Seeking Alpha December 6, 2012 - Pancreatic Cancer
Pancreatic cancer incidence is increasing worldwide with almost 220,000 cases per year, and there is a significant need for effective therapies.
Advanced pancreatic cancer is fourth most common cause of cancer death in the United States and the world. The one-year relative survival rate is 26% and the five-year survival rate is only about 6%. If the cancer is detected at an early stage and can be removed surgically, the five-year survival rate is about 22%. Since pancreatic cancer patients seldom exhibit disease-specific symptoms until later stages, more than 85% of patients with pancreatic cancer are diagnosed at advanced tumor stages leaving them without any surgical therapy options. The treatment options for pancreatic cancer are limited and generally ineffective.
The American Cancer Society estimates that:
About 43,920 people (22,090 men and 21,830 women) in the United States will be diagnosed with pancreatic cancer in 2012.
About 37,390 people (18,850 men and 18,540 women) in the United States will die of pancreatic cancer in 2012.
Since 2004, rates of pancreatic cancer have increased about 1.5% per year. The lifetime risk of developing pancreatic cancer is about 1 in 71 (1.41%). The risk is about the same for men and women.
According to Transparency Market Research, the global pancreatic cancer drug market is projected to reach $1.2 billion by 2015. The research firm found that Eli Lilly's (LLY) Gemzar (gemcitabine) has an approximate 55% share of the market. Genentech/Roche (RHHBY.OB) and Astellas/OSI Pharmaceuticals (ALPMY.PK) Tarceva (erlotinib) have captured the whole of the market since these are the only U.S. Food and Drug Administration (FDA) approved therapies available.
According to GlobalData, the pancreatic cancer market is forecast to exhibit a 4.1% negative compound annual growth rate (CAGR) between 2009 and 2016. This revenue decrease is primarily due to the estimated patent expiry of Eli Lilly's Gemzar (gemcitabine) and Roche/Genentech's Xeloda (capecitabine). Although new products that are currently in Phase 3 trials could enter the market soon, it will take some time for physicians to use new products rather than Gemzar. While Lilly's Gemzar patent will expire and generics will influence market revenue, GlobalData believes there will be no substantial improvement in the unmet need. Newer entrants might exhibit promising results but they have yet to prove their efficacy. Global Data predicts that the overall pancreatic cancer market, which showed growth between 2001 and 2009, will experience a decline in revenue between 2009 and 2014.
In 2011, the FDA approved Pfifer's (PFE) Sutent (sunitinib malate) and Novartis' (NVS) Afinitor (everolimus) for the treatment of unresectable pancreatic neuroendocrine tumors, a rare type of pancreatic cancer. Patients with advanced pancreatic neuroendocrine tumors (pNET) have few treatment options. Prior to these approvals, no new drug was approved by the FDA in three decades.
This year, several pharmaceutical companies announced good news about the progress of their investigational pancreatic drugs:
In June 2012, Momenta Pharmaceuticals (MNTA), announced that preclinical data showed that M402 in combination with gemcitabine prolonged survival and substantially lowered the incidence of metastasis in two pancreatic cancer models.
In June, Edward J. Kim, MD, PhD, of the University of Michigan, announced results from a small study that found one-half of all patients with advanced pancreatic cancer had objective responses or stable disease when they received vismodegib (GDC-449, Erivedge) and gemcitabine. The data was reported at the American Association for Cancer Research Pancreatic Cancer Conference in Lake Tahoe, Nevada. Vismodegib is being developed by Roche/Genentech, under a collaboration agreement between Curis (CRIS) and Genentech. Vismodegib targets smoothened protein, a key mediator of hedgehog signaling. The drug recently received FDA approval for treatment of basal cell carcinoma.
In July, the Journal of Clinical Oncology published the results of a Phase 2 study that found patients with locally advanced or metastatic pancreatic neuroendocrine tumors (NETs) appear to benefit from the combination of temozolomide [Merck's (MRK) Temodar, generics] and bevacizumab (Roche/Genentech's Avastin). The study found response rates to be 33% among those with NETs compared with no response among patients with carcinoid tumors, consistent with prior studies.
