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Physicians' Financial News focuses on news-making and/or notable companies in the oncology/biotech sector. In this issue: 1) Bristol-Myers Squibb: BMS Boasts Bright Oncology Future 2) Infinity Pharmaceuticals and AstraZeneca: Prostate Cancer Partnership Begins to Bear Fruit 3) Genentech: Avastin Shown To Halt Brain Cancer Progress, and more
%u25BA BMS Boasts Bright Oncology Future
Bristol-Myers Squibb (BMS) is one of the world’s largest pharmaceutical companies. The product of a 1989 merger between Bristol-Myers and Squibb, both of the original concerns that comprise the conglomerate have a long and storied history.
Bristol-Myers was officially incorporated on December 13, 1887, with William Bristol as president and John Myers as vice president after the two partners had decided to invest $5,000 into a failing drug manufacturing firm called the Clinton Pharmaceutical Company. Squibb was created in 1858, launched as a family concern.
As BMS grew over time, the company evolved into a large and diversified worldwide concern. Currently, BMS has an employee roster of over 43,000 people and combined annual product sales that approach $18 billion. In addition to becoming a perennial major player in prescription pharmaceuticals, BMS has successfully branched out into related fields, establishing and leveraging subsidiary companies such as Mead Johnson Nutritionals, responsible for various popular consumer products (manufacturing, for example, the ubiquitous baby formula branded as Enfamil); ConvaTec, a leader in the ostomy care and wound therapeutics sectors; and Bristol-Myers Squibb Medical Imaging.
Recent History Marked by Hurdles
Throughout the 1990s, fortunes of the company soared on the strength of blockbuster products such as Pravachol, a cardiovascular agent; Glucophage, an oral therapy indicated for type 2 diabetes; and Plavix, an antiplatelet agent.
It was also during this time period that BMS gained increasing renown throughout the oncology sector, largely on the strength of Taxol, an ovarian, breast, bone (Kaposi’s Sarcoma), and lung cancer treatment agent touted on the company’s website as “one of the world’s most widely used cancer treatments.”
The early 2000s were a bit of a rocky period for BMS. Company personnel endured lay-offs and share prices of BMS stock fell sharply as several of its highest selling drugs lost patent protection and few new agents emerged from the BMS pipeline to take their place. The company also had to contend with new sources of competition and marketshare encroachment resulting from the dramatic growth and innovation of the biotechnology industry. Just before 2001, the per-share price of BMS stock was approaching $75 per share. A little over a year later, by early 2002, it had fallen in value to less than $30 per share.
Over the past several years, however, the traditional pharmaceutical house has surprised many analysts with its flexibility and responsiveness to the rapidly changing landscape of the pharmaceutical marketplace. As the drug market has undergone seismic changes and shifts, BMS has reinvented itself, transforming its tactical focus via a series of strategic acquisitions, collaborations, and a re-emphasis on research and development.
Wall Street has taken notice to the extent that BMS’s stock price has stabilized. The equity spent 2007 fluctuating between $26 and $32 per share. In fact, from mid-to-late summer in 2007, the stock rose to exceed $32 per share, a price it maintained or nearly maintained for several weeks. The summer 2007 peak represented the highest that BMS stock had climbed in over 5 ½ years. (At the time this article went to press, BMS stock was hovering at just under $30 per share.)
Under BMS’s current business paradigm, collaborative partnership arrangements to co-market and co-develop drugs with other pharmaceutical and biotechnology companies have come to play a major role in the growth of BMS’s drug pipeline and product offerings. According to a BMS spokesperson, products resulting from intercompany alliances now drive over 50% of their total drug sales.
Major recent alliances include a cardiovascular disease collaboration with Isis Pharmaceuticals, Carlsbad, California; a deal with Pfizer, New York City, to develop and commercialize anticoagulant and metabolic compounds; and an agreement with AstraZeneca, London, to product and market diabetes compounds.
