Until just recently, immunotherapy (or stimulation of the immune system to treat disease) was regarded as an ill-conceived approach in cancer drug development. Many scientists and investors did not consider immunotherapy treatment to be a legitimate area of cancer research. The skepticism was not totally unfounded as there had been years of failures, such as those from CancerVax, IDM, and Cell Genesys to name a few. However, the immunotherapy sector learned from previous mistakes and is now beginning to prevail. In April 2010, the FDA approved the first cancer immunotherapy, Dendreon's (DNDN) Provenge for prostate cancer. It then approved Bristol-Myers Squibb's (BMY) Yervoy for melanoma in March of the following year. Immunotherapy has emerged as a validated approach in the treatment of cancer, resulting in significant survival benefits with a superior safety profile to chemotherapy and radiation treatment. At the American Society of Clinical Oncology (OTC:ASCO) conference in early June, there were over 300 abstracts relating to immunotherapy. The technology's advancement is evident by its growth from that of less than 125 abstracts in 2009. This article highlights some of advancements in cancer immunotherapy that were presented at ASCO 2012.
According to Semantelli, a market research firm that tracks social media in the drug world, Bristol-Myers Squibb generated the third largest amount of buzz at ASCO this year with its cancer immunotherapy, BMS-936558. The anti-PD-1 antibody was shown to significantly reduce tumors in certain patients with melanoma, kidney, and lung cancers. Nine patients suffered from serious side effects, with three deaths resulting from lung inflammation. However, the safety profile did appear to be milder than that of Yervoy, which has already obtained marketing approval. What attracted so much attention was that previous treatment with conventional therapies was unsuccessful in these patients, so this was a difficult to treat patient set. BMS-936558 belongs to the same class of immunomodulators as Yervoy. Both antibodies target proteins (PD-1 and CTLA-4, respectively) that are found on and regulate the activity of cytotoxic T-lymphocytes, a type of immune cell that can kill foreign cells in the body. Cytotoxic T-cells are like blood hounds that can hunt down and kill tumors. Cancer cells have been shown to escape the body's immune system by suppressing the activity of cytotoxic T-cells via these two proteins. While BMS-936558 is relatively early in development, investment analysts are already forecasting peak sales of $2 billion for the drug.
Another immunotherapy that created some buzz was ImmunoCellular Therapeutics' (IMUC) ICT-107, a dendritic cell-based immunotherapy treating a very deadly form of brain cancer known as glioblastoma multiforme (GBM). If cytotoxic T-cells are like blood hounds, dendritic cells provide the scent by presenting the antigen (protein found on the surface of the cancer cells) the T-cells target. An update of survival rates from a Phase I study showed that eight of sixteen glioma patients treated with ICT-107 continued to survive for more than four years - six patients without any progression of disease. Three patients continue to survive beyond the five mark. Despite being a small, uncontrolled study, the survival rates are unprecedented considering that GBM patients on average survive less than two years. ICT-107 differentiates itself from many other immunotherapies in that it goes after multiple targets, including those associated with cancer stem cells (CSCs). CSCs have been shown to be resistant to conventional cancer therapies (i.e. radiation and chemotherapy) and are often responsible for tumor recurrence. Results from the Phase I study showed that ICT-107 was able to reduce the number of tumor cells expressing CD133, a molecular marker for CSCs. The company has currently enrolled over 200 patients for a randomized, placebo-controlled, multicenter, Phase II study and anticipates an interim analysis at the end of the year with final results near the end of 2013. Analysts anticipate peak sales of ICT-107 would be over $500 million once obtaining marketing approval for newly diagnosed GBM alone. However, with its multi-antigen approach in fighting cancer, ICT-107's GMB success could be the first of many as the multiple antigens targeted are found on many types of cancer.
Amgen (AMGN) presented updated Phase II results for blinatumomab (AMG103), which was recently obtained from the acquisition of Micromet at the beginning of the year. 72% (26 of 36) patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL) treated with AMG103 were able to achieve either a complete remission or CR with partial hematological recovery. Typically, fewer than 30% of similar patients achieve a CR with currently available therapies. The most common adverse events were mild (i.e. grade 1 or 2), including pyrexia, headache, tremor, and fatigue. However, there were a few more adverse events, such as seizures, encephalopathy, and cytokine release syndrome. Blinatumomab belongs to a new class of antibodies known as bi-specific T-cell engagers (BiTEs). The antibody binds to both CD19 and CD3; CD19 is found on B-cells, while CD3 is expressed on T-cells. Blinatumomab works by bringing T-cells in contact with and inducing T-cell killing of malignant B-cells. Amgen is currently enrolling a larger global Phase II study to evaluate AMG103 in B-precursor ALL patients with minimal residual disease. Interim results should be available near the end of 2012.
Data from this year's ASCO meeting certainly show how exciting the field of immunotherapy has become. Several cancer immunotherapy trial results, including GlaxoSmithKline's (GSK) MAGE-A3 lung cancer vaccine and Amgen's oncolytic virus TVEC for melanoma, are expected later this year or early next year. Any additional positive results and approvals should further solidify the broader value of cancer immunotherapies. Since 'a rising tide lifts all boats,' investors should be aware of the potential upside for companies with solid clinical-stage cancer immunotherapies in development. The upside could prove to be substantial for companies proving through clinicals that they have solid and legitimate pipelines, and the $132 million ImmunoCellular Therapeutics should be on the forefront of this increased investor attention. The previous negative opinions about the immunotherapy approach in fighting cancer have been proven false by Provenge and Yervoy approvals; while ICT-107 and other promising drugs in development may be leading the way for the next wave of approvals and hope for cancer patients. It will be interesting to see both the quality and quantity of immunotherapy agents presented at ASCO 2013 and beyond.