Status - approved; marketed

Organizations involved:

Hoffmann-La Roche Inc. – Manuf.; R&D; Tech.; World mark.

PDL Biopharma, Inc. – R&D; Tech.; World mark.

Biogen Idec, Inc. – R&D; World mark

Lonza Biologics plc – Manuf.; Tech.

National Cancer Institute – R&D; Tech.

National Institutes of Health (NIH) – Parent org.

Alusuise-Lonza Group – Parent

Seragen Inc. – Tech.; Former

Ligand Pharmaceuticals Inc. – Tech.

Celltech Biologics plc – Former

Royalty Pharma, AG – Tech.

Beth Israel Deaconess Medical Center – R&D; Tech.

University of Glasgow – Tech.

Genentech, Inc. – Tech.; Patent dispute

Cross ref.: See the entry for Monoclonal Antibodies (#300), particularly the Tech. transfer (rDNA) section. See also other interleukin-2 related products: basiliximab (Simulect; another recombinant IL-2 receptor monoclonal antibody); aldesleukin (Proleukin; recombinant IL-2); and denileukin diftitox (ONTAK; recombinant IL-2/diphtheria toxin fusion protein).

Description: Zenapax is an aqueous formulation of a recombinant humanized IgG1 monoclonal antibody (daclizumab) glycoprotein with specifically for the alpha subunit (p55 alpha; CD25; Tac subunit) of the human high-affinity interleukin-2 receptor (IL-2R) expressed on the surface of activated lymphocytes produced by a transformed murine (mouse) myeloma cell line, apparently Sp2/0 (or NS0) cells. Daclizumab is an immunoglobulin composed of human (~90%) and murine (~10%) antibody sequences, with the monoclonal antibody humanized using technology from Protein Design Labs. The human sequences were derived from the constant (framework) domains of human immunoglobulin G1 (IgG1), and the murine sequences are derived from the variable regions (active epitope-binding; complementarity determining regions or CDRs) of a murine myeloma antibody with specificity for the IL-2alpha receptor. The molecular weight of daclizumab predicted its DNA sequence is 144 kDa.

Zenapax is packaged in single-use glass vials, each containing 25 mg of daclizumab in 5 mL of a clear, sterile, colorless concentrate solution for further dilution and intravenous administration. Each mL of Zenapax contains 5 mg of daclizumab, 3.6 mg sodium phosphate monobasic monohydrate, 11 mg sodium phosphate dibasic heptahydrate, 4.6 mg sodium chloride, 0.2 mg polysorbate 80 (Tween 80), and may contain hydrochloric acid or sodium hydroxide to adjust the pH to 6.9. The product contains no preservatives. Vials should be stored at 2-8˚C (36-46˚F; refrigerated).

Nomenclature: Interleukin-2 receptor Mab, rDNA/Roche [BIO]; Zenapax [TR reg. to Roche]; daclizumab [FDA current]; dacliximab [FDA former]; immunoglobulin G1, anti-(human interleukin 2 receptor) (human-mouse monoclonal clone 1H4gamma1-chain), disulfide with human-mouse monoclonal clone 1H4 light chain, dimer [CAS]; 152923-56-3 [CAS RN]; immunoglobulin G1(human-mouse monoclonal clone 1H4gamma-chain anti-human antigen Tac), disulfide with human-mouse monoclonal clone 1H4 light chain, dimer [SY]; immunoglobulin G 1(human-mouse monoclonal clone 1H4gamma-chain anti-human interleukin 2 receptor), disulfide with human-mouse monoclonal clone 1H4 light chain, dimer [SY]; SMART anti-TAC antibody [SY]; IL-2R monoclonal antibody [SY]; Ro 24-7375 [SY]; humanized anti-Tac monoclonal antibody [SY; used by PDL]; NDC 0004-0501-09 [NDC]

