U.S. District Court for the District of Delaware Concurrently Denies Motion For Preliminary Injunction Filed by Antares Pharma, Inc.
Chicago, IL, July 14, 2014
Medac Pharma, Inc., a privately held pharmaceutical company focused on the development of new molecules and improving the effectiveness of existing medicines, announced that the U.S. Food and Drug Administration (FDA) has approved Rasuvo™, a subcutaneous injectable methotrexate (MTX) therapy delivered in an auto-injector for rheumatoid arthritis (RA), polyarticular-course juvenile idiopathic arthritis (pJIA) and psoriasis. Rasuvo will be available in 10 dosage strengths, ranging from 7.5 mg to 30 mg in 2.5 mg increments and will be launched in the U.S.
The company concurrently announced that the U.S. District Court for the District of Delaware has denied a motion for a preliminary injunction filed by Antares Pharma, Inc.
“We’re delighted to have secured approval for our lead product, Rasuvo, and look forward to introducing this much-needed therapy to the market,” stated Ms. Terri Shoemaker, President and CEO of Medac Pharma, Inc. “Methotrexate has long been recognized as a mainstay in rheumatoid arthritis therapy. With its virtually painless administration, broad dose range, and significantly enhanced bioavailability, we believe Rasuvo may benefit those patients using methotrexate.” Regarding the U.S. District Court for the District of Delaware’s decision, Ms. Shoemaker stated, “We’re pleased with the Court’s decision and are moving forward with our commercialization efforts as planned.”
With more than 30 years of clinical usage, MTX remains the most commonly used drug for treating RA and is recommended by both the American College of Rheumatology and European League Against Rheumatism as a first-line therapy for RA patients. While many patients prescribed MTX take an oral form of this drug, this route of administration has been associated with highly variable absorption rates and inconsistent bioavailability among patients.
Medac Pharma, Inc. developed Rasuvo to optimize MTX therapy. The subcutaneous mode of delivery of Rasuvo, with its wide range of dosing options, has been designed to improve bioavailability.
Rheumatologist Eric Ruderman, MD, Professor of Medicine, Northwestern University Feinberg School of Medicine, stated, “As a rheumatologist, I believe Rasuvo will offer patients the opportunity to maximize the benefit they get from methotrexate. Rasuvo’s dosing flexibility, in particular, will be very helpful, as RA patients do not all respond equally to methotrexate, making it important to select a treatment regimen that is appropriate for the patient’s condition.”
For complete prescribing information, including Boxed Warning, please visit www.Rasuvo.com.
Indications and Important Safety Information Including Boxed Warning
Rasuvo is a folate analog metabolic inhibitor indicated for the:
- Management of patients with severe, active rheumatoid arthritis (RA) and active polyarticular juvenile idiopathic arthritis (pJIA), who are intolerant of or had an inadequate response to first-line therapy.
- Symptomatic control of severe, recalcitrant, disabling psoriasis in adults who are not adequately responsive to other forms of therapy.
Limitations of Use
Rasuvo is not indicated for treatment of neoplastic diseases.
This product includes the following Black Box Warning:
WARNING: SEVERE TOXIC REACTIONS, INCLUDING EMBRYO-FETAL TOXICITY AND DEATH
Rasuvo should be used only by physicians whose knowledge and experience include the use of antimetabolite therapy. Because of the possibility of serious toxic reactions (which can be fatal), Rasuvo should be used only in patients with psoriasis or rheumatoid arthritis with severe, recalcitrant, disabling disease which is not adequately responsive to other forms of therapy. Deaths have been reported with the use of methotrexate in the treatment of malignancy, psoriasis, and rheumatoid arthritis. Patients should be closely monitored for bone marrow, liver, lung, skin, and kidney toxicities. Patients should be informed by their physician of the risks involved and be under a physician’s care throughout therapy.
1. Methotrexate has been reported to cause fetal death and/or congenital anomalies. Therefore, Rasuvo is not recommended for females of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks. Rasuvo is contraindicated in pregnant women.
2. Methotrexate elimination is reduced in patients with impaired renal functions, ascites, or pleural effusions. Such patients require especially careful monitoring for toxicity, and require dose reduction or, in some cases, discontinuation of Rasuvo administration.
3. Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and gastrointestinal toxicity have been reported with concomitant administration of methotrexate (usually in high dosage) along with some nonsteroidal anti-inflammatory drugs (NSAIDs).
4. Methotrexate causes hepatotoxicity, fibrosis and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequently seen. These are usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have been reported; these latter lesions may not be preceded by symptoms or abnormal liver function tests in the psoriasis population. For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long-term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the rheumatoid arthritis population.
5. Methotrexate-induced lung disease, including acute or chronic interstitial pneumonitis, is a potentially dangerous lesion, which may occur acutely at any time during therapy and has been reported at low doses. It is not always fully reversible and fatalities have been reported. Pulmonary symptoms (especially a dry, nonproductive cough) may require interruption of treatment and careful investigation.
6. Diarrhea and ulcerative stomatitis require interruption of therapy: otherwise, hemorrhagic enteritis and death from intestinal perforation may occur.
7. Malignant lymphomas, which may regress following withdrawal of methotrexate, may occur in patients receiving low-dose methotrexate and, thus, may not require cytotoxic treatment. Discontinue Rasuvo first and, if the lymphoma does not regress, appropriate treatment should be instituted.
8. Like other cytotoxic drugs, methotrexate may induce “tumor lysis syndrome” in patients with rapidly growing tumors.
9. Severe, occasionally fatal, skin reactions have been reported following single or multiple doses of methotrexate. Reactions have occurred within days of oral, intramuscular, intravenous, or intrathecal methotrexate administration. Recovery has been reported with discontinuation of therapy.