The BMS commitment to new drug discovery is reflected in the size of its investment in research and development—related resources. Currently, the company’s research and development department employs over 7,000 people at four major U.S. facilities (supplemented by numerous other facilities distributed throughout the world).
According to BMS executives, the research reorientation of the last few years is not merely a matter of building a colossus-sized staff of scientists. It also entails a shift in the type of research being undertaken as BMS R&D places more and more of its emphasis upon high-risk, pioneering disciplines such as genomics and pharmacogenomics.
The result, according to numerous analysts, has been a more nimble and streamlined but still deep-pocketed operation that has effectively and efficiently transitioned itself— utilizing formidable industry alliances and a burgeoning pipeline—to meet the competitive challenges of today and tomorrow.
In a period of less than four years, BMS R&D has delivered eight new drugs to market. As the BMS website boasts “by industry standards, this (performance) places Bristol-Myers Squibb among the most productive pharmaceutical companies in the world today.” New products have included treatments for several major disease areas, including psychiatric disorders, HIV/AIDS, hepatitis B, rheumatoid arthritis, and cancer.
On an Oncologic Roll
Perhaps in no other therapeutic arena has this transformation been more evident than oncology. After a brief period of stagnation, the resurgent oncology division, according to numerous Wall Street analysts, stands poised to retake an oncology-treatment industry leadership position similar to the one it had held just under a decade ago.
The BMS oncology renaissance began in early 2004 with FDA approval of Erbitux, a colorectal cancer treatment co-developed and co-marketed with ImClone Systems, Inc., New York City. Since obtaining initial approval for the agent, BMS and ImClone have sought and obtained FDA approval in 2006 to expand Erbitux’s indication to encompass treatment of head and neck cancer. At the time of its approval, Erbitux represented the first new head and neck cancer treatment option in 45 years.
The foundation set by the Erbitux approval was further built upon in mid-2006 when BMS attained another FDA new oncology drug approval, this time for Sprycel, a therapy designed to treat chronic myeloid leukemia. The approval represented a significant affirmation of BMS’s dynamic response to quickly changing industry conditions. Unlike big pharma competitors of similar size, who have largely remained relevant via the exclusive reliance on checkbook-based strategies of acquisitions of and collaborative marketing agreements with hot, innovative biotech concerns, Sprycel was discovered and developed in-house by BMS scientists.
The year 2007 has seen BMS make continued advances on the oncology front. In September, Phase III study results demonstrated that Erbitux, in combination with platinum- based chemotherapy, met its primary endpoint of increasing overall survival compared with chemotherapy alone in patients with advanced non—small cell lung cancer.
Perhaps most significantly, October saw BMS win FDA approval for Ixempra, a novel agent indicated as monotherapy for the treatment of patients with advanced breast cancer, whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine. The FDA has also granted approval of Ixempra in combination with capecitabine for the treatment of patients with advanced breast cancer resistant to treatment with an anthracycline, and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated.
In the same month, the company acquired privately held Adnexus Therapeutics, Inc., Waltham, Massachusetts, developer of a new therapeutic class of biologics called adnectins, a proprietary class of targeted biologics based on a naturally occurring protein found in human serum. BMS and Adnexus had already shared a pre-existing relationship centered around the joint development and marketing of innovative biologic oncology therapies.
Journal of Clinical Oncology
In November, BMS announced the unveiling of a lower, more tolerable once-daily dosage regimen for Sprycel that reduces side-effect incidence while preserving efficacy. Also in November, data were published in the suggesting that Erbitux enables the complete surgical resection of colorectal liver metastases in patients previously refractory to conventional systemic therapy. (About 50% of patients with colorectal cancer will develop liver metastases during the course of their disease.) The research, which supports similar findings observed in other Phase II and III trials of Erbitux combined with irinotecan- or oxaliplatin-based chemotherapy in patients who have not received prior chemotherapy for their metastatic disease, demonstrated that patients with previously unresectable colorectal cancer can achieve substantial regression of their liver metastases with Erbitux therapy, thereby increasing the potential for these patients to become candidates for complete surgical resection of their metastatic disease. Medical experts assert that complete resection offers the only chance of long-term survival for this patient population.
