Brain tumors are among the most difficult to treat cancers in the oncology space. Their tendency for late stage diagnosis, and the difficulty associated with surgical treatment, translates to a higher than 65% mortality rate in the US, defined as the percentage of patients that die within five years of diagnosis. Choosing to pursue brain cancer treatment is risky for a company precisely because it is so hard to treat. That’s why new approaches are being pursued mainly by smaller companies trying to make an impact with bigger risk-taking. Here are four candidates from these smaller firms to keep in eye in 2016.
ImmunoCellular Therapeutics, Ltd. (NYSE:IMUC)
Immunotherapy has dominated the oncology space in 2015, and ImmunoCelllar’s candidate, ICT-107, uses a patient’s own dendritic cells to elicit an immune response. Tumor cells suppress the standard immune response by being unrecognizable to the body. Dendritic cells play a key role in our immune system’s recognizing harmful cells, by highlighting these cells for attack by other immune cells. By removing a small part of a patient’s tumor, ImmunoCellular can ex-vivo produce dendritic cells that specifically express the cancerous cell markers, and in doing so, produce a targeted attack response.
A phase II partially backed up the hypothesis, and in recently released updated top line data, ImmunoCellular reported a boost in overall survival of 10% in glioblastoma patients over placebo. While this sounds decent, the difference in the Kaplan-Meier survival curves for the two arms was still not statistically significant. The company still hopes though that the planned phase III trial can use data from the phase II to target more appropriate patients and get better results.
How? The drug performed even better in a specific subset of patients that are HLA-A2 positive – just meaning they express an antigen called HLA-A2. In its phase III registrational trial which is now recruiting patients, the company is only targeting this subset of patients, which by design could improve ICT-107’s chances of phase III success.
The phase II was still generally considered a failure by shareholders, which while discouraging, does put shares at a significant discount and means that if ImmunoCellular is able to hone the patient population for its phase III enough to show better results, shares could jump back to where they were in 2013 before initial phase II results were published. While chances are not particularly high, it does give ImmunoCellular a lot more upside than competitors if it can pull it off.
The other negative is that the company doesn’t expect data before December 2019 and won’t complete the study before December 2021
Del Mar Pharmaceuticals Inc. (OTCMKTS:DMPI)
DelMar is developing its lead candidate VAL-083 in a range of oncology indications, with its lead being a phase II expansion study in the treatment of glioblastoma multiforme – an aggressive and invasive type of brain tumor, with an incidence rate of around 22,000 annually in the US. The drug is what’s called an alkylating agent. Alkylating agents attach an alkyl group to DNA, and in doing so, inhibits the rapid proliferation associated with cancer cells. These sorts of treatments are already widely used in various forms of chemotherapy, but they have one serious drawback – they are not selective to tumor cells. This means they can damage healthy cells, in particular those that mirror the rapid proliferation of cancer cells.
In contrast, and as supported by studies conducted by the National Cancer Institute (NCI) and backed up by Del Mar’s own trials, VAL-083 seems to be selective in targeting tumor cells alone. Studies also suggest that not only does the drug perform well in patients resistant to current standard of care chemotherapy, but it also has a higher potency. With the improved safety profile that the selectivity provides, this means the drug could quickly become standard of care over the current Temodar on approval.
A recent phase II update built on the already available evidence, and Del Mar hopes to kick off a registrational trial during the first half of 2016. The trial will enroll 100 GBM patients, and the company is targeting an NDA submission date of mid to late 2017. Based on these timeframes, we could be looking at commercialization as soon as Q2 2018.
Vascular Biogenics Ltd. (NASDAQ:VBLT)
This Israel-based biotech is working on the development of its lead candidate, VB-111, targeting a host of solid tumor cancers. The most advanced of its trials, and the reasoning behind its inclusion on this list, is its phase III in recurrent GBM, which the company initiated in August. The study is enrolling, and Vascular expects to enroll 252 patients across the US, Canada and Israel, with the goal of comparing VB-111 in combination with Avastin, versus Avastin alone.
VB-111’s mechanism of action is rooted in the targeted destruction of the blood vessels that feed tumor cells. The company has developed PPE-1-3X, which is called a promoter that targets the cells that line angiogenic blood cells. Angiogenesis is the process through which new blood vessels form from old ones. The drug uses a viral vector to deliver the PPE-1-3X promoter to the desired location, in this instance the brain tumor.
Phase II data that compared the Avastin/VB-111 combination with historic Avastin data from four pooled trials suggested a two-fold increase in overall survival, and forms the basis of the phase III initiation. From a catalyst perspective, we are looking for any extended data from the already completed phase II (follow up studies, primarily), as well as interim data from the ongoing phase III. Vascular expects to report the latter of these two catalysts during the first quarter of 2017, and estimates primary completion by December the same year.
Burzynski Research Institute, Inc. (OTCMKTS:BZYR)
Burzynski is a controversial pick. The Burzynski Clinic is a Texas-based research institute, set up in the 1970’s by Polish immigrant Stanislaw Burzynski. It offers one kind of treatment, what the company refers to as antineoplaston therapy under the guise of clinical trials. Antineoplaton’s are not an approved treatment, and the company charges patients for access to the trials.
Over the last three decades, debate over the legality of this type of setup has raged across the oncology space. All the current indications are in phase II, meaning efficacy remains in question, yet under the current FDA regulatory framework, Burzynski is able to sell antineoplaston’s as cancer treatment. So why mention the company here? One of the biggest complaints surrounding Burzynski and his practices is his tendency to release vague, inconclusive statements surrounding trial data – see here for an example in a liver cancer indication.
On December 7 though the company bucked this trend and published somewhat more detailed figures from a phase II in an anaplastic astrocytoma indication. The study suggests some level of efficacy, with a median overall survival of 24.5 months. This at least puts antineoplaston therapy in line with current standard of care which is chemo and radiotherapy. With patients paying for treatment, the trial was not blinded, however, and only had one arm. No control was established. This makes it difficult to draw any real conclusions.
Having said this, the company has outlined communication with the FDA that suggests the regulatory agency will give its blessing for further development. Whether this means we will finally see a Burzynski-sponsored phase III, or simply a continuation of the phase II, remains unclear. As mentioned, a controversial inclusion but one that, if it succeeds, could change the way clinical trials are conducted in the United States by setting a precedent of allowing patients to pay for trials they want to participate in.