Biological.: Three different types of IL-2 cellular receptors are distinguished, with each expressed differentially and independently. The high affinity IL-2 receptor (IL-2R) with Kdis =10 pM constitutes approximately 10% of all IL-2 receptors expressed by T-cells. The high-affinity IL-2R is a membrane receptor complex consisting of the two subunits IL2R-alpha (Tac antigen; T-cell activation antigen; p55) and IL2R-beta (p75; newer designation is CD122) as the ligand/receptor binding domains and a gamma chain as a signaling component. An intermediate affinity IL-2 receptor (Kdis =100 pM) consists of the IL2R-beta (p75) subunit and a gamma chain, while a low affinity receptor (Kdis =10 nM) is formed by IL2R-alpha (p55) alone. The 219 NH2-terminal amino acids of the IL2R-alpha (p55; Tac) protein, the target for binding of daclizumab, comprise an extracellular (cell surface exposed) domain (e.g., see Science, 230, 633-639, 1985).

Daclizumab functions as an IL-2 receptor antagonist by binding with high-affinity to the IL2R-alpha (Tac subunit; p55) portion of the high-affinity IL-2 receptor complex on the surface of activated T lymphocytes (T-cells), e.g., lymphocytes induced by interferon gamma, and inhibits further IL-2 binding. Daclizumab binding is highly specific for IL2R-alpha (Tac), which is expressed only on activated and not resting lymphocytes.

Administration of Zenapax inhibits IL-2-mediated activation and proliferation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection, e.g., tissue transplant rejection. While in the circulation, daclizumab acts as an immune suppressant and impairs the response of the immune system to antigenic challenges. Daclizumab and cyclosporine have complimentary mechanisms of action. Cyclosporine interferes with IL-2 production and blocks T-cell proliferative signals during early phase T-cell activation, but does not inhibit the process completely. Simulect targets IL-2 receptors, binding extensively to the receptor and blocking binding of IL-2, inhibiting IL-2-driven proliferation of activated T-cells.

Daclizumab is a recombinant “humanized” monoclonal antibody, while another product targeting the same IL-2 receptor, basiliximab (Simulect), is a recombinant “chimeric” monoclonal antibody. These semantic distinctions are made on the basis of the structures of the human and murine antibody portions combined into the immune globulin molecule and related recombinant methods; and also related technology, patents, licensing, and disputes. Humanized monoclonal antibodies generally incorporate a smaller percentage and portions of murine monoclonal antibodies than do chimeric antibodies. See the Monoclonal Antibodies entry (#300) for further information.

Companies.: Zenapax was developed by Protein Design Labs, Inc. (PDL) in collaboration with Hoffmann-La Roche Inc. Zenapax is manufactured by Hoffmann-La Roche Inc. (Nutley, NJ), FDA CBER est. lic. no. 0136. Hoffmann-La Roche has exclusive worldwide manufacturing and marketing rights, and markets Zenapax in the U.S. and other countries worldwide. The National Cancer Institute (NCI), National Institutes of Health (NIH), was considerably involved in the discovery and development of Zenapax, including licensing key patents on IL-2R-alpha (Tac) and conducting clinical trials.

On Oct. 25, 1999, PDL and Hoffmann-La Roche Inc. announced an agreement to accelerate the development of Zenapax for the treatment of autoimmune diseases (new indications:; currently in development). Roche retained exclusive worldwide rights to Zenapax for non-autoimmune diseases as well as commercialization rights worldwide, and continued to market Zenapax for prevention of kidney transplant rejection. PDL assumed worldwide responsibility and costs for the clinical development of Zenapax in autoimmune diseases. Roche supplies, at no cost to PDL, Zenapax for use in clinical testing; and PDL may purchase additional quantities. In return for undertaking clinical development, PDL receives a significant share of Zenapax revenues from sales for autoimmune indications:, including the majority of net sales for all autoimmune indications: in the U.S. and Canada. PDL assumed responsibility to market, promote, and detail Zenapax for autoimmune indications: in U.S. and Canada, and pays for these activities out of its share. Outside of the U.S. and Canada, Roche may elect to market Zenapax for autoimmune indications:, with PDL receiving a substantial portion of revenue from autoimmune indications:. For countries and indications: for which Roche elects not to market, PDL receives an exclusive license to market Zenapax and will pay Roche a small royalty.