Bristol-Myers Squibb Oncology Pipeline
Paraplatin (carboplatin aqueous solution)
Refractory solid tumors
Refractory or recurrent ovarian cancer
Multiple trials examining leukemia, refractory leukemia, previously treated malignancies, various types of advanced cancer, and various novel dosage formulations (i.e., five-times-daily bolus injection, six-hour infusion, 24-hour continual infusion)
Multiple trials examining patients with primary or metastatic liver cancer and altered hepatic function
Multiple colorectal cancer and metastatic colorectal cancer trials
Multiple trials examining advanced and metastatic non-small cell lung cancer
Paraplatin (carboplatin aqueous solution)
Multiple refractory solid tumor trials
Multiple trials examining advanced breast cancer, previously treated refractory breast cancer and various novel breast cancer treatment regimens, protocols, dosage formulations and combinations
Multiple bone cancer trials (advanced AIDS-related Kaposi’s Sarcoma)
Multiple head and neck cancer trials
Multiple trials examining recurrent, advanced and metastatic non-small cell lung cancer
Multiple trials examining novel dosing regimens and advanced, refractory and recurrent ovarian cancer
Hormone refractory prostate cancer
Cancer of the reproductive system
Multiple colorectal cancer, metastatic colorectal cancer, and advanced colorectal cancer trials
Multiple head and neck cancer trials
Multiple trials examining recurrent, advanced and metastatic non-small cell lung cancer
Multiple breast cancer trials examining various combination therapy regimens
Multiple trials examining recurrent, advanced and novel non-small cell lung cancer treatment regimens
Multiple advanced ovarian cancer trials
Head and neck cancer
Ovarian, breast, bone (Kaposi’s Sarcoma), and lung cancer
Colorectal and head and neck cancer
Chronic myeloid leukemia
The future outlook for 2008 and beyond appears robust. A glance at the current BMS oncology pipeline appears to confirm this outlook (Figure). Although the pipeline may not boast an overabundance of separate agents, the compounds that are being studied have a wide rage of potential applications across a diverse array of cancers. While BMS only has four agents in various stages of preclinical study, no less than 70 individual trials are currently underway. Thus, while BMS’s immediate future may not contain as many new drug approvals as its immediate past, the amount of new and expanded indications yielded will likely be impressive. Additionally, the Adnexus acquisition bodes well for oncology drug development prospects going forward.
Summing up the current state of his company, James M. Cornelius, CEO, BMS, stated “We’re making significant progress in identifying ways to operate more efficiently and reduce costs companywide as we maintain investments in our productive pipeline, which continues to yield important new therapies, including the recent addition of Ixempra for breast cancer. We’re also boosting our presence in biologics with the announced acquisition of Adnexus Therapeutics.”
%u25BA Prostate Cancer Partnership Begins to Bear Fruit
An oncology drug development alliance forged between Infinity Pharmaceuticals and MedImmune, Inc., wholly owned by AstraZeneca, continues to yield encouraging results. The two companies have announced that IPI-504, their lead heat shock protein 90 (Hsp90) inhibitor, has moved into Phase II clinical trials. (The small molecule drug candidate, IPI-504, is being jointly developed by Infinity and MedImmune.)
The study, currently enrolling subjects at San Bernardino Urological Associates Medical Group in San Bernardino, California, will evaluate the efficacy and safety of the agent in patients with advanced hormone-refractory prostate cancer (HRPC). As the enrollment process proceeds, research is expected to expand to additional sites including the Dana-Farber Cancer Institute, Massachusetts General Hospital, and the Beth-Israel Deaconess Medical Center in Boston, Massachusetts.
