BioHorizon » Gastrointestinal

Oncology Update: regorafenib improves survival in metastatic colorectal cancer (mCRC)

tim — Wed, 26 Oct 2011 17:27:01 +0000

According to a press release issued by Onyx Pharmaceuticals, Inc. on October 25, 2011 a Phase 3 trial with regorafenib in metastatic colorectal cancer (mCRC) patients being conducted by Bayer HealthCare Pharmaceuticals met its primary endpoint of improved overall survival. Apparently, this trial’s independent Data Monitoring Committee conducted a pre-planned interim analysis and recommended that the study be unblinded and patients in the placebo arm be offered treatment with regorafenib. While no data has been made publicly available at this time, given the positive nature of the announcement we have expedited our review of this multikinase inhibitor. We are currently reviewing the published pre-clinical and early stage clinical trial data, as well as mCRC clinical epidemiology to provide clients with analytical support for organization specific reimbursement and list/don’t list formulary decisions.

Abbott Labs ABT-874 for Treatment of Crohn’s Disease

admin — Thu, 11 Nov 2004 19:04:27 +0000

On November 11, 2004 the results of an Abbott Labs Phase 2 Crohn’s disease clinical trial examining the safety and efficacy of ABT-874 were published in the New England Journal of Medicine. , ABT-874 is a monoclonal antibody designed to target interleukin-12 (IL-12). The authors concluded that treatment with ABT-874 may have caused clinical responses and remissions in patients with active Crohn’s disease; however, at no time were the remission rates in the ABT-874 groups significantly different from those in the placebo group. Other significant findings of note include a decrease in Th1-mediated inflammatory cytokines at the site of disease. 79 eligible patients were enrolled in this study and these participants received either ABT-874 by injection or placebo across a range of dosages and frequencies. Emerging technologies entering Phase 2 are awarded a baseline 50 efficacy points; we have are adjusted this to 40 based on our analysis of the published results.

ABT–874 is a fully human, monoclonal antibody directed against an inflammatory cytokine known as IL-12. IL-12 is a known mediator of inflammation and may be important in Crohn’s disease. Given the inflammatory nature of Crohn’s, many targets related to immune system function are being pursued. Already, approved infliximab targets the tumor necrosis factor, another member of the class of inflammatory cytokines. We have assigned ABT-874 a score of 60 for innovation status.

Crohn’s disease is a chronic, inflammatory disease of the gastrointestinal tract that affects between 500,000 and 1 million Americans. Usually diagnosed before age 30, symptoms include diarrhea, cramping, abdominal pain, weight loss, fever, and in some cases rectal bleeding. There is no cure for Crohn’s disease. Incidence estimates for this disease vary greatly, ranging from 1/100, 000 cases per year to 70/100, 000. Published studies seem to cluster around the 5-10/100, 000 range resulting in a burden of illness score of 10.

We have scored the demand/diffusion variable at 10 resulting in an overall BioHorizon Emerging Health Technology Impact Score of 30, placing ABT-874 in our Low Impact Technology category. No preliminary assessment activities are required at present.

Technology Details
Target Disease / Indication: Crohn’s Disease
Technology Classification: Drug
Body System: Gastrointestinal
Program Area: Medicine/Gastroenterology
Regulatory Status: Phase 2
BioHorizon Impact Score: 30/100 – Low

Sanofi-Synthelabo’s Eloxatin for Postsurgical Treatment of Stage III Colon Cancer

admin — Fri, 05 Nov 2004 18:46:41 +0000

On November 5, 2004 Sanofi-Synthelabo’s Eloxatin™ (oxaliplatin for injection) received US FDA approval for use in combination with conventional chemotherapy (5-flurouracil and leukovorin) for the postsurgical treatment of stage III colon cancer patients. According to the company, this is the first new chemotherapy approval for the adjuvant treatment of colon cancer in over a decade. Approval for this new indication was based on the MOSAIC study, an international Phase 3 clinical trial enrolling over 2000 patients. According to the company there was a statistically significant improvement in the primary end point of disease free survival at a median follow-up of 4 years compared with infusional 5-FU/LV. The company concluded that these results demonstrated that the addition of Eloxatin to conventional adjuvant chemotherapy for colon cancer (5-FU/LV) reduced the risk of recurrence of cancer by 24% in the overall patient population who had undergone surgery to remove their primary tumor. Based on the FDA’s ruling, BioHorizon assigns a score of 100/100 to Eloxatin for efficacy.