In Sept. 2003, PDL and Roche modified their agreement concerning Zenapax development. PDL obtained exclusive worldwide rights to market, develop manufacture and sell Zenapax for all indications: other than organ transplantation, with this including asthma and related respiratory diseases; and the agreement increased PDL’s royalties on sales outside the U.S.. At the time, PDL was conducting Phase II trials for moderate-to-severe ulcerative colitis and severe asthma. PDL also obtained rights to manufacture the product. Roche continues to market Zenapax in transplantation indications: until 2007. PDL paid $80 million for return of all exclusive rights in indications: other than transplantation and a reversion right, exercisable in 2006 but effective in 2007, to repurchase all rights in remaining transplant indications:, unless earlier elected by Roche. Transfer of Zenapax transplantation indications: to PDL will result in an additional exercise fee based on recent sales payable to Roche (e.g., about $21 million based on 2003 sales). If PDL does not receive transplantation rights, PDL would pay modest royalties to Roche on any sales in diseases other than transplantation, and would continue to receive royalties on sales of Zenapax sold by Roche in transplantation.

In fall 1993, Roche concluded a long-term manufacturing agreement with Celltech Group plc, later Celltech Biologics plc, now Lonza Biologics plc, a subsidiary of Alusuise-Lonza Group, for production and supply of daclizumab. However, FDA records indicate the marketed product is solely manufactured by Roche in its own facilities (but CBER records are often unreliable, incomplete or ambiguous regarding contract manufacturing).

Based on a Jan. 2003 CIBC World Markets Report on PDL, the company has been receiving royalties of 12% of sales from Roche.

In Sept. 2004, PDL and Roche again modified their agreement concerning co-development and and marketing of Zenapax worldwide for asthma and related respiratory disease indications:. PDL received a $17.5 million upfront payment, and is eligible for $187.5 million in milestone payments. Development costs will be shared, and both companies will co-promote the product in the U.S. PDL will receive royalties on sales for asthma outside the U.S. This agreement was prompted by positive Phase II results from a PDL trial in which Zenapax significantly improved FEV1 scores in moderate to severe asthma patients. As per the prior agreement, PDL will have the option to re-acquire the transplantation rights as well in 2007.

In Aug. 2005, PDL concluded an agreement with Biogen Idec Inc. for development of three PDL monoclonal antibodies: daclizumab (Zenapax), volociximab (M200) and fontolizumab (HuZAF). Biogen Idec is developing daclizumab for multiple sclerosis (MS). The agreement includes development of PDL’s daclizumab for indications: other than transplant and respiratory diseases, which had been licensed to Roche, and kidney transplant rejection. At the time, daclizumab was in Phase II trials for MS. As part of the overall agreement, Biogen Idec paid PDL $40 million up front and purchased $100 million of stock; and PDLI is eligible for up to $660 million in milestones. In the U.S. and EU, the companies will co-promote resulting products and will split development costs and operating profits. In other territories, Biogen Idec will fund development and commercialization and pay royalties to PDL.

In Nov. 2005, PDL expanded its agreement with Roche to include the co-development of a subcutaneous version of daclizumab for long-term transplant maintenance therapy (with the product currently administered by intravenous injection and marketed by Roche for induction transplant therapy). PDL received a $10 million upfront payment and is eligible for up to $145 million in milestones. PDL and Roche share development costs, and PDL has the option to co-promote subcutaneous daclizumab for transplant maintenance in the U.S. PDL will receive royalties on Roche’s sales outside the U.S.

In Aug. 2006, Roche dissolved its agreement with PDL Biopharm to develop and market daclizumab for asthma indications:, which both companies had been co-developing since 2004, leaving PDL with exclusive rights. PDL reported it was seeking new partner for daclizumab development (for this indication).

In Nov. 2006, Roche dissolved its agreement with PDL Biopharm to develop and market daclizumab for organ transplant patients on longer-term maintenance therapy, leaving PDL with exclusive rights. The co-development agreement between PDL and Roche formally terminated in May 2007. PDL is continuing its development of daclizumab for relapsing/remitting multiple sclerosis, with results from the ongoing Phase 2 CHOICE study of daclizumab in combination with beta-interferon expected later in 2007. PDL is reportely seeking a new partner(s) for daclizumab development (for this indication).