The open-label, multicenter study is designed to determine the antitumor activity of IPI-504 in patients with HRPC, also referred to as castration-resistant prostate cancer, and to correlate prior treatment status with clinical response. Two groups of patients will be enrolled. One group will have had no prior treatment with cytotoxic chemotherapy, and the other group will have had prior treatment with a Taxotere-based chemotherapy.
The agent being evaluated, IPI-504 will be administered by intravenous infusion at the recommended Phase II dose of 400 mg/m2 on a three-week cycle of therapy, consisting of twice weekly treatment for two weeks followed by one week off. Evidence of biological activity in both groups of patients will be evaluated by RECIST (Response Evaluation Criteria in Solid Tumors) and measurement of prostate-specific antigen levels. The trial is expected to enroll 30 patients initially (15 per group) and will expand to enroll an additional 10 patients in each trial arm if a response is observed in at least one patient in that arm.
“Hormone-refractory prostate cancer is a deadly disease with few effective therapeutic options for patients, particularly after docetaxel-based chemotherapy,” said William Oh, MD, Clinical Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and the trial’s principal investigator. “This trial is an important opportunity to assess the impact that IPI-504 may have on delaying disease progression for patients with HRPC,” asserted Dr. Oh.
Several proteins believed to be important in the progression of HRPC, including the androgen receptor, Akt and HER-2 are client proteins of Hsp90. Data from preclinical studies of IPI-504 in prostate cancer xenograft models indicate that Hsp90 inhibition may cause a dose-dependent degradation of these client proteins and growth inhibition of tumors.
“Initiating this trial in HRPC is an important milestone in our Hsp90 program,” stated David Grayzel, MD, Vice President, Clinical Development and Medical Affairs, Infinity Pharmaceuticals. “Based on the safety and biological activity demonstrated by IPI-504 to date, we are enthusiastic about our anticipated expansion into the investigation of additional clinical indications,” concluded Dr. Grayzel.
In separate, concurrent studies, IPI-504 is under ongoing evaluation in two other prospective solid-tumor indications. The agent is currently being evaluated in the expansion phase of a Phase I trial in patients with metastatic gastrointestinal stromal tumors and soft tissue sarcomas and in a Phase I/II combination trial in patients with advanced non—small cell lung cancer. “All of which are diseases where Hsp90 inhibition has a strong scientific rationale and there is a high unmet medical need for patients,” pointed out Dr. Grayzel.
The water-based formulation of IPI-504 is delivered as an intravenous infusion; the companies’ next-generation oral inhibitors of Hsp90 are currently in preclinical development.
%u25BA Avastin Shown To Halt Brain Cancer Progress
According to Phase II clinical trial data presented at the 12th Annual Scientific Meeting of the Society for Neuro-Oncology, held in Dallas, Texas, Avastin, manufactured by Genetech, has demonstrated encouraging six-month progression-free survival and objective response rates in patients with relapsed glioblastoma multiforme (GBM).
Genentech announced that both study arms of the randomized, multicenter trial yielded positive results in patients with GBM, the most common and aggressive form of brain cancer. The study enrolled 167 patients with GBM whose cancer had relapsed after first- or second-line therapy. All patients had received prior temozolimide.
In one arm of the study, patients were administered Avastin as a stand-alone therapy. In the other arm, Avastin was given in combination with irinotecan chemotherapy. Patients were randomized to receive Avastin alone or in combination with irinotecan every other week for up to 104 weeks. An assesment undertaken via independent radiological review found that 36% (or 31 of the 85) patients treated with Avastin alone, and 51% (or 42 of the 82) patients treated with the Avastin/chemotherapy combination lived free of disease progression for the entire six-month study period.
In addition to progression-free survival, researchers also analysed tumor response in study subjects. According to preliminary estimates, tumor response was observed in 21% (or 18 of the 85) of patients treated with Avastin alone and 34% (or 28 of the 82) of patients treated with both Avastin and chemotherapy.
