Affecting more than 65,000 new patients and claiming about 11,000 lives annually, melanoma treatment represents a huge unmet need. With the knowledge that sun exposure is responsible for the cause of about two-thirds of all melanoma cases, May has been dubbed "melanoma awareness month" dedicated to the education of skin cancer and sun exposure awareness. Like many diseases, prevention is most important in fighting this disease with common-sense approaches such as reducing exposure to sunlight and wearing sunscreen, sunglasses, hats and other sun-protective clothing to cover your body. Early detection is most important in skin cancers and melanoma as well as other cancers. A lifestyle of excessive exposure to the sun or a genetic predisposition means a more diligent approach is necessary to early detection via self inspection and more frequent visits to your physician particularly if any changes occur in size or coloration of any blemishes, warts or moles.
Regardless of many prevention measures, many will continue developing melanoma. Certain careers and hobbies involving continuous exposure to the sun and genetic predispositions will remain and the disease must still be treated. Although only representing 4-5 percent of all skin cancer diagnoses, melanoma is deadliest and causes most skin cancer deaths. Innovative pharmaceutical companies have been taking varied approaches in attacking melanoma with varying degrees of success in their pipelines and fighting the disease at multiple levels of development. Following are some novel treatments currently in clinical trials to fight melanoma and offer real hope to the patients and physicians fighting the cancer on its front lines.
GlaxoSmithKline (NYSE:GSK) announced on May 17th that its Phase II trial for a combination of dabrafenib, designed to work in patients with a mutation of a gene known as BRAF, and trametinib, which interferes with a protein known as MEK is showing early promise. The drug combination data from the 77 patient trial helped patients live for a median of 7.4 months before their disease progressed. Within the 77 patient group, 24 patients received a dosage that researchers view as optimal and is now being developed in more advanced trials. Patients of this subset experienced progression free survival of 10.8 months. Subset determinations are necessary and are part of the clinical development protocol in trials as optimal dosages, optimal administration techniques and optimal timing are all necessary along with determining the optimal patient set to be treated. To be considered is its market potential with about half of all melanomas having the BRAF aberration, a huge patient set. Roche Holdings' (OTCQX:RHHBY) vemurafenib, is the only BRAF inhibitor currently approved for treating melanoma. However, about 1/3 of patients taking the drug develop a less deadly cutaneous squamous cell carcinoma and many patients eventually develop a resistance to the drug. If the GSK combination set continues on with the current success rate and safety profile, they could be taking market share from vemurafenib in the near future.
The most novel approach from the least-known company of the set, OncoSec Medical, Inc (NASDAQ:ONCS) utilizes a process called electroporation. Part of their OMS ElectroImmunotherapy treatment regimen, electroporation is the process of applying a brief electrical current to a tumor which causes a more than 1,000-fold increase in its permeability. Previously injected Interleukin-12 (IL-12) rapidly permeates the outer membrane of the tumor and is sealed in the tumor once the current is removed. Interleukins are a group of molecules involved in the growth, development and maintenance of several immunity system cells and responses. IL-12 is normally produced by dendritic, or antigen-presenting cells (APC's) and has strong anti-cancer activity. In the body, IL-12 activates cytotoxic lymphocytes which effectively attack the tumor. However, the compound is very toxic and its administration must be carefully regulated. OncoSec's OMS ElectroImmunotherapy treatment greatly reduces the systemic exposure to IL-12 and instead utilizes it to target specific tumors.
On February 28th OncoSec announced dosing of its first patient in a Phase II trial for metastatic melanoma. A total of 25 patients will be treated in this single-arm, open-label and multi-center trial. OncoSec hopes the trial will validate the safety and efficacy seen in its Phase I trial in which the procedure was determined to be safe and well tolerated. In this trial, 53% of patients with distant metastatic lesions had an objective response with 15% of these having a complete response. Take note, these responses are based on the overall prognoses of the patients, not just the responses in a few lesions. This differentiation should be kept in mind as investors perform their research in the clinical data in order to keep an "apples to apples" comparison.
Provectus Pharmaceuticals, Inc. (NYSEMKT:PVCT) is using a novel approach of selective solubility to target cancer cells. Their PV-10 melanoma has completed Phase II clinicals, and the company is planning a Phase III trial. PV-10 is comprised of a 10% solution of Rose Bengal disodium which has a 30-minute half-life (the amount of time it takes for half of the compound to degrade or breakdown) and is excreted through the bile. The compound only has minutes to achieve its goal of permeating cancer cells before it degrades. Its selectively is due to the nonpolar or fat soluble nature of Rose Bengal. Cancer cells have a much higher lipid content in their membranes than normal cells do. In studies of the solubilities of chemicals, polar compounds dissolve in polar compounds and nonpolar compounds dissolve in nonpolar compounds (nonpolar PV-10 dissolving in and therefore permeating through the lipid-containing cancer cell outer membranes). Once inside the cancer cells, autolysis occurs in 30-60 minutes, a process in which lysomes found in the cells' themselves burst, releasing digestive enzymes destroying the cell from the inside out.
