BOULDER, Colo., Jan. 23 /PRNewswire-FirstCall/ -- Pharmion Corporation today announced the submission of a marketing authorization application (MAA) with the European Medicines Agency (EMEA) for Thalidomide Pharmion for the treatment of untreated multiple myeloma in the European Union (E.U.). The submission includes details of the Pharmion Risk Management Programme (PRMP) as a condition of supply following the approval of Thalidomide Pharmion.
“This submission represents the achievement of a significant milestone for Pharmion. We look forward to working with the EMEA, as well as patient and Thalidomider groups as we proceed through the regulatory process,” said Patrick J. Mahaffy, Pharmion’s president and chief executive officer. “The data for Thalidomide in the treatment of untreated multiple myeloma are extremely positive and we believe that it is time for this very important and widely used drug to come under regulatory oversight.”
Multiple myeloma, the second most common cancer of the blood, affects approximately 82,000 people in the E.U., and approximately 25,000 people in the E.U. are diagnosed with multiple myeloma each year.
“Our data demonstrate significant benefit when Thalidomide is added to today’s standard of care in untreated elderly patients with multiple myeloma,” said Philippe Moreau, Professor of Clinical Haematology at Nantes Faculty of Medicine and Chairman of the Intergroup Francophone du Myelome (IFM). “Based on these data, and particularly the unprecedented 21-month survival advantage demonstrated for the Thalidomide arm, we believe that Thalidomide, melphalan and prednisone should rapidly become the reference therapy for this patient population. We hope the EMEA acts urgently to approve this very critical therapy,” he added.
Thalidomide Pharmion has been designated as an Orphan Medicinal Product in the E.U. for the treatment of multiple myeloma, which, if approved, entitles the drug to ten years of market exclusivity for the approved indications.
The application is based upon a clinical data package comprised of four studies in more than 1400 patients. These studies, which include both first-line and induction therapy, include:
* IFM 99-06, a three-arm study conducted by IFM, demonstrated the superiority of melphalan/prednisone plus Thalidomide (MPT) over standard therapy of melphalan/prednisone (MP) or a combination of chemotherapies (vincristine/adriamycin/dexamethasone, or VAD) followed by melphalan and transplantation (MEL 100) in the treatment of newly diagnosed elderly multiple myeloma patients. A total of 447 patients were randomized to one of the three treatment arms. Following an interim analysis, recruitment was stopped on the recommendation of the study’s Data Safety Monitoring Board (DSMB). At final analysis, the median overall survival in the MPT arm was approximately 53.6 months, compared to 32.2 and 38.6 months, respectively, for the MP and MEL 100 arms. Thalidomide treatment was well-tolerated by the majority of patients. The Thalidomide combination was associated with more venous thrombosis and pulmonary embolism. Patients taking thalidomide were also at more risk of peripheral neuropathy, neutropenia and constipation.(1) * A study conducted by the Italian research group Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) also demonstrated the superiority of melphalan/prednisone plus Thalidomide compared to melphalan/prednisone alone. In the randomized study of MPT versus MP alone in 255 elderly patients, MPT had a superior response rate and a significantly higher two-year event-free survival rate (54 percent versus 27 percent).(2) * MM-003, a Phase 3, multi-national, placebo controlled, randomized study of 470 patients, sponsored by Celgene Corporation and supported by Pharmion, compared Thalidomide plus dexamethasone versus dexamethasone and placebo in newly-diagnosed patients. In December 2005, an Independent Data Monitoring Committee reviewed the data as part of a pre-specified interim analysis and concluded that the study should be stopped as it had reached its efficacy stopping rule of p<0.0015 for the primary endpoint of time to disease progression. At the final analysis there was also a significant (p=0.001) improvement in response rate of Thalidomide plus dexamethasone of 69.4 percent, compared to dexamethasone and placebo of 51.1 percent. Of the Thalidomide treated patients, 43.8 percent experienced “Very Good” or “Complete Response” compared to 15.8 percent in the placebo arm (p<0.0001). Time to disease progression was 97.7 weeks versus 28.3 weeks.(3) * A Phase 3 study conducted by the Eastern Cooperative Oncology Group (ECOG) compared Thalidomide plus dexamethasone compared to dexamethasone alone in over 200 patients. The study demonstrated a statistically significant difference in response rates of 61.6 percent versus 39.6 percent (p=0.001) at four months with Thalidomide plus dexamethasone compared to dexamethasone alone.(4)
The Company is seeking approval for the following indications: Thalidomide Pharmion in combination with melphalan and prednisone for the treatment of patients with untreated multiple myeloma aged 65 years or older or ineligible for high dose chemotherapy and Thalidomide Pharmion in combination with dexamethasone for induction therapy prior to high dose chemotherapy and bone marrow transplant, for the treatment of patients with untreated multiple myeloma. Thalidomide Pharmion must be prescribed and dispensed through the Pharmion Risk Management Programme.