In November 2012, Oncolytics Biotech (ONCY) announced two poster presentations covering expanded results from a Phase 2 clinical trial using intravenous administration of REOLYSIN (Respiratory Enteric Orphan Virus) with gemcitabine. in patients with advanced pancreatic cancer (REO 017), as well as preclinical research in Ras-activated pancreatic cancer. The study found that 33 of a planned 36 patients had received Reovirus (REOLYSIN) (3 x 1010 TCID50) intravenously daily on days one to five, in combination with carboplatin and paclitaxel. Molecular tumor demographics included: 16 Kras, three EGFR, four BRAF mutations, and 10 EGFR amplified only. Response evaluation to date among 30 evaluable patients showed 27 patients had stable disease or better for a 90% clinical benefit rate [nine partial response (PR) (30%) and 18 stable disease (SD) (60%)]. Three patients had progressive disease (PD) as their best response.
The best news came on November 9, 2012. Celgene (CELG) said a late-stage study comprised of 861 patients found that a combination of the company's drug, Abraxane (paclitaxel protein-bound) and gemcitabine was more effective than gemcitabine alone in treating pancreatic cancer. Abraxane has been approved by the FDA to treat breast and lung cancer. Celgene will apply for approval to market the drug to treat pancreatic cancer. Celgene acquired Abraxane with the acquisition of Abraxis BioScience in 2010 for $2.9 billion. The drug combines the cancer chemotherapy paclitaxel with the protein, albumin, which Celgene contends helps deliver a greater amount of chemotherapy to cancer cells with fewer side effects. The company expects to release detailed data from the trial in January 2013 and plans to file an application with the FDA to market the drug to treat pancreatic cancer.
Cancer Gene Therapy Week -- Oncolytics Biotech Inc. ("Oncolytics") announced three poster presentations covering expanded results from: a Phase II clinical trial using intravenous administration of REOLYSIN in combination with paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC) with Kras or EGFR-activated tumours (REO 016), a Phase II clinical trial using intravenous administration of REOLYSIN( )in combination with gemcitabine (Gemzar(®)) in patients with advanced pancreatic cancer (REO 017), as well as preclinical research in Ras-activated pancreatic cancer. The presentations are being made at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics being held in Dublin, Ireland from November 6(th) through 9(th), 2012 (see also Oncolytics Biotech Inc.).
"We continue to expand our library of positive clinical data in a variety of indications like lung and pancreatic cancers," said Dr. Brad Thompson, President and CEO of Oncolytics. "Positive results from these earlier studies have further validated our decisions to advance both these indications into randomized Phase II testing."
The poster presentation titled "Phase II Trial of Oncolytic Reovirus in Combination with Chemotherapy in NSCLC Pts with Kras Activated Tumors" covers the latest results from the REO 016 study.
Thirty-three of a planned 36 patients had received Reovirus (REOLYSIN) intravenously daily on days one to five, in combination with carboplatin and paclitaxel. Molecular tumor demographics included: 16 Kras, three EGFR, four BRAF mutations, and 10 EGFR amplified only. Response evaluation to date among 30 evaluable patients showed 27 patients had stable disease or better for a 90% clinical benefit rate (nine partial response (PR) (30%) and 18 stable disease (SD) (60%)). Three patients had progressive disease (PD) as their best response.
The poster presentation titled "A study of REOLYSIN in Combination with Gemcitabine in Patients with Advanced Pancreatic Adenocarcinoma" covers updated results from the REO 017 study. The trial is a 33-patient study using a one sample, two-stage design. In the first stage, 17 patients were to be enrolled, and best response noted. If three or more responses were observed (defined as complete response (CR), PR or SD for 12 weeks or more) among the 17 patients, the study would enroll an additional 16 patients for a total of 33 evaluable patients. As previously disclosed, this initial endpoint was met after six evaluable patients were enrolled and the study continued to enroll the total of 33 patients. The treatment was well tolerated. Response evaluation to date among 25 evaluable patients showed 20 patients had stable disease or better (one PR, one unconfirmed PR, 6 SD at six weeks, and 12 SD at 12 or more weeks). Five patients had PD as their best response. A number of patients remain on study with some too early in their treatments to evaluate.
The poster presentation titled "Reovirus Therapy Induces Endoplasmic Reticular (ER) Stress and Apoptosis in RAS-Activated Pancreatic Cancer" discusses findings from preclinical research conducted using REOLYSIN.
The researchers demonstrated that cells with activated RAS are under intrinsically higher levels of ER stress and that reovirus infection leads to enhanced ER stress and apoptosis in mutant RAS pancreatic cancer cells. Further induction of ER stress with bortezomib increases the efficacy of REOLYSIN against pancreatic cancer cells.