|Pluristem's Unique Therapy Primed to Replace Blockbuster Drugs for Treating Peripheral Arterial Disease|
Press Release: Equity Briefing – 1 hour 3 minutes ago
A close examination of emerging biotech Pluristem Therapeutics ( PSTI), whose unique cell therapy is being applied to a number of clinical disorders, shows promise.
Peripheral arterial disease (PAD), under-diagnosed and, in some cases, over-treated, is one of the fastest-growing conditions to affect an aging population. 10 million Americans have PAD today and the number is expected to rise to 23 million by 2014. Its presence signals circulatory problems that play into medicine`s largest industries - heart disease and stroke. We believe the market is ready for a new treatment, cell therapy, with lower overall cost, quicker healing time, no toxicity, and ease of administration - a simple intramuscular injection - to help improve the PAD sufferers` way of life.
Several big pharmas sell drugs for PAD including Bristol-Myers Sqibb Co. ( BMY) and Sanofi ( SNY) which sell Plavix; Teva Pharmaceuticals ( TEVA) sells Pletal; AstraZeneca ( AZN) sells Atacand; Bristol-Myers also sells Avapro; and Merck & Co. ( MRK) sell Cozaar/Hyzaar. Combined sales for these drugs are well over $12 billion. Each of the drugs has side effects and they do not cure PAD. As an alternative, or in addition to drugs, cevices such as stents are surgeries are costly, risky, and not consistently effective.
Pluristem`s PLX cells offer a new paradigm to treat PAD by growing new vessels - offering a potential cure, not just a way to manage the disease.
Peripheral arterial disease (PAD), , is a vascular disease affecting the legs. Its cause is atherosclerosis, where blood flow within arteries becomes restricted from blood-borne debris, allowing plaque to form that narrows and hardens the vessel wall. The first indication of PAD is walking pain, known as intermittent claudication (IC). Left untreated, blood flow to the legs is further limited, resulting in critical leg ischemia (CLI), or dying arterial tissue; almost half of PAD patients with IC progress to CLI. At this point, ulcers and gangrene may develop with amputation as the only option.
Two goals are targeted when treating PAD: managing leg pain and halting the progression of atherosclerosis, which, when present, may be a signal that its appearance is elsewhere in the body, raising the risk of heart attack and stroke. Often doctors suggest combining medicine for PAD with procedural intervention. In severe cases, vascular surgery is recommended.
Pharmaceutical treatment for PAD falls in two major categories - drugs that improve blood flow and those that thin blood to avoid excessive clotting that intensifies atherosclerosis. Aspirin, coumadin, and heparin have been standards of care as anti-clotting agents that inhibit platelets, small cell fragments that circulate in blood, from forming clots.
Then came clopidogrel, or Plavix, made and sold by Bristol-Myers Sqibb Co. ( BMY) and Sanofi ( SNY). It works by inhibiting a receptor on platelet cell membranes so they become less `sticky` and clots are less likely to form. The drug quickly rose to blockbuster status and is today the second most prescribed pharmaceutical in the U.S., next to anti-cholesterol agent Lipitor, marketed by Pfizer, Inc. ( PFE). Sales of Plavix were $7.1 billion in 2011, up 6% over the prior year, and accounted for 33% of Bristol-Myers` net revenue. Treatment with Plavix is lifelong.
Bestseller Plavix`s Surprising Drug Interactions and Alarming Side Effects
But there are problems with Plavix. Two years ago, the FDA put a `black box` warning on the popular drug, citing a lack of efficacy in an astounding 14% of patients. It was discovered that people with certain genetic characteristics simply cannot metabolize the drug, rendering it useless in the body. Sadly, the patient would need to take Plavix over time before it is determined that it doesn`t work, setting up a scenario of further arterial blockage. The only solution is a genetic test given either before or after administration of the drug - at price of $500 - and a wait time of two weeks.
Side effects of Plavix are not insignificant. There is minor and major bleeding that occurs in up to 5% of users; life threatening bleeding can happen in over 2%. In some cases, a condition known as thrombotic thrombocytopenic purpura, or TTP, may present itself, where blood clots actually form in small vessels throughout the body, reversing any benefit of the drug.
What`s worse, physicians from the University of Maryland Medical Center have shown that Lipitor can reduce the effectiveness of Plavix, which is an interesting medical twist because sufferers of PAD are many times prescribed a cholesterol-lowering drug to slow its progression. Certain popular antibiotics also reduce Plavix` effectiveness. Gastro-intestinal drugs Nexium and Prilosec, made by AstraZeneca plc ( AZN) and Proctor & Gamble Co. ( PG), respectively, inhibit a key enzyme that activates Plavix. Additionally, the widespread anti-depressant Prozac, sold by Eli Lilly & Co. ( LLY), is known to lessen the drug`s value.