Thalidomide Pharmion is approved in Australia, New Zealand, Turkey, Israel, South Korea and Thailand for the treatment of multiple myeloma after the failure of standard therapies.
In markets where Thalidomide Pharmion is not approved, such as the E.U., Thalidomide Pharmion is currently provided on a named patient/compassionate use basis and under an Autorisation Temporaire d’Utilisation (ATU) in France while the Company seeks an approval. Pharmion is the only provider of thalidomide outside of the U.S. with a comprehensive safety program in place. The Company holds exclusive marketing and distribution rights from Celgene Corporation for Thalidomide in markets outside of North America, Japan and certain other Asian countries. In May 2006, Thalomid(R) (thalidomide) was approved by the U.S. Food and Drug Administration (FDA) in combination with dexamethasone for the treatment of newly diagnosed multiple myeloma.
Safety Information
Teratogenic effects:
If Thalidomide is taken during pregnancy, it can cause severe birth defects or death to an unborn baby. A single dose (one capsule) taken by a pregnant woman during her pregnancy can cause severe birth defects. Thalidomide should never be used by women who are pregnant or could become pregnant. Male and female patients must follow the contraception measures in the Pharmion Risk Management Programme.
The common adverse reactions associated with the use of Thalidomide in combination with other anti-myeloma therapies are: deep vein thrombosis, constipation, peripheral oedema, tremor, dizziness, fatigue, asthenia, somnolence, peripheral neuropathy, neutropenia, lymphopenia, leucopenia, anaemia, thrombocytopenia, paraesthesia and dysaesthesia. Serious or severe reactions associated with Thalidomide use are: deep vein thrombosis and pulmonary embolism, bradycardia, cerebrovascular accident, peritonitis, orthostatic hypotension, and severe skin reactions including Stevens Johnson Syndrome and toxic epidermal necrolysis. Thromboprophylaxis should be used when Thalidomide is prescribed in combination with other anti-myeloma therapies. Peripheral neuropathy is a potentially severe, adverse effect of treatment with Thalidomide that may result in irreversible damage. Thalidomide may also potentially aggravate existing neuropathy and should therefore not be used in patients with clinical signs or symptoms of peripheral neuropathy unless the clinical benefits outweigh the risks. Symptoms may occur some time after thalidomide treatment has been stopped and may resolve slowly or not at all. Thalidomide frequently causes drowsiness, somnolence and sedation. Patients should be instructed to avoid situations where drowsiness may be a problem.
About Multiple Myeloma
Multiple myeloma (also known as myeloma or plasma cell myeloma) is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. However, most patients with multiple myeloma have cells that produce a form of immunoglobulin called paraprotein (or M protein) that does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors. The cause of the disease is unknown.
About Pharmion
Pharmion is a biopharmaceutical company focused on acquiring, developing and commercializing innovative products for the treatment of hematology and oncology patients in the U.S., Europe and additional international markets. Pharmion has a number of products on the market including the world’s first approved epigenetic drug, Vidaza(R), a DNA demethylating agent. For additional information about Pharmion, please visit the company’s website at www.pharmion.com.
References 1. Facon et al. Data on file. 2. Palumbo, A, et al. 2006. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: a randomized controlled trial: Lancet 367,825-831. 3. Rajkumar et al. J Clin Oncol. 2006; 24 (185): 7517 and data presented at the American Society of Hematology 48th Annual Meeting and Exposition in, Orlando, 2006. 4. Rajkumar SV, Blood E, Vesole D et al. The Phase III clinical trials of thalidomide plus dexamethasone compared to dexamethasone alone in newly diagnosed multiple myeloma patients: A clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006; 24(3):431-6.
Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995: This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements are based on current expectations and involve a number of known and unknown risks and uncertainties that could cause Pharmion’s future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include the regulatory status and timing of regulatory approvals for Thalidomide; the impact of competition from other products sold by Pharmion’s competitors in the E.U.; the regulatory environment and changes in the health policies and structure of various countries; acceptance and demand for new pharmaceutical products and new therapies, uncertainties regarding Pharmion’s ability to enforce market exclusivities in member states of the E.U.; failure of third-party manufacturers to produce the product volumes required on a timely basis, fluctuations in currency exchange rates, and other factors that are discussed in Pharmion’s filings with the U.S. Securities and Exchange Commission. Forward-looking statements speak only as of the date on which they are made, and Pharmion undertakes no obligation to update publicly or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.
Pharmion Corporation
CONTACT: Breanna Burkart or Anna Sussman, Directors, Investor Relationsand Corporate Communications of Pharmion Corporation, +1-720-564-9150
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