The so-called "bystander affect", as it's called by the company, may aid in PV-10's efficacy. When the affected cancer cells undergo autolysis, their contents are exposed to APC's. The contents contain antigenic tumor fragments and the APC's create an immune response against not only these tumor fragments but possibly other tumors found in the patient with similar expressions. In a sense, the immune system "learns" what the cancer cells look like through the fragments and then attacks the other intact cancer cells found nearby. Phase II results appeared to be positive with 24 percent of the patients having complete response (CR) in target lesions while 25 percent having partial responses (PR) for a total overall response rate of 49 percent. Looking at the bystander effect, CR of the untreated lesions was reported at 24 percent with PR of 13 percent for an overall of 37 percent. No grade 4 or 5 adverse events were attributed to the treatment regimen. While having local efficacy on lesions, the data comparisons for Provectus' and OncoSec's two therapies are not direct comparisons. For example, the complete response data sets vary dramatically. OncoSec's ElectroImmunotherapy regimen boasted a 15 percent complete response rate for the disease as a whole while PV-10 had a 24 percent complete response rate for only the targeted lesions. In order for biotech investors to make a decision on efficacy comparisons, the data set needs to be broken down for Provectus to determine how the patients responded as a whole in terms of complete response rate. The author would like to see a more head-to-head comparison made via the PV-10 Phase II data presentation. Perhaps that unveiling could be coming soon as the plans for the Phase III trial progress.
Amgen, Inc. (NASDAQ:AMGN) acquired privately-held BioVex Group in March of 2011 for up to $1 billion with $425 million down as cash and the rest in milestone payments due to its advancing and solid pipeline. At the time of the acquisition, BioVex's OncoVex (GM-CSF) was deep into a Phase III trial for patients for advanced melanoma. OncoVex has dual mechanisms to aid in its efficacy. Based on an oncolytic herpes virus with GM-CSF (a macrophage colony stimulating factor agent) encoding, the agent is injected into the melanoma lesions where the virus enters the cancer cells only causing an oncolytic effect in the injected tumor (cancer cells are infected with the virus and subsequently self-destruct). The cell fragments are then taken up by APC's and the localized GM-CSF expression causes an immune-mediated anti-tumor effect on the non-injected tumors. Phase III trial data is expected in the near future, and success there could represent considerable income for Amgen and significant milestone payments to its wholly-owned BioVex division. Phase II data were impressive with 20 percent of patients ultimately achieving a CR. In a comparable fashion, OncoSec's Phase I melanoma trial had a 15 percent CR and the Phase II trial underway for it should hopefully validate the efficacy in the coming months.
These companies each represent very unique and novel methods to fighting melanoma. OncoSec's ElectroImmunotherapy Phase I results indicate good efficacy and a good safety profile. The Phase II trial now underway could validate the approach and could be a real headliner in the coming months with solid efficacy reported. A direct comparison to Provectus's PV-10 is difficult and potential investors are advised to make certain the comparisons they make are true head-to-head comparisons. Amgen/BioVex's OncoVex (GM-CSF) therapy has shown very promising data to date with a huge catalyst coming in this year's Phase III results for advanced melanoma. Success there may legitimize the therapy's approach for other cancers as well, such as the same drug for head and neck cancer also currently in Phase III clinicals. OncoSec's approximate $9.0 million market capitalization would be extremely undervalued if Phase II efficacy is even only marginal considering its growing pipeline strength. When comparing the therapy's mechanism to OncoVex (GM-CSF), OncoSec's IL-12 production is known to produce GM-CSF in the immune cascade while the reverse cannot be said as GM-CSF does not produce IL-12. Whether or not there is enough additional efficacy imparted by this "side production" remains to be seen but certainly should only help. Amgen was willing to pay up to $1 billion for BioVex, however it was deep into its Phase III trial at the time of acquisition. Prorating this back to early Phase II pricing would be speculative and highly subjective but likely much more than the current $9 million market cap for OncoSec. GlaxoSmithKline is a true powerhouse in the pharmaceutical world and appears to be developing yet another promising therapy in its dabrafenib/trametinib combination. If it keeps its safety profile in check, the company could be well on its way to another successful trial. Investors, individual and institutional, as well as potential suitors will likely be watching very closely in the coming months. As the overall markets continue to degrade, investors looking for pharmaceuticals with near-term catalysts for capital appreciation should certainly review the potential in OncoSec, GlaxoSmithKline, Provectus and Amgen with varying levels of risk at varying stages of development.