In spring 2007, the collaboration of Biogen Idec, Inc. and PDL was continuing development of daclizumab in multiple sclerosis (MS) and indications: other than transplant and respiratory diseases.

Manufacture: The sequence of the Eu human antibody was used to provide the framework of the humanized antibody, because the amino acid sequence of the heavy chain variable region of the IL2R-alpha (Tac) antibody shares considerable homology with the heavy chain of this antibody. Plasmid pHuLTAC contains the complete humanized light chain and plasmid pHuGTAC1 contains the complete heavy chain of daclizumab. Both plasmids (co)express high levels of their respective glycoproteins when transfected into mouse Sp2/0 cells, producing dimeric daclizumab antibody.

Manufacture of daclizumab presumably entails use of the glutamine synthetase (GS) recombinant mammalian cell vector selection, amplification, and expression system licensed from Celltech Biologics plc, now Lonza Biologics plc, a subsidiary of Alusuise-Lonza Group, which receives unspecified royalties from Novartis on sales of Simulect. The technology is coassigned to the University of Glasgow, which presumably also receives royalties. The Lonza GS technology involves dominant selectable markers for use in co-amplification of non-selected genes and in transforming host cell lines to glutamine independence. See related patents including U.S. 5,770,359 and 5,747,308. The glutamine synthetase gene is used in recombinant vectors as a marker along with another gene(s), with only successfully transformed NS0 cells (normally deficient in glutamine synthetase) being capable of producing their own GS and surviving in glutamine-deficient culture media. Over 40 companies have licensed GS System technology for various uses.

FDA class: Biologic BLA

CBER class: Biological Response Modifiers

CBER to CDER: Among the products transferred within FDA on June 30, 2003

Approvals: Date = 19971210; first approval, BLA; orphan designation (granted 3/5/1993, expires 12/10/2004)

Date = 20020729; BLA supplement; Indication = include pediatric use and update the Clinical Pharmacology, Clinical Studies, and Adverse Reactions sections of the package insert with three year post-transplant data

Indications: [full text of “INDICATION AND USAGE” section of product insert/labeling]:

ZENAPAX is indicated for the prophylaxis of acute organ rejection in patients receiving renal transplants. It is used as part of an immunosuppressive regimen that includes cyclosporine and corticosteroids.

Status: The BLA for Zenapax was submitted on June 10, 1997, received priority review, and was approved on Dec. 10, 1997 with orphan designation; review time of six months (.50 year).

European Union approval of Zenapax was granted on Feb. 26, 1999 for the prevention of acute organ rejection in patients receiving kidney transplants.

Tech. transfer: Hoffmann-La Roche Ltd. obtained a nonexclusive license in September 1999 from Seragen Inc., now Ligand Pharmaceuticals, for the “Strom” patents covering the use of IL-2 receptor antibodies for treatment of rejection and autoimmune diseases. The license covers sale by Roche of Zenapax in the U.S., Canada, Australia and New Zealand. Seragen received $2.5 million for royalties on sales prior to the licensing. Seragen receives unspecified royalties starting Jan. 2001, and is eligible for milestone payments if Zenapax receives approval in the U.S. for treatment of autoimmune diseases. Seragen had originally exclusively licensed the Strom patents from Beth Israel Deaconess Medical Center (Boston, MA), which receives a share of royalties from sublicensees.

In late 1999, Ligand sold its rights to royalties from Roche’s sales of Zenapax (and also Novartis’ sales of Simulect) starting Jan. 2001 to Pharmaceutical Partners, now Royalty Pharma, AG, for $3.25 million plus up to $3.25 million more depending on sales in 2001-2004.