Eloxatin was first approved in the US in January 2004 for the first-line treatment of advanced carcinoma of the colon or rectum in combination with infusional 5-FU/LV. In August 2002, this combination received approval for second-line treatment of this patient population (i.e., therapy for already treated patients with metastatic colorectal cancer). Oxaliplatin is a third-generation platinum derivative currently marketed by Sanofi-Aventis in more than 60 countries for the treatment of metastatic colorectal cancer. BioHorizon has assigned this emerging chemotherapy agent 65 points for innovation.

American Cancer Society estimates that 106,370 new cases of colon cancer will be diagnosed in the United States in 2004. This represents an incidence of 37/100,000 Americans and results in a burden of illness score of 18. Standard care for most colon cancer patients is surgical resection; however, a significant number of these patients will be candidates for adjuvant chemotherapy regimens designed to reduce the risk of the cancer’s recurrence and/or spread. Demand/diffusion will depend upon the extent to which oncologists integrate Eloxatin into adjuvant regimens. According to company news releases, global sales of Eloxatin rose 54.5 percent to 873 million euros ($1.1 billion) in the first nine months of 2004. Eloxatin earns a demand/diffusion score of 50.

Eloxatin receives a Moderate/High Score of 58. We are recommending commencement of assessment activities as soon as possible. Clients are advised to consult with key prescribing oncologists while reviewing the clinical epidemiology of colorectal
cancer.

Technology Details
Target Disease / Indication: Colorectal Cancer
Technology Classification: Drug
Body System: Gastrointestinal System
Program Area: Medicine/Oncology
Regulatory Status: Approved
BioHorizon Impact Score: 58/100 – Moderate/High

Lorus Therapeutics GTI-2040 for Colon Cancer

admin — Tue, 04 May 2004 20:49:44 +0000

On May 4, 2004 Lorus Therapeutics Inc. reported that it had initiated a clinical trial of GTI-2040 involving patients with advanced unresectable colon cancer. GTI-2040 was administered in combination with FDA approved chemotherapies capecitabine and oxaliplatin. Capectiabine is a first-line therapy while oxaliplatin is approved for use with 5 fluorouracil/ Leucovorin. This study is one of six clinical studies comprising the collaboration between Lorus and the U.S. National Cancer Institute’s Cancer Therapy Evaluation Program (CTEP). According to company releases, in pre-clinical studies GTI-2040 has successfully reduced the size of human adenocarcinoma tumors of the colon by 80% when injected into mice. Other pre-clinical findings include a broad spectrum of activity in vivo across many tumor types, and a 65% to 95% inhibition of lung metastases in two animal models.

GTI-2040 is a drug that exerts its activity by targeting a part of the ribonucleotide reductase enzyme known as R2. This enzyme is required for DNA synthesis and cell division. R2 is elevated in a wide variety of tumors and in some circumstances is thought to interact with cancer-causing genes to produce malignant cells with metastatic potential. Lorus states that the mechanisms of cytotoxicity of capecitabine and oxaliplatin, including inhibition of DNA repair, will be enhanced by this R2 blockade in colon cancer patients.

According to the American Cancer Society, an estimated 106,370 new cases of colon cancer and 56,730 deaths are expected to occur in 2004, making colon cancer the third most common cancer in the United States.

Biohorizon is currently monitoring the progress of 76 emerging technologies for the diagnosis and treatment of colon and colorectal cancer, including 48 drugs or diagnostic tests in Phase II or later stage of development. The recent approval of Avastin for metastatic colorectal cancer highlights the importance of keeping abreast of developments in this critical disease indication. The pivotal clinical trials necessary for FDA approval have yet to commence for GTI-2040 and therefore we currently are recommending no assessment activities for this promising technology.

Technology Details
Target Disease / Indication: Colon Cancer
Technology Classification: Drug
Body System: Gastrointestinal System
Program Area: Medicine/Oncology
Regulatory Status: Phase II
BioHorizon Impact Score: 38/100 – Moderate

Erbitux

admin — Fri, 13 Feb 2004 20:25:34 +0000

On Feb 12, 2004, ImClone Systems Incorporated and Bristol-Myers Squibb Company announced that the FDA approved the Erbitux (cetuximab) Injection for use in combination with irinotecan in the treatment of certain colorectal cancer patients. Particularly, Erbitux has been approved for patients with Epidermal Growth Factor Receptor (EGFR) expressing, metastatic colorectal cancer who are refractory to irinotecan-based chemotherapy and for use as a single agent in the treatment of patients with EGFR-expressing, metastatic colorectal cancer who are intolerant to irinotecan-based chemotherapy. Erbitux is a chimeric monoclonal antibody (MAb), which features a structure of approximately one-third mouse protein sequence and two-thirds human protein sequence, that binds to EGFR. Over expression of EGFR is common in a number of solid-tumor cancers, and Erbitux may block epidermal growth factor and transforming growth factor-alpha (TGF-alpha) from binding to this receptor, thereby potentially slowing tumor growth. ImClone has estimated that over 70% of advanced stage colorectal cancer cases express EGFR.

