Ortho Biotech Seeks FDA Approval For DOXIL(R) In Combination With VELCADE(R) To Treat Relapsed/Refractory Multiple Myeloma

Ortho Biotech Products, L.P., today announced that the U.S. Food and Drug Administration (FDA) has accepted an application for DOXIL(R) (doxorubicin HCl liposome injection) as combination therapy with VELCADE(R) (bortezomib) for injection to treat patients with multiple myeloma who have received at least one prior therapy.

The Supplemental New Drug Application (sNDA) is based on a planned interim analysis from the DOXIL-MMY-3001 trial, an international, multicenter, phase 3, randomized, open-label study of 646 patients with relapsed or refractory multiple myeloma who had received at least one prior line of therapy, and who were randomized to receive the DOXIL + VELCADE combination or VELCADE alone.

"We are pleased that the FDA has accepted our sNDA, as this promising combination would provide an expanded treatment option for patients with relapsed/refractory multiple myeloma," said Craig Tendler, M.D., Vice President, Clinical Affairs, Ortho Biotech.

About DOXIL

DOXIL currently is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.

IMPORTANT SAFETY INFORMATION

BOXED WARNINGS

-- Myocardial damage may lead to congestive heart failure and may be encountered as the total cumulative dose of doxorubicin HCl approaches 550mg/m2.

-- The use of DOXIL may lead to cardiac toxicity.

-- Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dose

-- Cardiac toxicity may also occur at lower cumulative doses in patients with prior mediastinal irradiation or who are receiving concurrent cyclophosphamide therapy

-- DOXIL should be administered to patients with a history of cardiovascular disease only when the potential benefit outweighs the risk

-- Cardiac function should be carefully monitored in patients treated with DOXIL

-- Acute infusion- related reactions have occurred in up to 10 percent of patients treated with DOXIL.

-- Serious and sometimes life-threatening or fatal allergic/anaphylactoid-like infusion reactions have occurred

-- Medications to treat such reactions, as well as emergency equipment should be available for immediate use

-- The majority of infusion-related events occurred during the first infusion

-- The initial rate of infusion should be 1 mg/mL to help minimize the risk of infusion reactions. (see DOSAGE AND ADMINISTRATION section in Prescribing Information)

-- Severe myelosuppression may occur

-- DOXIL dosage should be reduced in patients with impaired hepatic function (see DOSAGE AND ADMINISTRATION section in Prescribing Information)

-- Accidental substitution has resulted in severe side effects. DOXIL should not be substituted for doxorubicin on a mg per mg basis.

-- The use of DOXIL should be limited to physicians experienced with the use of cancer chemotherapeutic agents.

CONTRAINDICATIONS

-- DOXIL is contraindicated in patients who have a history of hypersensitivity reactions to a conventional formulation of doxorubicin HCl or components of DOXIL.

DOXIL IS CONTRAINDICATED IN NURSING MOTHERS.

OTHER WARNINGS

-- Hand-foot syndrome (HFS) may occur; manage with dose modifications (see DOSAGE AND ADMINISTRATION, Dose Modification Guidelines of the Prescribing Information).

-- Should extravasation occur, DOXIL is not a vesicant but should be considered an irritant (see DOSAGE and ADMINISTRATION section of the Prescribing Information).

ADVERSE EVENTS

-- The most common non-hematologic side effects (greater than or equal to 10 percent) reported with DOXIL therapy included asthenia, abdominal pain, fever, pain, mucous membrane disorder, back pain, infection, headache, nausea, stomatitis, vomiting, constipation, diarrhea, anorexia, dyspepsia, intestinal obstruction, peripheral edema, paresthesia, pharyngitis, dyspnea, cough increased, hand-foot syndrome, rash and alopecia.

DOXIL is marketed in the United States by Ortho Biotech Products, L.P., and in Israel by Janssen-Cilag. Schering-Plough Corporation, under a licensing agreement, has exclusive rights to market the medication as CAELYX(R) throughout the rest of the world, excluding Japan. For more information about DOXIL and to view the full U.S. prescribing information, including the Boxed Warnings, please visit http://www.DOXIL.com.

About VELCADE

VELCADE is the market leader in relapsed multiple myeloma with over 50,000 patients treated worldwide. Data on single agent VELCADE already demonstrate that it has been proven to extend survival of patients with previously treated multiple myeloma, providing a six-month survival advantage over patients treated with standard therapy dexamethasone.

VELCADE is being co-developed by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Millennium is responsible for commercialization of VELCADE in the U.S.; Janssen-Cilag is responsible for commercialization in Europe and the rest of the world. Janssen Pharmaceutical K.K. is responsible for commercialization in Japan. For a limited period of time, Millennium and Ortho Biotech Inc. will co-promote VELCADE in the U.S. VELCADE is approved in more than 75 countries worldwide. VELCADE also is approved in the European Union after first relapse.

VELCADE is indicated for the treatment of patients with multiple myeloma who have received at least one prior therapy. VELCADE is indicated for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic therapy.

Risks associated with VELCADE therapy include new or worsening peripheral neuropathy, hypotension observed throughout therapy, cardiac and pulmonary disorders, gastrointestinal adverse events, thrombocytopenia, neutropenia and tumor lysis syndrome. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE. Cases of severe sensory and motor peripheral neuropathy have been reported. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma. Acute development or exacerbation of congestive heart failure, and/or new onset of decreased left ventricular ejection fraction has been reported, including reports in patients with few or no risk factors for decreased left ventricular ejection fraction. There have been rare reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome in patients receiving VELCADE. Some of these events have been fatal. A higher proportion of these events have been reported in Japan. There have been rare reports of RPLS in patients receiving VELCADE. RPLS is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. VELCADE is associated with thrombocytopenia and neutropenia. There have been reports of gastrointestinal and intracerebral hemorrhage in association with VELCADE. Transfusions may be considered. Complete blood counts (CBC) should be frequently monitored during treatment with VELCADE. Rare cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions.

Safety Data:

In 1163 patients in multiple myeloma and mantle cell lymphoma studies, the most commonly reported adverse events were asthenic conditions (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheral neuropathy (39%), thrombocytopenia (36%), appetite decreased, including reports of anorexia (36%), pyrexia (34%), vomiting (33%) and anemia (29%). Twenty percent of patients reported at least one episode of grade 4 toxicity; the most common grade 4 toxicities were thrombocytopenia (5%) and neutropenia (3%). Fifty percent of patients reported serious adverse events. The most commonly reported serious adverse events were pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia (each 3%).

About Ortho Biotech Products, L.P.

Ortho Biotech Products, L.P. is a leading biopharmaceutical company devoted to helping improve the lives of patients with cancer and with anemia due to multiple causes, including chronic kidney disease. Since it was founded in 1990, Ortho Biotech and its worldwide affiliates have earned a global reputation for researching, manufacturing and marketing innovative products that enhance patients' health. Located in Bridgewater, N.J., Ortho Biotech is an established market leader in Epoetin alfa therapy for anemia management. The company also markets treatments for recurrent ovarian cancer, rejection of transplanted organs and other serious illnesses. For more information, visit http://www.orthobiotech.com.

Ortho Biotech Products, L.P.
http://www.orthobiotech.com