Avastin was also shown to be relatively safe and well-tolerated by members of the study population. No new or unexpected adverse events were observed in the study participants who underwent Avastin treatment. Adverse events that did occur (i.e., most commonly hypertension and convulsion) were similar in nature to those previously reported in other Avastin studies.
According to the lead investigator of the research, Timothy Cloughesy, MD, Director, Neuro-Oncology Program of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, the progression-free survival results are particularly significant because, according to various historical estimates, only about 15% of those afflicted with GBM show no evidence of disease progression over six-month increments of time.
The study is ongoing and final analyses for safety and other efficacy endpoints will be available in 2008. Hal Barron, MD, Senior Vice President, Development and Chief Medical Officer, Genentech, reported that the findings “exceeded our expectations.”
Avastin, an antibody, is designed to inhibit vascular endothelial growth factor (VEGF), a protein that plays an important role in angiogenesis and the maintenance of existing blood vessels throughout the lifecycle of a tumor. By inhibiting VEGF, Avastin interferes with the blood supply to a tumor, which is thought to be critical to a tumor’s ability to grow and metastasize.
The FDA first approved Avastin in early 2004 as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FUbased chemotherapy. Avastin is also indicated in combination with intravenous 5-FU-based chemotherapy for second-line treatment of patients with metastatic carcinoma of the colon or rectum. In 2006, the FDA approved Avastin in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non—small cell lung cancer.
According to the American Cancer Society (ACS), the five-year survival rate for patients with GBM has remained static at 3% for more than a quarter-century. The ACS estimates there will be 20,500 new cases of brain cancer and 12,740 brain cancer deaths in 2007.
In related news, Genentech is seeking regulatory approval for Avastin to be used by breast-cancer patients, increasing its annual potential sales by $1.3 billion. A final FDA decision on the potential indication expansion is expected in February 2008. Avastin is currently being studied worldwide in more than 300 clinical trials examining the agent’s efficacy in the treatment of 20 different tumor types.
%u25BA Melanoma Treatment Candidate Enters Phase II
A Phase II clinical trial designed to examine the efficacy and safety of a potential metastatic malignant uveal melanoma treatment has recently been initiated and is currently underway. Hana Biosciences has announced that it has commenced dosing the first of the patients who are participating in the Phase II trial with Marqibo (vincristine sulfate injection, Optisome).
Marqibo is an optisomal formulation of vincristine. Optisomes are a new generation of unique, sphingomyelin/ cholesterol-based nanoparticles designed to encapsulate cell cycle—specific chemotherapeutics and preferentially transfer these therapies to cancer sites, improving efficacy while reducing toxicity in the process. Vincristine, a microtubule inhibitor, kills cancer cells when they enter a very specific point in the cell cycle, and its efficacy is concentration- and exposure duration–dependent. Marqibo is believed to extend the circulation time of vincristine in the bloodstream, increase targeting of the drug to malignant cells, and enhance exposure duration at the site of the disease. Unlike regular vincristine, Marqibo is dosed based on patient body surface area and its dose does not need to be limited in order to avoid neurotoxicities.
The primary objective of the Phase II research is to assess the efficacy of Marqibo. Efficacy will be determined by an analysis of response rates.
Other objectives of the study include assessment of Marbiqo’s safety and antitumor activity via such secondary endpoints as response duration, time to progression, and overall survival.
Patient population parameters encompass adults with uveal melanoma and confirmed metastatic disease that is untreated or that has progressed following one prior therapy. The trial is headquartered at the MD Anderson Cancer Center at the University of Texas, Houston. At least 30 patients are expected to participate.
The Phase II clinical trial is supported and made possible by data from a Phase I trial of Marqibo, which demonstrated encouraging single-agent activity, in patients with metastatic melanoma originating in the eye. These data were reported in early 2007 at the 43rd American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, by Dr. Patrick Hwu, Chair, Melanoma Medical Oncology at the University of Texas MD Anderson Cancer Center.