The American Cancer Society estimates that 147,500 new cases of colorectal cancer will be diagnosed in the United States in 2003. This makes colorectal cancer the third most commonly diagnosed cancer and the second leading cause of cancer death in the United States.

The FDA submission included data from a randomized two-arm Phase II clinical study conducted by Merck KGaA which evaluated Erbitux as a single agent and the combination of Erbitux and irinotecan in 329 patients with EGFR-expressing metastatic colorectal cancer who were refractory to irinotecan-based chemotherapy. The findings showed that Erbitux given in combination with irinotecan (n=218) had an objective response rate of 22.9 percent, a median duration of response of 5.7 months and a median time to disease progression of 4.1 months. Results of the Erbitux single agent study (n=57) showed a 9 percent objective response rate and a median duration of response of 4.2 months.

Our research indicates that Wall Street analysts are forecasting a wide range of possible gross sales numbers for Erbitux ranging from 200 million to 1.5 billion dollars per year. Most analysts are using the 15,000 to 20,000 dollar per patient per treatment assumption in their models.

Erbitux represents the first EGFR blocker/inhibitor to receive regulatory approval and represents true innovation. We have designated Erbitux as a High Impact emerging health technology and recommend preliminary assessment activities.

Technology Details
Target Disease / Indication: Metastatic Colon Cancer
Technology Classification: Drug – Chimeric Monoclonal Antibody (EGFR inhibitor)
Body System: Gastrointestinal System
Program Area: Medicine/Oncology
Regulatory Status: Approved
BioHorizon Impact Score: 68/100 – High

Avastin

admin — Fri, 06 Feb 2004 14:00:56 +0000

In early December 2003, Genentech announced that the Biologics License Application (BLA) for Avastin (bevacizumab) as a first line therapy in metastatic colorectal cancer had been submitted to the FDA. Genentech requested and received a ‘Priority Review’ designation. Priority Review status means that the FDA will take action on the BLA within six months of receipt of the document, which in Avastin’s case is by the end of March, 2004. Avastin inhibits the function of a protein called Vascular Endothelial Growth Factor (VEGF). Simply put, tumor cells require blood to survive, just like any normal cell in the body. VEGF plays a vital role in the ability of tumor cells to grow new blood vessels, a process called angiogenesis. In theory, inhibiting VEGF with Avastin should interfere with a tumor’s blood supply and prevent growth or spread.

The American Cancer Society estimates that 147 500 new cases of colorectal cancer will be diagnosed in the United States in 2003. This makes colorectal cancer the third most commonly diagnosed cancer and the second leading cause of cancer death in the United States.

According to Genentech, more than 2,000 patients have been treated with Avastin in clinical studies. The current BLA filing is based upon the results of a pivotal 900 patient study of Avastin plus the three other chemotherapy agents comprising the IFL regimen (5-FU/Leucovorin/CPT-11). Genentech reported that Avastin plus the IFL regimen improved median survival by approximately five months, compared to patients treated with chemotherapy alone (20.3 months versus 15.6 months).

Wall Street analysts position Avastin in the 1billion dollar/year sales range. The actual cost per patient treated is not known at this time but new cancer therapies typically cost somewhere in the $12 000 – $20 000 per patient per year range. It is critical to note that these costs will be in addition to the costs of treating metastatic colon cancer with existing chemotherapy regimens as, initially, Avastin will likely be used in addition to the IFL chemotherapy regimen.

If approved, we feel that Genentech’s Avastin has the potential to be a High Impact technology and therefore we recommend oncology programs begin some early assessment activities while watching for the FDA’s decision. Early steps would include the identification of current and predicted metastatic colon cancer patient numbers and some discussion with treating oncologists concerning future plans for Avastin in treatment regimens.

Technology Details
Target Disease / Indication: First Line Therapy in Metastatic Colorectal Cancer
Technology Classification: Drug
Body System: Gastrointestinal System
Program Area: Medicine/Oncology
Regulatory Status: Biologics License Application Submitted to FDA
BioHorizon Impact Score: 70/100 – High