Glioblastoma multiforme is a byword for intractability: patients with the disease survive for barely a year on average after diagnosis. With the survival advantage of each new approved drug or technology measured almost in hours, the market – not to mention patients – would warmly welcome a therapy that made a real difference.
The German firm MagForce believes it is has that therapy. “We have a unique technology,” Hoda Tawfik, the company’s co-chief executive, tells EP Vantage, and unique it is: NanoTherm therapy, already approved in Europe, involves the use of magnetic nanoparticles to sensitise a tumour to other treatments or even to burn it away entirely.
NanoTherm therapy involves direct injection of nanoparticles, suspended in a fluid, into the tumour. “[These] are superparamagnetic iron oxide nanoparticles with a coating which causes the magnetic fluid to agglomerate shortly after injection,” Ms Tawfik says. “They stay where they are injected, almost like a sort of implant. Between 20% and 30% of the tumour has to be covered by the nanoparticles.”
Another step is required for the therapy to take effect. A couple of days after the nanoparticles are injected the patient lies in a machine that MagForce calls a NanoActivator, similar in appearance to an MRI scanner. “The patient enters the NanoActivator and an alternating magnetic field is applied at a very high frequency – the pole of the magnetic field changes over one hundred thousand times per second,” Ms Tawfik says. This causes the nanoparticles to oscillate and heat up, she explains.
Depending on the magnetic field applied, the particles, which are around 15nm in diameter, can be heated to around 40-45C, which can sensitise the tumour cells to chemotherapy or radiotherapy, or to a much higher temperature, causing tumour ablation.
The particles do not have to be removed from the patient afterwards, meaning that should the cancer recur – even years later – the patient can simply re-enter the NanoActivator and the process can be repeated.
But this leads to one of the technology’s drawbacks; because the particles interfere with magnetic fields, patients cannot undergo MRI scans. They would not be at risk, Ms Tawfik points out, but the magnetic field causes artefacts on the scans. MagForce consequently recommends that patients be monitored using CT or PET imaging.
The results of clinical trials of the technology have been better than what has so far been achieved with drugs. In a single-arm trial in 59 patients with recurrent glioblastoma use of NanoTherm in combination with radiotherapy extended median overall survival from diagnosis of the first tumour recurrence by 13.4 months. Median overall survival after primary tumour diagnosis was 23.2 months.
The best drug currently approved for glioblastoma, Merck & Co’s Temodar, can muster a 10-week improvement in overall survival when added to radiotherapy (Therapeutic Focus – Avastin provides glimmer in glioblastoma but progress still slow, August 17, 2012). A phase III trial of Roche’s all-purpose antibody Avastin is due to report overall survival data later this year, but otherwise pharma does not have much to offer.
The trial data are apparently sufficiently impressive to have convinced European authorities, and the technology was CE-marked in late 2010. MagForce is now starting a postmarketing trial, an open-label, randomised, controlled study testing NanoTherm as a monotherapy and in combination with radiotherapy versus radiotherapy alone in 280 glioblastoma patients.
Not surprisingly, the study is being conducted with one eye on the US. “We are planning to use this postmarketing study in case we need additional data for the FDA,” Ms Tawfik says. “We are planning to seek a pre-PMA meeting with the FDA, to get their advice and potentially adapt our postmarketing study to requirements of the FDA. Our aim is definitely to go on to the US market.”
The company does not have huge experience of the commercial side of things so far. The technology is currently only on sale in Germany, despite Europe-wide marketing authorisation. But it is exhibiting a certain nous with pricing, having come up with several ways for potential customers to pay.
“For the 10ml nanoparticle vial, which is more than enough to treat a tumour, the market price is €20,000,” Ms Tawfik says. “The [price of the] activator can be discussed with each clinic depending on whether they buy or lease it. If we have the activator in a hospital for a clinical trial, but they use it commercially, they can pay per use. We would put the price for that at €3,000 per use per patient.”
MagForce has ambitions beyond glioblastoma, and is conducting phase I trials of the technology in prostate and pancreatic cancers. But the next indication of whether NanoTherm will become the new hope for glioblastoma patients will be the FDA’s responses to MagForce’s overtures, and that in turn depends on the findings of the postmarketing trial.
Says Ms Tawfik: “What we want to do is to get regulatory approval in the US. Whatever the FDA needs from us, we will plan to do it.”