NUTLEY, N.J. and FREMONT, Calif., Nov. 1 /PRNewswire-FirstCall/ -- Roche
and Protein Design Labs, Inc. (PDL) (Nasdaq: PDLI) today announced an
expansion to their partnership to co-develop and commercialize daclizumab for
organ transplant patients on long-term, maintenance therapy. Roche currently
markets daclizumab for induction transplant therapy as Zenapax(R). Roche and
PDL are developing a new subcutaneous daclizumab (daclizumab s.c.)
formulation, manufactured by PDL, for use in Phase II clinical trials expected
to start in 2006.
Currently, transplant patients are treated with the combination therapy of
Roche's CellCept(R) (mycophenolate mofetil) with a calcineurin inhibitor such
as cyclosporine and steroids to prevent organ rejection. However, the long-
term use of the current calcineurin inhibitors can cause kidney toxicity,
diabetes and cardiovascular disorders. Using daclizumab s.c. as maintenance
treatment in combination with CellCept may allow for the reduction, and
potential elimination, of the more toxic drugs from transplant patient
maintenance regimens.
Mark McDade, Chief Executive Officer, PDL, said, "We are enthusiastic
about the opportunity to develop daclizumab s.c. with our longstanding partner
Roche. Today's agreement builds upon our existing collaboration with Roche in
asthma, as we continue to explore development of daclizumab s.c. in other
indications."
"Roche and PDL are highly committed to daclizumab, our partnership, and in
developing better treatments to improve long-term outcomes for transplant
patients," said Peter Hug, Roche's Global Head of Pharma Partnering. "With
the potential to use CellCept(R) and daclizumab s.c. as the centerpiece for
long-term transplant therapy, we could offer patients a safer, more tolerable
option."
Roche and PDL have amended their current agreements to reflect the scope
of daclizumab s.c.'s further development. Under the terms of this agreement,
PDL will receive a $10 million upfront payment and may be eligible to receive
payments up to $145 million if certain milestones are satisfied and if the
indication is successfully developed. Roche will continue to manufacture and
promote Zenapax(R) exclusively on a worldwide basis. Roche and PDL will share
equally global development costs, and PDL has the option to co-promote
daclizumab s.c. for transplant maintenance in the United States. Outside the
United States, PDL will receive royalties on net sales of the product in
transplant maintenance. As part of this arrangement, the parties agree that
PDL will not exercise its option to promote Zenapax(R) for prevention of acute
kidney transplant rejection and PDL is no longer required to make the payment
which would otherwise be due in 2007 for such right. PDL and Roche will
continue with the co-development of daclizumab s.c. in respiratory disorders,
as announced in September 2004.
About the Roche - PDL partnership
In 1989, Roche acquired the worldwide rights to daclizumab, a product
approved in 1997 as Zenapax(R) for the prevention of renal allograft
rejection. In October 2003, Roche returned to PDL all rights to daclizumab,
except in transplantation where PDL retained the option until 2007 to re-
acquire development rights. In September 2004, PDL and Roche announced the
continued co-development of daclizumab s.c. in respiratory disorders.
Roche in Transplantation
Roche is strongly committed to improving the long-term outcomes of
transplantation and enhancing the quality of life of transplant recipients.
Roche has developed innovative therapies that improve graft and post-
transplant health. CellCept is the cornerstone of current immunosuppressant
therapies for transplant recipients and is the largest selling branded
immunosuppressive in North America. Zenapax(R) prevents acute rejection of the
newly transplanted organ. Valcyte(R) (valganciclovir) was developed for the
prevention of cytomegalovirus, a dangerous viral infection associated with
transplantation. In addition, Roche supports basic research in transplantation
with its funding of the independent Roche Organ Transplantation Research Fund
(ROTRF), which directly supports innovative research projects attracting new
researchers with innovative and novel scientific ideas to meet unmet medical
needs in solid organ transplantation.
About Protein Design Labs
PDL is a biopharmaceutical company focused on the research, development
and commercialization of novel therapies for inflammation and autoimmune
diseases, acute cardiac conditions and cancer. PDL markets several products
in the United States through its hospital sales force and wholly-owned
subsidiary, ESP Pharma, Inc. As a leader in the development of humanized
antibodies, PDL has licensed its patents to numerous pharmaceutical and
biotechnology companies, some of which are now paying royalties on net sales
of licensed products. Further information on PDL is available at http://www.pdl.com.
About Roche - More Than a Century in the U.S. and the World
Founded in 1896 and headquartered in Basel, Switzerland, Roche is one of
the world's leading innovation-driven healthcare groups. Its core businesses
are pharmaceuticals and diagnostics. Roche is one of the world's leaders in
diagnostics, the leading supplier of pharmaceuticals for cancer, as well as a
leader in virology and transplantation. As a supplier of products and
services for the prevention, diagnosis and treatment of disease, the Group
contributes on many fronts to improve people's health and quality of life.
Roche employs roughly 65,000 people in 150 countries, including approximately
15,000 in the United States.
For further information, please visit our worldwide and U.S. website
(Global: http://www.roche.com and U.S.: http://www.roche.us).
