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This article originally featured in Baillie Gifford’s Autumn 2019 issue of Trust magazine.
When Svetlana Viteva first encountered Novocure’s cancer-fighting Optune device, her initial reaction was one of disbelief: “It looked like this crazy electric helmet that someone was wearing, and they said: ‘It has the potential to cure brain cancer.’ You think, right, okay, that sounds insane.”
But although the idea of using electric fields to kill cancer may sound like science fiction, her investment antenna began to tingle when she saw the clinical data. Viteva’s mission is to find young, immature companies with the potential to become the big winners of tomorrow: Novocure had just published the interim results of a trial suggesting that by combining electric fields with conventional chemotherapy drugs, it could extend the lives of patients with an extremely aggressive form of brain cancer by around five months.
Together with a growing number of oncologists, Viteva believes this new approach could transform the treatment of brain cancers, and many others besides. And for now at least, Novocure is the only company exploiting it.
Novocure was founded in 2000, and is the brainchild of an Israeli biophysicist called Professor Yoram Palti. He had spent much of his career investigating the use of electric fields to detect and treat abnormal heart rhythms – but began to wonder if they might also be used to interfere with cancer cell division.
Optune, a wearable electric field generator © Novacure 2019. All Rights reserved.
All living cells contain electrically charged molecules and structures, which are involved in essential processes, including cell division. When a cell begins to divide, charged proteins are released, which facilitate this. “The laws of physics tell you that if there is a charged particle and you surround it with an electric field, there will be a force exerted on that particle,” says Viteva. “Palti’s starting hypothesis was that this, in theory, should be able to stop cell division, particularly in [rapidly-dividing] cancer cells.”
Indeed, Palti demonstrated that alternating electric fields could disrupt and kill cancer cells in all 17 cancer cell types he tested – although the precise frequency varied. Crucially, the frequencies that killed cancer cells left healthy cells unscathed.
In 2003, Novocure conducted its first test on human subjects. The results suggested that these so-called tumour-treating fields (TTFields) were safe to use in cancer patients; the following year, it launched a clinical trial in patients with the brain cancer glioblastoma.
Novocure’s decision to go after glioblastoma was a strategic one: it is the commonest form of brain cancer, and the deadliest. There are 12,500 new cases each year in the US alone, and there is no cure. Median survival for patients undergoing standard treatment – surgery, radiation therapy and chemotherapy – is just 16 months. If Novocure could prove that TTFields were effective in this population, it should be easier to convince people of its efficacy in other types of solid tumour.
The device they came up with was Optune, a wearable electric field generator, connected to a battery and four ‘transducer arrays’, which stick to the patient’s shaved head and deliver low-frequency alternating electric fields to their tumour. “It’s very compact, and probably lighter than most people’s laptops, so you can walk around with it and go about your daily life without being tethered to a bed or a hospital,” says Viteva.
She stresses that the device is not intended to be a replacement for conventional therapy – rather, it is complementary to it: “The fact that it wasn’t an extra drug really appealed to me. Because it is not a drug, you don’t feel it at all – the only reported side effect has been skin irritation.”
© Novacure 2019. All Rights reserved.
Convincing oncologists has been more difficult: “Doctors took a very long time to get on board and I can’t even say that today everyone is on board,” says Viteva. A key turning point was the publication of the five-year survival data. With standard care, just five per cent of glioblastoma patients will still be alive five years after diagnosis; when TTFields were combined with this approach, it was 13 per cent.
However, for the most compliant patients, the news was better still. The electric fields emitting from the Optune device only inhibit cancer cell division when it is switched on. Novocure recommends wearing it for 75 per cent of the time (roughly 18 hours a day), but some patients have it switched on day and night. For those wearing it 90 per cent of the time or more, the five-year survival rate was 29 per cent.
Yet, exciting as all this is, Viteva believes it is just the tip of the iceberg. The only constraint for this type of therapy is your ability to surround the tumour with an electric field, Viteva points out. You can’t really do that with blood cancers, but you can with solid tumours – and these account for 90 per cent of all cancers, including four of the most common: breast, lung, colon and prostate cancer. “The opportunity is massive,” she says.
Novocure Clinical Pipeline
In May 2019, the Food and Drug Administration (FDA) in the US approved the use of TTFields in combination with chemotherapy for mesothelioma, a cancer which often affects the lungs, and is commonly associated with asbestos exposure – the first new FDA-approved mesothelioma treatment for more than 15 years. Novocure is also currently exploring its use in brain metastases, non-small cell lung cancer, ovarian and advanced pancreatic cancer.
The company owns all commercialisation rights to the use of TTFields in oncology and has foundational patent protection until 2031 in the US, and 2026 elsewhere.
It has also patented the use of TTFields as combination therapies. “Even when the patents expire, a competitor would have to show that they are superior to Optune, and it would be quite hard for them to catch up,” says Viteva.
Challenges remain, however. One is tailoring the frequencies to individual patients: “There are nuances between older and younger people and that is something they are experimenting with now,” Viteva explains. The data also suggest that TTFields are more effective at higher intensities, but ramping up the intensity causes heating, which could be dangerous. Perhaps the biggest challenge of all is one common to all existing cancer therapies: tumours’ ability to mutate and develop resistance. “At the moment, we don’t have real-time imaging instrumentation to observe how tumours change as electrical fields are applied to them,” says Viteva. “These cells will evolve and continue to mutate, and their electrical properties will change as you surround them with that field.”
Cancer remains a formidable and shape-shifting enemy, but the emergence of TTFields provides a radically different weapon to any that has existed before. For cancer patients, it brings a fresh spark of hope.
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Linda is an author, journalist and broadcaster, covering biomedical sciences and technology. She regularly contributes to Nature and The Guardian, and is a consultant to New Scientist.