In the Phase I study, an objective response rate (complete response plus partial response) of 13% and stable disease rate of 20% was achieved among 15 patients with histologically confirmed, surgically nonresectable metastatic cutaneous, mucosal, or uveal melanoma. One of four subjects with uveal melanoma metastatic to the lung achieved a complete response. Marqibo was generally well tolerated and showed promising single-agent activity against metastatic melanoma.
According to the principal investigator of the trial, Agop Y. Bedikian, MD, Professor in the Melanoma Medical Oncology Department at the University of Texas MD Anderson Cancer Center, the potential treatment is offering a dose of much needed hope to sufferers of a disease state who have heretofore had little reason for optimism. This is due to the fact that, in general, patients with metastatic uveal melanoma do not tend to respond to systemic chemotherapy and therefore have limited treatment choices. If Marqibo continues its progress through the clinical trial process, the agent may eventually provide a very necessary and beneficial additional treatment option.
“We are excited to initiate this Phase II trial based on clinical data that suggest that Marqibo has promising activity in melanoma, in addition to its potential in treating hematologic malignancies. We are delighted to collaborate with worldrenowned oncology experts like Dr. Bedikian and his team at MD Anderson Cancer Center to explore the potential of our novel therapeutics to improve treatment outcomes for patients with difficult-totreat cancers,” stated Steven R. Deitcher, MD, President and CEO of Hana Biosciences.
Uveal melanoma is a cancer of the colored part of the eye and the surrounding areas, called the uvea. Uveal melanoma is the most common primary intraocular malignant tumor in adults and represents 5% to 6% of all melanoma diagnoses.
Marqibo has shown promising anticancer activity in patients with acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, and melanoma in several clinical trials. Vincristine is FDA-approved as a monotherapy and in combination regimens for the treatment of hematologic malignancies such as lymphomas and leukemias.
%u25BA Celgene and Pharmion to Join Forces
Pharmion, the high-flying biotech concern that had seen its stock more than double during 2007, is being acquired by New Jersey—based Celgene. The terms of the purchase, a cash and stock deal valued at $2.9 billion, represent roughly a 50% premium (as quantified prior to Pharmion’s approximately 30% surge on the day following the announcement of the acquisition) over Pharmion’s closing stock price at the time of the merger’s announcement.
Wall Street analysts generally responded positively to the transaction, tending to characterize the move as sensible and sound. The marriage will help to reinforce Celgene’s prominent position as a dominant player in the biotechnology marketplace. Prior to attaining Pharmion, Celgene, largely due to the robust sales (over $300 million during the last fiscal quarter for which data are available) of its effective and expensive multiple myeloma treatments, was already one of the largest biotechs in the industry, ranking fourth in market capitalization and seventh in total sales. Perhaps more importantly than providing a boost in sheer size, however, the acquisition is expected to significantly bolster Celgene’s strength in the oncology sector.
The future prospects of Pharmion’s flagship drug, a blood cancer therapy branded as Vidaza, are thought to be particularly promising. According to a study released in August 2007, Vidaza was demonstrated to increase survival by 74% in patients with a severe form of myelodysplastic syndrome (MDS) a set of rare, high-risk blood disorders. In total, Pharmion has four currently approved oncology prod- ucts on the market. Pharmion also has blood and small-cell lung cancer therapies in various stages of development that have been posting impressive results in clinical trials. Several other prospective products in development focus upon various hematological and solid tumor cancers.
According to Sol J. Barer, PhD, Chairman and Chief Executive Officer, Celgene, the tactical attractiveness and synergies inherent in the union are clear. Commenting on the reasons for the move, Dr. Barer explained, “The acquisition of Pharmion is an exceptional strategic fit that will expand our role as a leader in hematology and oncology. Our combined global infrastructure will leverage the therapeutic and commercial potential of Pharmion’s products, particularly Vidaza, which has the potential to become a major global therapy. By bringing together the talents and resources of both companies, we move closer to our vision of becoming a leading hematology and oncology company in the world, expanding our industry leading programs for safety, access, and patient support.”