10. Potentially fatal opportunistic infections, especially Pneumocystis jiroveci pneumonia, may occur with methotrexate therapy.
11. Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis.
Rasuvo is contraindicated in the following:
- Pregnancy: Rasuvo can cause fetal death or teratogenic effects when administered to a pregnant woman. Rasuvo is contraindicated in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
- Nursing Mothers: Because of the potential for serious adverse reactions from methotrexate in breast fed infants, Rasuvo is contraindicated in nursing mothers.
- Alcoholism or Liver Disease: Patients with alcoholism, alcoholic liver disease or other chronic liver disease.
- Immunodeficiency Syndromes: Patients who have overt or laboratory evidence of immunodeficiency syndromes.
- Preexisting Blood Dyscrasias: Patients who have preexisting blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia.
- Hypersensitivity: Patients with a known hypersensitivity to methotrexate. Severe hypersensitivity reactions have been observed with methotrexate use.
WARNINGS AND PRECAUTIONS
- Organ System Toxicity: Rasuvo has the potential for serious toxicity. Rasuvo should be used only by physicians whose knowledge and experience include antimetabolite therapy. Because of the possibility of severe toxic reactions (which can be fatal), Rasuvo should be used only in patients with psoriasis or rheumatoid arthritis with severe, recalcitrant, disabling disease, which is not adequately responsive to other forms of therapy.
- Embryo-Fetal Toxicity: Methotrexate has been reported to cause fetal death and/or congenital anomalies. Rasuvo is not recommended for females of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks. Rasuvo is contraindicated in pregnant women with psoriasis or rheumatoid arthritis. Exclude pregnancy before treatment. Females should be counseled on the serious risks to the fetus should they become pregnant while undergoing treatment. Avoid pregnancy if either partner is receiving Rasuvo. Advise males to avoid pregnancy for a minimum of three months after therapy and females to avoid pregnancy for at least one ovulatory cycle after therapy.
- Effects on Reproduction: Methotrexate has been reported to cause impairment of fertility, oligospermia and menstrual dysfunction in humans, during and for a short period after cessation of therapy.
- Laboratory Tests: Patients undergoing Rasuvo therapy should be closely monitored so that toxic effects are detected promptly. Baseline assessment should include a complete blood count with differential and platelet counts, hepatic enzymes, renal function tests and a chest X-ray.
- Risks from Improper Dosing: The physician and/or pharmacist should emphasize to the patient that Rasuvo is administered once weekly and mistaken daily use has led to fatal toxicity.
- Patients with Impaired Renal Function, Ascites, or Pleural Effusions: Elimination is reduced. Such patients require especially careful monitoring for toxicity and require dose reduction or, in some cases, discontinuation of Rasuvo administration.
- Dizziness and Fatigue: May impair ability to drive or operate machinery.
- Malignant Lymphomas: Non-Hodgkin’s lymphoma and other tumors have been reported in patients receiving low-dose oral methotrexate. However, there have been instances of malignant lymphoma arising during treatment with low-dose methotrexate, which have regressed completely following withdrawal of methotrexate, without requiring active anti-lymphoma treatment. Discontinue Rasuvo first and, if the lymphoma does not regress, appropriate treatment should be instituted.
- Tumor Lysis Syndrome: Like other cytotoxic drugs, methotrexate may induce “tumor lysis syndrome” in patients with rapidly growing tumors.
- Concomitant Radiation Therapy: Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis.
The most frequently reported adverse reactions include ulcerative stomatitis, leukopenia, nausea, and abdominal distress. Other frequently reported adverse reactions are malaise, undue fatigue, chills and fever, dizziness and decreased resistance to infection.
- Aspirin, NSAIDs, and Steroids: Concomitant use may elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity.
- Proton Pump Inhibitors (PPIs): Concomitant use of some PPIs may elevate and prolong serum levels of methotrexate and cause increased toxicity.
- Oral Antibiotics: Certain oral antibiotics may decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria. Use of Rasuvo with penicillins should be carefully monitored.
- Hepatotoxins: Patients receiving concomitant therapy with Rasuvo and other potential hepatotoxins should be closely monitored for possible increased risk of hepatotoxicity.
- Theophylline: Methotrexate may decrease the clearance of theophylline, therefore theophylline levels should be monitored.
- Folic Acid and Antifolates: Vitamin preparations containing folic acid or its derivatives may decrease responses to systemically administered methotrexate. Folate deficiency states may increase methotrexate toxicity.
- Mercaptopurine: Methotrexate increases the plasma levels of mercaptopurine, therefore dose adjustment may be required.
- Other Drugs: Toxicity may be increased because of displacement of certain drugs. Use of Rasuvo with probenecid should be carefully monitored.
USE IN SPECIFIC POPULATIONS
- Pediatric Use: Safety and efficacy of Rasuvo have not been established in pediatric patients with psoriasis, neoplastic disease, and pJIA.
- Geriatric Use: Use caution in dose selection. Elderly patients should be closely monitored for early signs of hepatic, bone marrow and renal toxicity.
- Renal Impairment: Elimination is reduced. Patients require careful monitoring for toxicity and require dose reduction or discontinuation of Rasuvo.
- Hepatic Impairment: Contraindicated in patients with alcoholic liver disease or other chronic liver disease.
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About Medac Pharma, Inc.
Medac Pharma, Inc. is the wholly-owned subsidiary of medac GmbH, a well-known and respected global pharmaceutical company that has been making scientific and therapeutic discoveries for more than 40 years.
Medac Pharma, Inc. is focused on developing therapies with the potential to make meaningful differences in patients’ lives. The company’s approach is to improve existing agents by enhancing the mode of delivery, addressing safety profiles and inventing ways to maximize efficacy.
For more information, please visit www.medacpharma.com.