"Star Trek" Becomes Reality With These 3 Revolutionary Cancer-Fighting Methods

The next-generation of cancer-fighting agents could be right around the corner.

Jan 7, 2014 at 1:25PM

We may not be able to beam people from point A to B just yet as they did in Star Trek, but the pace of innovation within the biopharmaceutical sector is breathtaking at times. The evolution of hepatitis-C therapies over the past two-and-a-half years, for example, has changed the quality of life for patients in a dramatic way.

Prior to May 2011 when Vertex Pharmaceuticals' Incivek was approved, the standard treatment for patients infected with hepatitis C was 24 to 48 weeks of pegylated interferon in combination with a ribavirin. This treatment delivered about a 50% response rate (not a cure, merely some sort of measurable response), and most patients dealt with the nasty flu-like side effects of interferon for up to 48 weeks.

Following Incivek's approval, sustained virologic response (i.e., an undetectable level of disease) after 24 weeks jumped to 79%. Just two years and change later, the approval of Gilead Sciences' Sovaldi brings an FDA-approved drug to market that can deliver 90%-plus SVR in 12 weeks (or even eight weeks, based on its latest experimental phase 3 trial in combination with ledipasvir). Best of all, some genotypes no longer require interferon.

We could be on the precipice of that same great innovative leap with cancer therapies, and it all starts with three Star Trek-like innovative new cancer therapy approaches.

Stillassets
Source: Novartis.

Antibody-drug conjugates
In years past, there has been one primary way to attack cancer: as a global phenomenon. While chemotherapy solutions were developed to target specific types of cancer, there wasn't a way for this toxin to differentiate between healthy cells and cancer cells. In other words, the chemotherapy option was a war of attrition on a patient's entire body.

Then along came antibody-drug conjugates, or ADCs.

An ADC utilizes FDA-approved chemotherapy toxins, which are essentially piggybacked onto an antibody and targeted at cancer cells. What's truly unique about ADCs is that the toxin they carry isn't released until it comes into contact with a specific protein that only the target cancer cells will have. To put this another way, ADCs drastically eliminate healthy cell death and focus the brunt of the toxin delivery on the cancer itself.

There are currently three players within the ADC field: Seattle Genetics (NASDAQ:SGEN), ImmunoGen (NASDAQ:IMGN), and the relatively new entrant, Immunomedics (NASDAQ:IMMU).

Seattle Genetics' claim to fame is Adcetris, an FDA-approved ADC that targets the CD30 protein in Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL) patients. In the clinical studies that led to its approval, Adcetris delivered a 73% complete or partial response in HL patients and an even more impressive 86% complete or partial response for ALCL sufferers. 

Like Seattle Genetics, ImmunoGen, which refers to its ADC technology by its proprietary platform name "Targeted Antibody Payload," has one FDA-approved drug, Kadcyla. Kadcyla, which is used in combination with Roche's Herceptin, was approved to treat late-stage HER2-positive metastatic breast cancer last February after it improved progression-free survival by 50% and delivered a nearly six month improvement in median overall survival over the placebo. Don't forget as well that ImmunoGen is currently collaborating with seven prominent biopharmaceutical companies in addition to its own in-house cancer therapies.  

Finally, Immunomedics recently received patents on its SN-38 ADCs and hopes to report positive mid-stage results for IMMU-130 and IMMU-132 sometime in the first half of 2014.

Cancer immunotherapies
Instead of throwing targeted toxins into the body, the approach that Dendreon (NASDAQ:DNDN), Bristol-Myers Squibb (NYSE:BMY), Merck (NYSE:MRK), and Inovio Pharmaceuticals (NASDAQ:INO) have taken is to retrain the body's own immune system to fight the disease through immunotherapy vaccine options.

Perhaps the most well-known (and also disappointing) is Dendreon's Provenge for metastatic prostate cancer. The procedure involves collecting some of a patient's immune cells (leukapheresis), exposing them to a signature protein that stimulates them to attack prostate cancer cells, and then returning those immune cells back to the patient. This process is repeated a total of three times at two-week intervals as the full course of treatment. In trials, that bought patients an additional 4.1 months in median overall survival. Unfortunately, the launch of Provenge hasn't been managed well by Dendreon, leaving it on the backburner relative to competing metastatic prostate cancer drugs.

However, three experimental drugs could be waiting in the wings to offer the next chance for cancer immunotherapies to shine.

Antiemetic Injection

Source: Phil & Pam Gradwell, Flickr.

Both Bristol-Myers Squibb and Merck are developing anti-PD1 inhibitors, known as nivolumab for Bristol and lambrolizumab for Merck. The purpose of these two early stage therapies is to prevent a protein known as PD-1 from binding with PD-L1 and PD-L2. "Why is this important?" you wonder? Because this protein is suspected to be a big reason why cancer cells go undetected by our immune system. With this protein blocked, we can retrain our autoimmune system to recognize cancer cells as foreign and fight them.

With regard to Bristol's nivolumab, which is given in conjunction with FDA-approved therapy Yervoy, 53% of advanced melanoma patients responded in a phase 1 trial, with those who responded seeing at least 80% tumor shrinkage within 12 weeks. Merck's lambrolizumab, on the other hand, demonstrated a 52% overall response rate at its optimal dosage in an advanced melanoma trial.

Inovio, in addition to infectious disease vaccines, is developing an array of cancer vaccines in both clinical (cervical dysplasia, cervical cancer, and head and neck cancer) and preclinical (breast and lung cancer) settings. Inovio's most advanced study is its cervical dysplasia trial, which is midway through phase 2 studies and demonstrated, according to Inovio, "that the vaccine is capable not only of driving robust immune responses to antigens from high risk types of human papillomavirus (HPV) infection but that these immune responses displayed a powerful killing effect on cells changed by HPV into precancerous dysplasias." Inovio is certainly an intriguing name to watch in 2014 and beyond.

Anti-cancer stem cell therapeutics
If piggybacking a toxin onto an antibody or retraining your immune system isn't Star Trek enough for you, then perhaps OncoMed Pharmaceuticals' (NASDAQ:OMED) solution will hit the nail on the head.

OncoMed's experimental research goes far beyond just targeting cancer cells and aims to develop therapies that go after cancer stem cells, or CSCs. CSCs are extremely important because they're often immune to chemotherapy toxins and are essentially the origin of cancer cells. If OncoMed could develop a drug targeting these cancer cells, it could, in theory, stop the heart of cancer cell growth before it starts.

The idea may sound a bit like science fiction, but Celgene likes what it's seen so much that it recently entered into a multibillion-dollar potential collaboration with OncoMed that nets OncoMed $155 million in cash up front and a $22.25 million equity investment from Celgene into OncoMed's stock, and could net more than $2 billion in milestone payments if all six of its researched anti-CSC drugs live up to their full potential.

In an early stage (phase 1b) trial involving lead drug demcizumab in combination with pemetrexed and carboplatin, OncoMed notes that disease control (stable disease plus partial responses) was established in 94% of non-small cell lung cancer patients. It's early, but extremely encouraging news.

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Fool contributor Sean Williams has no material interest in any companies mentioned in this article. You can follow him on CAPS under the screen name TMFUltraLong, track every pick he makes under the screen name TrackUltraLong, and check him out on Twitter, where he goes by the handle @TMFUltraLong.

The Motley Fool recommends Celgene, Gilead Sciences, ImmunoGen, Seattle Genetics, and Vertex Pharmaceuticals. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.

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