Some like it hot

The world’s big pharmaceutical companies are already under pressure from generic competition and the demise of blockbuster drugs. If that wasn’t bad enough, a new category of therapeutic interventions is becoming established, able to cure problems which were, up until now, continuously treated using drugs.

Fixing asthma — bronchial thermoplasty

Most people are familiar with inhalers for managing asthma. We’ve developed a few here at Team. Every day millions of people take asthma drugs to reduce the constriction of airways which causes shortness of breath and wheezing. Nobody is 100% certain why the airways in the lung are surrounded by a tube of muscle which can contract and cause this constriction. What is certain is that muscle constriction can be a big problem for asthmatics, in some cases even fatal.

In the late 1990s scientists began to explore the seemingly crazy idea of heating the bronchioles (the tubes which carry air into the lung) to ‘cook’ the smooth muscle in the airways and stop it constricting.

For many years, researchers have been exploring ways to treat severe asthma and in the late 1990s scientists began to explore the seemingly crazy idea of heating the bronchioles (the tubes which carry air into the lung) to ‘cook’ the smooth muscle in the airways and stop it constricting. The idea sounds painful and dangerous but research showed that heating the bronchioles to ~65°C would permanently damage the smooth muscle but not destroy the delicate lining.

It was a scary step to take the procedure into humans as, after all, the intention was to cause permanent damage to the patient’s lungs. There were two main concerns. Firstly, could the heat treatment be applied without causing collateral damage and trauma to the airways of an asthma patient who already had difficulty breathing? Secondly, would any long term deleterious effect occur if someone’s airways were no longer able to constrict?

The first human trial was cunningly done on a group of eight patients who were scheduled to have a chunk of lung (a lobe) removed because it was potentially cancerous. The treatment was carried out via a bronchoscope (a camera on a thin tube) pushed down into the lung. A small balloon catheter, with four external wires, was extended into the bronchiole and inflated. Once the wires were pushed against the inside wall of the bronchiole, a 10 second electrical pulse of RF (or radio frequency) energy was delivered, heating the surrounding tissue.

The airways leading to the suspect lobe were heat treated several weeks before the lobe was surgically removed and results showed that bronchial thermoplasty could be safely tolerated. In addition, when the bronchial tissue was examined under the microscope the scientists could see that the amount of smooth muscle was significantly reduced.

Almost a decade has passed and this technique is gradually becoming adopted more widely. The emerging body of evidence seems fairly compelling, and shows that there is some benefit in doing bronchial thermoplasty, although it isn’t an immediate or complete cure.

We now have data gathered from patients up to six years after treatment. Some proper clinical trials have been undertaken and the procedure is beginning to be approved and adopted. There remains a lack of evidence about the long term implications, hence the clinical community remains understandably cautious.

The whole procedure only takes about 30 minutes and the damage to the lining is barely visible and is repaired within a few weeks. The therapy is normally applied in three separate sessions with a gap of about a month between each session to allow the damaged tissue time to recover.

The results are extremely impressive and appear to be permanent with patients experiencing a reduction in symptoms and in medication. There is a small but non-trivial risk that long term problems may appear, say after 20-30 years, but as yet no such problems have been identified.

At present, bronchial thermoplasty is only being used on the most severe asthma patients who don’t respond to drug therapy. Adoption will probably increase beyond this group but it is unlikely that thermoplasty will ever be used to treat all asthmatics. The impact on sales of asthma drugs is currently small, but as the procedure gains adoption it could have a measureable impact.

Fixing high blood pressure — Renal denervation

High blood pressure is a huge health problem, and a significant contributor to the heart, lung and kidney diseases which consume such a vast amount of healthcare resources. Whilst diet, lifestyle and drugs all play a part in managing blood pressure, there are patients whose blood pressure can’t be controlled.

Blood pressure is regulated by the autonomic nervous system – the bit you and I (thankfully) don’t have to think about. Nerves which connect the brain to the heart and to the kidneys play a key role in regulating blood pressure.

In the first half of the 20th century, scientists investigated whether disrupting the autonomic nervous system would affect blood pressure, and found that by cutting the nerves running to and from the kidneys high blood pressure could be reduced. Unfortunately, as the nerves supplying the kidneys run alongside the large renal artery which delivers blood to the kidney, the only way of cutting the nerves was to cut the renal artery and then re-join it again, thereby severing the nerves (which didn’t regrow and reconnect).

Fast-forward half a century and the discipline of interventional radiology is now well established, with large blood vessels routinely used to gain access to a range of organs so they can be diagnosed and fixed. In the late 1990s, researchers began to investigate whether the renal nerves could be inactivated from inside the renal artery, and as a result developed the RF energy delivery catheter and balloon system, very similar to the bronchial thermoplasty system. The catheter is inserted via the femoral artery up into the renal artery, the balloon is inflated and delivers heat from inside the artery to damage the nerves running along the outside.

The medical device industry is highly excited at the prospect of a new therapeutic device to treat high blood pressure. In 2010, Medtronic paid $800 million to acquire Ardian, the pioneers of this renal denervation technique. Since then, most of the major medical device players have acquired companies or technology in renal denervation, and venture funding is flowing into new companies developing the procedure.

In the long term, this treatment will definitely have a significant impact on sales of blood pressure monitoring drugs. Some pharma companies are already making significant investment in potential new therapeutic device technologies. This seems a prudent move – while finding new blockbuster drugs is getting ever more difficult, the world of interventional medical devices seems ripe for innovation.