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Market Research in the Healthcare Field with Expertise in Medical Imaging and Radioisotopes
Bio-Tech Systems, Inc. - 4167 West Pinecrest Circle - Las Vegas, Nevada 89121 phone: (702) 456-7608 - fax: (702) 456-2189
New Promise for Therapeutic RadiopharmaceuticalsMar. 19, 2006
It will also offer an attractive investment opportunity for many of the companies and venture groups supporting these programs. These agents will be used in conjunction with traditional therapies, enhancing their effectiveness, with better specificity and reduced side effects. The market for therapeutic radiopharmaceuticals was still on the threshold in 2005, with total sales of $71 million. Rapid growth is anticipated over the next 5-6 years. By 2012, therapeutic product sales should reach $1.9 billion, with high continuing growth beyond that time. As interest in new therapeutic radiopharmaceuticals increases, it is prompting investigators to utilize isotopes with more focused capabilities for treating various tumors, reducing the negative effect on neighboring healthy cells. Whereas current therapeutic radiopharmaceuticals have employed only two isotopes, yttium-90 and iodine-131, future products will employ both beta and alpha emitters where the shorter particle range and high-energy deposition can be used to advantage to destroy DNA directly. There are a number of products in development employing lutetium-177, promethium-149, bismuth 212, bismuth-213, astatine-211, radium-223 and polonium 210. Historical Perspective
The market for therapeutic radiopharmaceuticals crossed a major threshold in 2002 with the approval of Zevalin (Biogen Idec) for treating non-Hodgkins lymphoma. This was followed in 2003 with the approval of Bexxar (Glaxo SmithKline) for similar indications. Zevalin is based on Rituxan (Biogen Idec) an antibody product for the treatment of non-hodgkins lymphoma. With Zevalin, yttium-90 is linked to the antibody adding the therapeutic effect of the isotope to target the lymphoma cells.Prior to the introduction of Rituxan, there were no targeted therapies for lymphoma and the outcomes were poor for many patients. Therefore, Rituxan added significantly to the treatment options and it has been extremely effective in treating patients resistant to more conventional therapies. In fact, Rituxan has become the most widely distributed oncology drug in the world and has reached blockbuster status with sales of $1.6 billion per year. Nine other antibody products have been approved since 2002 with growing market acceptance. These technologies create a good platform for conveying therapeutic isotopes to enhance performance in cancers resistant to traditional therapies. The Learning Curve
One would imagine that the success of Rituxan would create an excellent platform for Zevalin because of the proven success of the underlying antibody. However, this has not been the case. Medical oncologists have been resistant to referring their patients out of their practice to radiation oncologists qualified to administer radioactive drugs. Since oncologists derive a significant portion of their income from administering chemotherapeutic drugs, they tend to wait until all options are exhausted before referring patients to other physicians.The lymphoma patients referred to radiation oncologists for treatment with Zevalin have already failed the basic antibody treatment and are less likely to respond than if they were referred earlier before their condition deteriorated. So, in one way the success of Rituxan has worked against the wider use of Zevalin even though the potential exists to improve the outcome for many patients. Notwithstanding these limitations, sales of Zevalin and Bexxar have been increasing gradually as both companies work to educate oncologists of the potential benefits. On the positive side, therapeutically targeted radiation has been validated with Zevalin and Bexxar. This has led to a surge in research activity to expand applications for therapeutic radiopharmaceuticals. Current approaches employ more sophisticated targeting methodologies and more appropriate therapeutic isotopes for the tumors being treated. There is also more confidence in the investment community with respect to the prospects for FDA approval of these drugs. Therapeutic Pipeline Products
Table 1 provides an overview of therapeutic radiopharmaceuticals in the research pipeline. The list provides a good idea of the range of ongoing research activities with emphasis on cancers with high incidence such as lung cancer, prostate cancer, breast cancer and colon cancer. The list also includes some of the international firms that plan to introduce products in the US.