Celgene and Pharmion have been partners in some form since 2001, when Pharmion began selling Thalomid in Europe and Celgene acquired an equity stake in the smaller company. Thalomid, which is indicated to treat multiple myeloma and leprosy, is Celgene’s top selling therapy. Pre-merger, Pharmion had possessed marketing rights to the agent in all markets outside the United States. Revlimid, basically an improved version of Thalomid, is Celgene’s second most popular product. In addition to treating multiple myeloma, Revlimid is also approved to combat MDS.
Celgene’s market research data state that 15% of all patients with MDS are treated with either Revlimid or Vidaza. The two drugs do not compete with one another, as they are used for different forms of the disease. Vidaza is utilized to treat a far more severe form of MDS than Revlimid. The Celgene—Pharmion merger is expected to close in the second quarter of 2008. Analysts expect that the costs of the Pharmion acquisition will be slightly dilutive to Celgene’s 2008 earnings. Although analysts speculate that the transaction will represent a short-term setback for Celgene’s pershare price, the general consensus is that the company attained good value for its purchase and could see as much as $1 billion in top-line return-on-investment as soon as 2012.
The exact manner in which the combined companies will use their sales forces is still unclear. One possibility is that one company's sales force will market products to doctors who specialize in MDS, and the other will market products that treat multiple myeloma.
%u25BA Follicular Lymphoma Treatment Hits Phase III Primary Endpoint
Bayer Schering Pharma AG, Berlin, has announced that its potential follicular lymphoma treatment, Zevalin, has attained a demonstrated improvement in progression-free survival, the primary endpoint set by researchers conducting the First-Line Indolent Trial (FIT), a major, multinational, randomized Phase III trial.
Zevalin is designed to serve as a first-line consolidation therapy indicated for patients suffering from advanced follicular lymphoma, one of the most common types of non-Hodgkin lymphoma (NHL), a type of malignant disease that occurs within the lymphatic system. It is the fifth most common cancer after breast, prostate, lung, and colon cancer. Consolidation therapy is a treatment regimen given after a patient responds to initial first-line induction therapy (i.e., chemotherapy, immunochemotherapy). The aim of consolidation therapy is to rapidly improve the quality of a patient’s response, thereby extending the duration of that response.
In the late-stage trial, patients with stage III and stage IV follicular lymphoma received either Zevalin or no further treatment after showing at least a partial response (i.e., either partial or complete remission) to initial induction treatment. Patients in the Zevalin study arm experienced longer-term rates of progression-free survival when compared with the patients in the observation arm.
Kemal Malik, MD, Head of Global Development, Bayer Schering Pharma AG, explained, “Despite improvements in recent years, follicular lymphoma is still challenging to treat and many patients experience a relapse following treatment. An important goal of consolidation therapy is to ensure that, for patients who respond to initial induction therapy, the quality of their response is improved and therefore, their remission period is long-lasting. The aim of FIT was to see in a randomized, prospective clinical trial setting if a single therapeutic dose of Zevalin as first-line consolidation therapy could achieve this important goal.”
According to its manufacturer, Zevalin merges the tumor-targeting ability of an anti-CD20 monoclonal antibody with the tumor-destroying power of localized yttrium-90 radiation, resulting in an efficacy that is better than non-radio-labelled immunotherapy alone. The radio-labelled antibodies can specifically bind to the tumor, killing targeted as well as neighboring lymphoma cells, destroying the tumor through several layers of tumor cells.
Full and complete results from the Phase III FIT trial were presented on December 10, 2007, at an oral presentation entitled “[90Y]-ibritumomab tiuxetan (Zevalin) consolidation of first remission in advanced stage follicular NHL: First results of the international randomized Phase III First-line Indolent Trial (FIT),” which was delivered during the 49th Annual Meeting of the American Society of Hematology (ASH), held at the Georgia World Congress Center in Atlanta, Georgia, from December 8-11, 2007.