Facts About Zenapax, CellCept and Valcyte
Zenapax is a humanized monoclonal antibody that blocks interleukin-2 (IL-
2) receptors and acts as an immunosuppressant. It is used just before and/or
at the time of kidney transplantation in combination with cyclosporine and
corticosteroids to prevent early rejection. The recommended dose of Zenapax is
1.0 mg/kg. Based on clinical trials, the standard course of Zenapax therapy is
five doses. Zenapax received U.S. Food and Drug Administration (FDA) approval
in December 1997.
The most frequently reported adverse events associated with Zenapax were
constipation, nausea, diarrhea and vomiting. Cellulitis and wound infections
occurred more frequently in patients treated with Zenapax versus placebo.
Severe hypersensitivity reactions following Zenapax administration have been
reported rarely. Only physicians experienced in immunosuppressive therapy and
management of organ transplant patients should prescribe Zenapax. The
physician responsible for Zenapax administration should have complete
information requisite for the follow-up of the patient.
CellCept is an immunosuppressant or anti-rejection drug approved for use
in combination with other immunosuppressive drugs (cyclosporine and
corticosteroids) for the prevention of rejection in patients receiving kidney,
heart and liver transplants.
There are no adequate and well-controlled studies in pregnant women. As
CellCept (mycophenolate mofetil) has been shown to have teratogenic effects in
animals at subclinical doses on a body surface area basis, it may cause fetal
harm when administered to a pregnant woman. CellCept should not be used in
pregnant women unless the potential benefit justifies the potential risk to
the fetus. Women of childbearing potential should have a negative serum or
urine pregnancy test with a sensitivity of at least 50 mIU/mL within one week
prior to beginning therapy even where there has been a history of infertility,
unless due to hysterectomy.
Women of childbearing potential must use effective contraception before
beginning CellCept therapy, during therapy and for six weeks following
discontinuation of therapy. Two reliable forms of contraception must be used
simultaneously unless abstinence is the chosen method. If pregnancy occurs
during treatment, the physician and patient should discuss the desirability of
continuing the pregnancy (see complete product information).
Adverse events reported in >30% of renal, cardiac or liver transplant
patients receiving CellCept (in combination with cyclosporine and
corticosteroids) were pain, fever, headache, asthenia, anemia, leucopenia
(patients should be monitored for neutropenia; dosing should be interrupted or
the dose reduced if neutropenia develops), thrombocytopenia, leukocytosis,
urinary tract infection, hypertension, hypotension, peripheral edema,
hypercholesteremia, hypokalemia, hyperglycemia, creatinine, BUN and cough
increased, hypomagnesemia, diarrhea, constipation, nausea, vomiting,
respiratory infection, dyspnea, lung disorder, pleural effusion, tremor and
insomnia.
Patients receiving immunosuppressant regimens are at increased risk of
developing lymphomas and other malignancies, particularly of the skin.
Warning: Increased susceptibility to infection and the possible
development of lymphoma may result from immunosuppression. Only physicians
experienced in immunosuppressive therapy and management of renal, cardiac or
hepatic transplant patients should use CellCept. Patients receiving the drug
should be managed in facilities equipped and staffed with adequate laboratory
and supportive medical resources. The physician responsible for maintenance
therapy should have complete information requisite for the follow-up of the
patient.
Valcyte, the oral pro-drug of Cytovene (ganciclovir), is the most widely
prescribed anti-CMV medication in the United States. Valcyte is indicated for
the prevention of CMV disease in kidney, kidney-pancreas and heart transplant
patients at high risk. Valcyte is not approved for use in liver
transplantation. The efficacy and safety of Valcyte in other solid organ
transplants, such as lung transplant, have not been established.
The clinical toxicity of Valcyte, which is metabolized to ganciclovir,
includes granulocytopenia, anemia and thrombocytopenia. In animal studies
ganciclovir was carcinogenic, teratogenic and caused aspermatogenesis. Valcyte
tablets should not be administered if the absolute neutrophil count is less
than 500 cells/uL, the platelet count is less than 25,000/uL or the hemoglobin
is less than 8 g/dL. Severe leukopenia, neutropenia, anemia,
thrombocytopenia, pancytopenia, bone marrow depression and aplastic anemia
have been observed in patients treated with Valcyte tablets (and ganciclovir).
Other adverse events reported with a frequency of greater than or equal to 5%
included diarrhea, tremors, fever, nausea, headache, vomiting, insomnia and
allograft rejection.
In liver transplant patients, there was a significantly higher incidence
of tissue-invasive CMV disease in the Valcyte-treated group compared with the
oral ganciclovir group (see CLINICAL TRIALS in the complete product
information).
For full prescribing information on CellCept, Zenapax and Valcyte, please
visit: http://www.rocheusa.com/products/transplantation.html
SOURCE Protein Design Labs, Inc.
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Related links:
http://www.pdl.com
CONTACT:
Maureen Byrne of Roche, +1-973-562-2203, or
maureen.byrne@roche.com; or James R. Goff of PDL,
+1-510-574-1421, or jgoff@pdl.com
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