One independent study this year went as far as to show that Levitra, marketed by GlaxoSmithKline plc ( GSK), used in conjunction with Plavix hindered the effect of the erectile dysfunction medicine in half the study`s subjects.
PAD`s Other Costly Treatments Comprise Large Markets - with Drawbacks
Additional drugs to treat PAD target improving blood flow and reducing hypertension; both comprise large pharmaceutical markets. Cilostazol, or Pletal, sold as a generic by Teva Pharmaceuticals ( TEVA), has sales upwards of $200 million, according to drug database giant IMS Health. The only compound specifically labeled for IC, Pletal counts headache and diarrhea as its common side effects and improvements in walking may take up to 12 weeks to appear. Unfortunately, Pletal is contraindicated in patients with heart disease, severely limiting its use in PAD where the condition is many times a forerunner of cardiac artery clogging.
High blood pressure medications represent a huge worldwide market. Three of the most prescribed - Atacand made by AstraZeneca, Avapro, by Bristol-Myers, and Cozaar/Hyzaar, by Merck & Co. ( MRK) have combined sales of $12 billion. Like anti-platelets, these must be taken throughout the patient`s lifetime and the most common side effect of dizziness must be endured.
One of the largest studies describing the high cost of PAD treatment was published in the Journal of Managed Care Pharmacya number of years ago. Over 30,000 subjects with an average age of 70 years showed that 67% had hypertension; 57% had high cholesterol; 47% had ischemic heart disease; and 55% had heart failure. In the general population, a meta-analysis showed that these conditions led to one-half the death rate of people with PAD 50 years and older.
Hospitalization is a key cost in PAD care - an incredible 75% of a patient`s total expense, much higher than the typical rate of 36% for other illnesses. Since PAD is an indicator of a disease process within the entire circulatory system, it is not surprising that leading reasons for hospitalization were respiratory-, cardiovascular-, or cerebrovascular-related. It is also known that one-third of PAD patients visit the hospital within two years of diagnosis.
In the article, it was cited that drugs to treat PAD accounted for over 10% of patient-related expenses, considering claims for office and outpatient visits, lab tests, emergency department visits, and medical procedures. It was concluded that by the end of the first year after diagnosis with PAD, the health care resource burden is comparable with a diagnosis of myocardial infarction.
Don`t Count on Devices or Surgery as a Helpful Alternative to PAD Drugs
In more serious cases, angioplasty or surgery may be necessary to treat PAD. As in coronary angioplasty, drug-coated stents are often the device of choice as they have shown, in hearts, to reduce restenosis rates (arterial re-clogging). For PAD, however, results are not as striking.
In June, 2011, Chan, et.al published in the International Journal of Clinical Practice evidence that the Cypher stent, made by Cordis Endovascular, a Johnson & Johnson ( JNJ) company was safe and effective in preventing restenosis after peripheral angioplasty. The problem, however, becomes one of cost, particularly since re-stenting may be necessary within as short as six months as the polymer with which the stent is constructed has been shown to cause further clotting. Four additional studies are ongoing.
Vascular surgery, by far the most invasive method of treating PAD, involves an expensive diagnostic - Doppler ultrasound - and a hospital stay that, along with the bypass graft procedure, can run as high as $45,000. Afterwards, extensive physical rehabilitation is necessary; healing time can be up to three months. A greater number of complications arise from this type of open surgery. According to Fisher, et.al in a recent issue of Podiatry Today, the procedure has been shown to require revisions in almost 50% of patients within six months.
Enter Pluristem`s PLX Solution
We view Pluristem`s PLX technology, showing positive results in clinical trials, as a highly favorable alternative to a life of side-effect producing medication, the hope of less-invasive catheter procedures that may or may not be effective, and the dread of debilitating surgery. In Phase I/II studies in 27 patients with CLI, the company demonstrated an 85% amputation-free survival rate within three months of treatment and improved blood flow with less pain. There was no evidence of an immune response and no significant adverse side effects. A pivotal study is planned for the first quarter of 2013.
Because vessel regrowth is a prominent feature of PLX-processed cells, ischemic disease will be a featured clinical goal. Last March, Pluristem unveiled results of a preclinical trial in mice whose major cardiac artery was severed to mimic heart attack. Within four weeks, treated animals showed vastly improved heart function with a significant reduction in the amount of dead heart tissue. More studies are being designed.
About The Analyst: Sharon Di Stefano
Sharon di Stefano has spent 20 years as a healthcare analyst, beginning her career at Smith Barney, Harris Upham & Co. specializing in medical devices, pharmaceuticals, healthcare information technology, and biopharmacology. Ms. di Stefano had also served as Senior Venture Officer for the Edison Innovation Fund, implemented through the New Jersey Economic Development Authority that provided funding for early-stage life sciences companies. Industry experience includes laboratory research for Johns Hopkins Hospital and the Department of Defense.