Major Progress in International Cooperation
As cancer research has accelerated worldwide, communication has improved, allowing researchers internationally to share information more openly with colleagues in the US. One example is an American product developed by Peregrine Pharmaceuticals (I-131 Cotara TNT) has recently been approved for brain cancer therapy in China. With the data derived, it will help Peregrine and others to better understand the potentials of this technology, hopefully accelerating FDA approval in the US.In another case, Dr. Eric Krenning and Dr. Marion de Jong at Erasmus Medical Center in The Netherlands have been doing some landmark research with peptide receptor radiation therapy with Y-90-DOTA0, Tyr3-Octreotide and Lu-177-DOTA0, Tyr3-Octreotate. These are somatostatin analogs that are directed toward neuroendocrine tumors. They have treated over 100 patients with excellent results by utilizing a unique patient specific dosimetry, optimizing the dosage for each patient to minimize renal toxicity. Russian American Cancer Alliance
The Russian American Cancer Alliance was approved by the US Congress for the purpose of supporting cooperative cancer research programs for its members. The US, charter members are the Fox Chase Cancer Center in Philadelphia and the University of Maryland Greenbaum Cancer Center. One of the primary Russian participants is the Kurcharov Nuclear Research Institute. This is a federal facility that supplies isotopes to the Russian American Cancer Alliance through its network and affiliations with other nuclear facilities in Russia. The Alliance also supplies isotopes to nonmember facilities, but does not sell the isotopes. All of the relationships are partnerships whereby Grants are shared in research agreements. This is advantageous since there are a number of isotopes available in Russia that are not offered in the US.New Technology Opportunities
Two approaches are being pursued with therapeutic radiopharmaceuticals: 1) antibody-based drugs and 2) targeted peptides linked to therapeutic isotopes. There is more experience with antibody-based drugs and they appear to offer less of a challenge in terms of renal toxicity. The peptides are smaller molecules that clear more rapidly, but tend to be more toxic to the kidneys. However, antibody products have their own problems in terms of large molecule size that circulate for long periods of time.One approach that has stimulated considerable interest is bispecific antibodies that allow pretargeting, where the drug is administered in two stages. The target antibody is first administered in nonradioactive form. This seeks out the tumor receptors and locks on to them. The unassociated antibody is then allowed to clear the system. A second injection is made later with the radioactive component. This has a linker that seeks out the free arm of the bispecific antibody, minimizing the radioactive material in circulation. Immunomedics has been pursuing this approach for some time and has reported promising results. Another growing area of interest is the use of agonists, which seek out tumors and stimulate cellular growth. However, the agonists are linked to a therapeutic isotope that destroys the cell internally. Bombesin is the agonist commonly linked to yttrium-90 or lutitium-177 that target GRP (gastrin releasing peptide) receptors. These receptors are found in lung cancer, prostate cancer and breast cancer as well as other tumors. Bracco has initiated clinical trials in Europe and there are others who are investigating this class of drugs. Increased Use of Alpha Emitters
There is considerable research involving alpha emitters, where the shorter particle range and high-energy deposition can be used to advantage to destroy DNA directly. There are a number of products in development employing bismuth 212, bismuth-213, astatine-211 and polonium-210.One unique approach involves an in vivo generator where lead-212 decays to bismuth-212. The parent isotope (lead-212) is targeted to disseminated melanoma tumors utilizing a melanocortin targeting agent. The in vivo use of the parent isotope allows one to deliver 10 times the energy than would otherwise be possible. The parent is chelated in an inorganic metal chelator that is attached to the targeting peptide. The peptide then binds to the receptor, where the entire receptor-radiolabeled peptide complex is internalized in the tumor cell. The lead-212 then decays to bismuth-212 and the bismuth produces the alpha energy. Lead 212 is a mild beta emitter that goes through the system safely, reducing radiation to the kidneys. In this application, there is also low risk to the bone marrow because the peptide is small and most of it gets out of circulation quickly. Importance of Patient Specific Dosimetry
One of the limiting factors in utilizing therapeutic radiopharmaceuticals is the potential hazard to the bone marrow, kidneys and other internal organs. The smaller peptide molecules may get out of the system rapidly but still cause damage as they pass through the various organs. The tolerable limits vary from patient to patient depending on the volume of the kidneys and other critical organs, rate of excretion and other factors that vary from one individual to another. Therefore, it is important to determine the therapeutically effective dose for each patient.In the simplified model normally associated with regulatory approval, dosages are estimated based on patient weight and other physical factors rather than radiation absorbed dose. The net effect is that large safety factors are utilized to compensate for the unknowns, often resulting in dosages that are too low to be clinically effective. With the availability of molecular imaging and PET-CT, one can determine the mean residence time of the tracer in each of the organs of interest. This allows one to examine the risk of tissue damage and select the greatest effective dose for each patient. Although there are a limited number of positron emitters suitable for imaging, such as yttrium-86, iodine-124 and copper-64, their availability is increasing. In conventional chemotherapy, the physician often determines the dose in terms of how many times the drug is administered and how many doses the patient can tolerate. During the process, the physician tracks blood levels and known toxic reactions in the body in the heart, liver, etc. This information is used to try and limit the side effects. However, this is more difficult with radiotherapeutic drugs where there is only one infusion. In the final analysis, treating cancer with drugs is a trial and error process. Some patients may respond better to one drug than another, even though superficial indications and symptoms are the same. This allows the clinician to try new therapeutic drugs in resistant cases, with the hope that it will produce a positive response. As new therapeutic radiopharmaceuticals enter the mainstream, it will stimulate the development of a large array of related products targeted to many different types of tumors. Molecular Imaging will be merged with therapy to obtain patient specific dosimetry for optimizing patient response and minimizing side effects. This should bring oncologists and nuclear physicians closer together, with a better understanding of nuclear medicine’s potentials. With this type of market stimulus, it is likely that many more traditional pharmaceutical companies will enter the field with radioactive versions of targeted therapeutic products in order to enhance treatment options for many cancer patients. by Marvin Burns
Mar. 19, 2006 BIO-TECH SYSTEMS, INC., founded in 1980, provides clients with market research services in the healthcare field. This focuses on strategic planning, market research and development of new business opportunities. Bio Tech specializes in product and market evaluation where technical insight is important as well as the ability to communicate with many levels of management and end-users. One objective is to assess technological risk and target new products and services effectively in order to generate the best market response. Bio-Tech's expertise is in medical imaging and radioisotope products covering a broad range of diagnostic and therapeutic applications. For further details and information, please visit us at: Related Reading:
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