Modern medicine has brought with it a large number of breakthrough scientific developments over the past decade, each of which has changed the way individuals in a range of patient populations receive care. Many of these breakthroughs have translated to considerable upside revaluations for the companies spearheading them. With this in mind, here are two companies that are on the edge of breakthrough developments in biotechnology and healthcare space, each of which could be about to (or might already have) change the face of the sector.
The two companies in focus are VBI Vaccines Inc (NASDAQ:VBIV) and Merck & Co., Inc. (NYSE:MRK).
VBI Vaccines (VBIV) is a US-based biotechnology company with a pipeline that spans a host of different indications, ranging from infectious diseases to oncology. The company’s lead asset is a hepatitis B vaccine called SciBVac, which is currently approved in 15 regions globally and about to embark on a multi-region phase III study designed to underpin an approval in the US, Europe and Canada. This asset isn't what qualifies it for this list, however.
Instead, the novel mechanism of action that earns VBI top spot on this list forms the basis of a drug designed to treat a condition called glioblastoma multiforme, or GBM, which is the most common form of brain cancer and is incredibly difficult to treat.
The current standard of care, SOC, therapy in this indication is surgical resection initially, followed by a traditional combination of chemotherapy and radiation treatment. With brain cancer, however, and especially as relates to GBM, the cancerous cells develop into a sort of tentacle-like formation that spreads deep into the brain. This makes surgical resection incredibly difficult and, in turn, limits the efficacy of the subsequent chemotherapy and radiation treatment.
So where does VBI come into the picture?
The company is developing a vaccine for a virus called cytomegalovirus, or CMV. The vaccine is a recombinant DNA type vaccine, built using VBI’s proprietary envelope Virus-Like Particle, or eVLP, platform, and employs a selection of antigens unique to the CMV virus to stimulate the production of CMV-specific antibodies in the patient receiving the drug.
Concurrent to this program, the company is also adapting the CMV-associated MOA to potentially target GBM based on a body of historical evidence that suggests a link between this form of brain cancer and the CMV viruses.
Specifically, evidence suggests that GBM cancer cells express an antigen that is also expressed by the CMV virus. Using this commonality, the company has created a vaccine that instructs the immune system to create antibodies specific to this expression. Once these antibodies are created, they circulate systemically looking for any cells that express an antigen normally associated with CMV, but also, in this instance associated with GBM. The circulating antibodies recognize the GBM cells as pathogenic – as if they were CM infected cells – and signals the rest of the immune system – T cells, macrophages, etc. – to attack and clean up.
What’s interesting about this one, then, is that VBI is using the traditional approach to prophylaxis vaccination and adapting it to form the basis of a cancer therapy. If the company can get this asset through the clinical development pathway and successfully past the FDA in the US, it will be the first time a company has used a crossover approach like this to underpin the MOA of a commercialized asset.
This is an early stage program right now, with the company focused primarily on advancing its registration trial for the above-noted hepatitis B asset from a resource allocation perspective. With that noted, a phase I study in this indication is underway and we should see some indication of progress – and potential clinical benefit – during 2018.
Next up is Merck (MRK).
Many reading will likely already be familiar with Merck’s blockbuster oncology asset, Keytruda. The drug, which first picked up approval in the US at the turn of the decade, has quickly expanded by way of various supplemental New Drug Applications (sNDAs) into a well established SOC in no small cell lung cancer, breast cancer, melanoma and more.
In terms of its impact on the oncology space, it’s proven a breakthrough therapy. During June, however, the FDA made a landmark decision that earns the drug not just the title of breakthrough, but potentially revolutionary in the cancer space, and by proxy, earns Merck and Keytruda a spot on this list.
Those familiar with the mechanics of oncology will likely already be familiar with the concept of tumour-specific genetic mutations. For those not yet familiar with this concept, the idea is that all cancers, whatever the type, are rooted in a specific genetic mutation. The genetic mutation results in a damaged DNA sequence that, in turn, results in faulty cell production. The production of damaged cells from faulty DNA (as caused by a genetic mutation at mRNA stage) translates to the unchecked proliferation we commonly associate with cancer, and which forms the basis of tumor growth in tissue.
Putting that concept aside for a moment, current SOC treatment in oncology is tissue specific. That is, a physician determines the best course of treatment for a patient based on the tissue in which the cancer resides – breast, pancreas, brain, bone etc. This is somewhat effective, but scientists have long theorized that a more accurate method of treatment allocation might be rooted in the specific genetic mutation that caused the cancer, as opposed to the tissue in which the cancer resides.
Breast cancer can be rooted in the same genetic mutation as lung cancer, for example, but as things stand, a physician will generally prescribe a different course of treatment for each. This is because, up until recently, no company has been able to come up with a drug that has demonstrated efficacy in patients with the same mutation-derived cancer, regardless of tissue type.
With Keytruda, Merck has done just that.
Well, it’s technically not Merck that has proved the concept. The company supplied a consortium of research entities (primarily consisting of Universities in the US) with Keytruda for the latter to conduct a study, and the NIH funded the investigation. The goal was to prove the above hypothesis. The trial investigated the efficacy of Keytruda as administered across a spate of different solid tumor cancers in – importantly – late stage patients. That is patients that have already undergone the SOC combination of chemotherapy and radio action as well as, in many cases, various courses of immunotherapy. In other words, these are patients that have no options available to them outside of a palliative care environment and – in many cases – have weeks or months at the outside to live.
The study enrolled a little over 80 patients based on a specific combination of mutations and gave them all a course of Keytruda. It didn't matter sort of cancer these patients had (so long as it is a solid tumor cancer), only that the cancer was rooted in one of the two specific mutations in question.
In June, the research consortium published the results in the online Journal of Oncology and the results were incredible.
Of the 86 patients enrolled in the study, 77% demonstrated stable disease, defined as tumor regression or tumor stability (i.e. The tumor got smaller or didn't grow any bigger). In 17% of the patients, the tumor disappeared altogether.
It’s difficult to get across how important these results are. Patients with this sort of advanced solid tumor cancer generally see stable disease rates in the single digit percentage bracket. One in ten lives more than five years. In the study outlined above, more than three out of every four patients saw their cancer stop advancing or recede. Just say of one in five were essentially cured – defined as cancer free at follow-up. Of course, cancer can return, but this far from negates the importance of this outcome.
In short, this study has shown that mutation-specific cancer treatment can stop cancer to a degree that no other type of therapy has been able to before, and can do so in very late stage patients across a spectrum of tissue type cancers.
This is a huge step forward in the oncology landscape, and the FDA agrees. In an unprecedented move, the agency in the US looked at the published data (remember, this data wasn't published by a company and the trial wasn't investigator-sponsored) and immediately approved Keytruda as a spectrum-wide cancer therapy for patients with the two specific mutations in question.
Expect this approval to bring with it a wave of development stage programs designed to build on the success of Keytruda and bring more mutation-specific oncology therapies to market over the next decade.