the actual results achieved by the company.
NOTE: Pharmacyclics(R), the "pentadentate" logo(R) and ANTRIN(TM) are trademarks of Pharmacyclics, Inc.
SOURCE Pharmacyclics, Inc.
/CONTACT: Leiv Lea of Pharmacyclics, Inc., 408-774-0330; or
Angela M. Bitting of Russell-Welsh, Inc., 650-312-0700, ext. 15, for
Pharmacyclics; or Mike Goodkind of Stanford University, 650-725-5376 or
650-723-6911/
/Company News On-Call: prnewswire.com or fax,
800-758-5804, ext. 110031/
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