Peripheral artery disease or PAD is a silent killer.
Amazingly, despite all the options available in the US, amputation rates run as high as 40% in CLI (critical leg ischemia) patients in the first year following their diagnosis, with mortality rates approaching 20%.
It is estimated that 160,000 amputations due to PAD are performed each year in the U.S.
The market is clearly ready for new treatments.
PAD develops when arteries in the legs become clogged with plaque (fatty deposits) that limit blood flow. Just like clogged arteries in the heart, clogged arteries in the legs raise the risk for heart attack or stroke. PAD affects 8 to 12 million people in the United States, especially those over age 50.
The Sage group estimates that a 25% reduction in the number of amputations could save $29 billion in US health care costs.
The first symptom of PAD is walking pain, known as intermittent claudication (IC). If PAD is 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.
The blockages in peripheral arteries are of greater length and spread out over a larger area than in coronary arteries.
Recurrence is frequent.
Repeat hospitalizations and related expenses increase the overall price tag of treatment. Treating PAD is estimated to cost about 6 % more than treating Coronary Artery Disease. Additionally, diabetics have more extensive PAD than non-diabetics.
Treatment options presently available for PAD include drugs, surgery, lasers, and drills, which make it possible to open up clogged arteries and hardened plague-ridden arterial walls.
Several medications, such as anti-lipid, anti-platelet, and anti-hypertensive medications, can help prevent the onset of PAD or alleviate symptoms. None address the substance of the illness.
The drug has been a blockbuster for many years. Sales of Plavix were $7.1 billion in 2011, and $1.5 billion in the first half of 2012.
Sales dropped after Plavix lost its patent protection in May 2012 and the FDA approved generic versions of it.
Generic versions run about a $1 a day at Walmart and other chain stores as opposed to brand-name Plavix at $6.44 per day.
AstraZeneca (AZN)'s Brilinta, reduces the risk of heart attacks, strokes and death. It was approved in 2011 for use in patients with severe chest pain or a history of heart attacks.
In the new Euclid trial, Brilinta is being tested on patients with peripheral artery disease in an attempt to gain approval for that indication and to differentiate it from Plavix.
This next idea may speak to the substance of the condition.
AngesMG Inc, a Japanese company, is developing Collategene, a gene therapy that uses HGF ((Hepatocyte Growth Factor)).
HGF is known to have strong angiogenic (promoting new blood vessels) activity. HGF Plasmid is a regenerative medicine that, when placed at the right location near the ischemia, helps produce new blood vessels.
A virus (a so-called virus vector) is not used to carry the genetic material, thus the problems generally associated with viral vectors do not arise.
With the help of Mitsubishi Tanabe Pharma, the company is preparing a phase 3 trial aimed at the US market.
The treatment starts with taking a small volume (~60mL) of bone marrow aspiration (soft tissue in liquid form from the bone marrow) from the patient. It is sent to the lab where the cells are expanded for about 12 days. The material is then returned to the clinic where it is injected into the patient's leg.
Pluristem (PSTI) is an Israeli company that extracts stem cells from placentas, not embryos, thus avoiding ethical issues.
In small phase 1 and 2 studies of 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.
Angioplasty is used alongside drug treatment, or when drugs don't work.
As in coronary angioplasty, drug-coated stents are the device of choice as they have been shown to reduce arterial re-clogging.
For PAD, however, they do not seem to work as successfully. Re-stenting is often necessary, sometimes within a short period of time.
Stent migration and in-stent stenosis are feared complications. The polymer used in stents has been found to cause further clotting.
The IN.PACT Admiral Drug-Eluting Balloon delivers a novel formulation of paclitaxel into the cell lining of the blood vessel. Therefore, instead of being swept into the general circulation, paclitaxel remains in the vessel wall for around seven days, averting cell proliferation as an immediate response to the treatment, but not preventing healing in the longer term.
In this treatment no stent is left behind.
Medtronic collaborated with two German scientists: cardiologist Dr Bruno Scheller from the University of Saarland and Professor Ulrich Speck of the Charite Hospital, Berlin.
Central to this project was a novel formulation of paclitaxel, called FreePac, which uses the organic chemical urea as an intermediary to keep molecules of paclitaxel apart.
This allows the drug to be evenly coated on the surface of the balloon, thus precisely controlling the dose, which is applied in 30-60 seconds.
This method of treatment will be groundbreaking, if it works.
The phase 2 trial will test it on several hundred patients at up to 55 U.S. sites.
Another promising procedure for improving CLI outcomes is stenting the below-the-knee arteries with the Xpert stent, manufactured by Abbott (ABT).
Among patients treated with the Xpert stent, 78% were alive without any amputation at 12 months.
The device was evaluated in 120 CLI patients with below-the-knee lesions of 4-15 cm in length. A total of 140 limbs and 212 implanted devices were included in the study.
Zilver PTX is a paclitaxel-eluting stent from Cook Medical, a privately held company.
The femoropopliteal segment (the section of the leg above the knee) is particularly challenging to treat because it is subject to substantial external forces, including bending, twisting, and contraction.
The Zilver PTX multicenter trial compared a paclitaxel-coated, self-expanding nitinol stent with PTA (angioplasty only, no stents) in lesions up to 14 cm long above the knee.
The one-year results have been so promising that an FDA advisory panel unanimously recommended approval of the Zilver PTX in October 2011. Zilver PTX is already approved in Australia, Japan, and Europe.
Nitinol has a unique feature: shape memory. The alloy can undergo deformation at one temperature, then recover its original, undeformed shape when heated above its "transformation temperature."
This feature of nitinol makes it a good choice for use in stents.
A collapsed stent can be inserted into a vein and heated, thereby returning to its original expanded shape, helping to improve blood flow.
When the blockage is too tough for balloons and stents, drills may be tried.
Boston Scientific (BSX) has a new one: TruePath CTO Device. Boston Scientific inherited this when it acquired ReVascular Therapeutics in 2011.
CTO stands for chronic total occlusions.
CTOs are complete artery blockages and are extremely difficult to treat with standard endovascular devices such as guidewires.
The TruePath Device features a rotating diamond-coated tip designed to break through blocked peripheral arteries and facilitate the placement of conventional guidewires for treatment.
The ultra-low 0.018" profile is roughly half the size of competitive devices. Once positioned, the tip rotates at 13,000 rpm to facilitate drilling through calcified lesions.
The device is approved in the US and Europe.
The investor's take:
Peripheral vascular devices, including stents, angioplasty balloons, and synthetic grafts, generated $4.3 billion in global revenue in 2010 and may earn $5.6 billion in 2014, according to Technavio, a market research firm in Elmhurst, Illinois.
This is a huge market that so far has not been served very well. Most of the star drugs like Plavix and Lipitor are generic now, and Crestor will be soon. There is plenty of room for new drugs and procedures.