Protein Design Labs. (PDL) nonexclusively licensed technology from the National Cancer Institute (NCI), National Institutes of Health (NIH), lic. no. L-057-89. This included U.S. 6,113,900, "Use of IL-2 receptor-targeted therapeutics to inhibit allograft rejection and treat autoimmune disorders," expired Sept. 5, 2005, concerning conjugated and unconjugated interleukin-2 receptor (IL-2R) Tac ( IL2R-alpha; T-cell activation antigen; p55) useful for treatment of graft-versus-host disease, leukemia, autoimmune diseases, allograft rejection and other disorders mediated by Tac-expressing adult T-cells or involving abnormal IL-2R expression, and (IL-2R) Tac monoclonal antibodies (e.g., daclizumab).

Recombinant monoclonal antibody humanization technology has been nonexclusively licensed by Hoffmann-La Roche from Protein Design Labs. (PDL), and PDL performed humanization of daclizumab. See the Tech. transfer (rDNA) section of the Monoclonal Antibodies entry (#300) for further information about the complex patent, licensing, cross-licensing, and patent disputes concerning recombinant chimeric/humanized monoclonal antibodies. This includes long-running monoclonal antibody humanization patent disputes between PDL and Genentech. Currently, Genentech holds a very strong position in U.S recombinant chimeric/humanized monoclonal patents with its “New Cabilly” patent and cross-licensing with Celltech. Daclizumab was the first monoclonal antibody humanized by PDL to reach the market. With Roche the majority owner of Genentech, it presumably has licensed Genentech’s patents.

In April 2007, the Opposition Division of the European Patent Office uphold PDL’s claims in European Patent 0 451 216 (‘216 patent), filed in Oct. 1991, expired 2011, covering the production of humanized antibody light chains that contain amino acid substitutions made under PDL’s antibody humanization technology, and provides specific coverage for daclizumab. The patent had been disputed by up to 18 other parties at one point, but Genentech and four other companies had already withdrawn their opposition by the time of the decision.

Trials: In the pivotal Phase III trial involving 260 patients, after six months, 35% of conventionally-treated patients who did not receive Zenapax showed signs of kidney rejection compared to 22% of conventionally-treated patients who also received Zenapax. All patients received cyclosporine, corticosteroids and azathioprine, the standard triple-therapy immunosuppressive regimen for kidney transplant patients. Patients receiving such immunosuppressive treatments following organ transplantation are at increased risk for developing infections and lymphomas. Patients treated with daclizumab did not have more infections or other immune disorders than those in the control group. Studies are continuing to assess the long-term effects of Zenapax on the immune system.

Protein Design Labs. (PDL) halted development of Zenapax for maintenance of remission in psoriasis patients in early 2002 after failure to meet the primary endpoint in a Phase II trial. Zenapax also failed in Phase II/III trials conducted by Roche for graft-vs.-host disease. Roche is conducted Phase III trials for prevention of rejection in heart transplants.

In March 2004, PDL reported positive results from a trial in 114 patients with chronic persistent asthma whose disease was not well controlled with high doses of inhaled corticosteroid therapy. The trial met its primary endpoint, a significant (p=0.05) percent change in FEV1 from baseline to 12 weeks (day 84). Secondary clinical endpoints also supported these findings. PDL reported that its next trial of Zenapax in asthma would be a trial with subcutaneous administration.

In spring 2005, PDL began a single-dose Phase I study of daclizumab administered subcutaneously for treatment of asthma. This will be followed by a multiple-dose study in healthy volunteers expected to be initiated in the summer 2005. A Phase II dose range-finding study of subcutaneously administration in asthma patients was planned for first quarter 2006. These trials are using antibody manufactured by PDL.

Positive results were also reported from a Phase Ib trial of Zenapax plus Betaseron (interferon beta-1b) in multiple sclerosis patients in spring 2004. A randomized, placebo-controlled, Phase II study of daclizumab in 270 patients with multiple sclerosis started in second quarter 2005. Patients with active relapsing forms of MS are receiving subcutaneous daclizumab at one of two dosage levels, or placebo, for six months in addition to their current beta-interferon treatment.

In May 2004, PDL reported that Zenapax did not meet the primary endpoint in a Phase II clinical trial for moderate or severe ulcerative colitis. The primary efficacy endpoint, the proportion of patients who achieved remission at week eight, did not meet statistical significance at either of the dose levels tested. PDL reported it was abandoning development of Zenapax for this indication, and will concentrate on development of a new monoclonal antibody, Nuvion, which has shown promise in Phase I trials for treatment of severe ulcerative colitis. Zenapax’s failure for this and other indications: may be related to its lack of ability to induce apoptosis (which Nuvion does).

PDL trials had shown promise for uveitis, but the company never initiated Phase III studies due to the small market for this indication. However, a Phase III trial for uveitis sponsored by the National Eye Institute began in 2002.

In Oct. 2007, PDL and Biogen Idec reported that the ongoing Phase II, randomized, double-blind, placebo-controlled CHOICE trial of daclizumab met its primary endpoint in 230 relapsing multiple sclerosis (MS) patients being treated with interferon beta. Patients randomly receive daclizumab 2 mg/kg every two weeks, daclizumab 1 mg/kg every four weeks or placebo added to ongoing interferon beta treatment. Patients from the CHOICE study were followed for an additional 48 weeks after the daclizumab treatment period to further assess safety and efficacy. The primary efficacy analysis showed that at 24 weeks, the 75 patients in the 2 mg/kg group experienced 72% fewer new or enlarged gadolinium-enhancing lesions (Gd+) on average compared to the 77 patients who received a placebo (p=0.004). The 78 patients in the 1 mg/kg group experienced a 25% reduction in new or enlarged lesions compared with placebo, but that measurement did not achieve statistical significance. Based on data up to week 24, analysis of the relapse rate, which was a secondary endpoint, indicates that both daclizumab regimens revealed a trend in reducing the annualized relapse rate compared to placebo (an approximately 35% reduction), but these observations did not reach statistical significance. Preliminary safety data showed similar rates of infection across all treatment groups with an overall greater incidence of serious infections in the daclizumab treated groups. (4.6% vs. 1.3% placebo). With these positive results, PDL inititated the SELECT trial of daclizumab as a single agent in patients with relapsing MS.

PDL also continues to evaluate the opportunity to develop daclizumab further in the setting of solid organ transplantation.

In Sept. 2010, Biogen Idec and Abbott initated a global Phase III study evaluating the efficacy and safety of daclizumab compared to interferon beta-1a (Avonex; see related entry) in patients with relapsing-remitting multiple sclerosis (RRMS), the most common form of multiple sclerosis (MS). The trial, DECIDE, used a subcutaneous formulation of daclizumab intended for monthly administration. DECIDE ws a global Phase III, randomized, double-blind, active-comparator study expected to enroll approximately 1,500 RRMS patients in 28 countries. Under the terms of their collaboration agreement, Biogen Idec made a $30 million milestone payment to Abbott, due upon enrollment of the first patient in the DECIDE trial.

Medical: The recommended dose for Zenapax is 1.0 mg/kg. Based on clinical trials, the standard course is five doses. The first dose should be given no more than 24 hours before transplantation. The four other doses should be given at intervals of 14 days, with a course of treatment involving 10 weeks. The calculated volume of Zenapax is mixed with 50 mL of sterile 0.9% sodium chloride solution and administered via a peripheral or central vein over a 15-minute period. Daclizumab specifically blocks IL-2 receptor, inhibiting IL-2-driven proliferation of activated T-cells and reducing acute tissue rejection.

Zenapax is used in combination with cyclosporine A and steroids for immunosuppressive therapy in renal transplant patients. Sandoz Ltd., now Novartis AG, markets cyclosporine (which is now also available in generic formulations), and is the world’s leader in rejection therapeutics (including also marketing Simulect).

For long-term maintenance therapy in transplant patients, most currently receive a combination of Roche’s CellCept (mycophenolate mofetil) with a calcineurin inhibitor, such as cyclosporine and steroids, to prevent organ rejection. However, long- term use of the current calcineurin inhibitors can cause kidney toxicity, diabetes and cardiovascular disorders. Subcutaneous daclizumab as maintenance treatment in combination with CellCept may allow for the reduction and potential elimination of more toxic drugs from transplant maintenance regimens.

Disease: The potential market for relapsing-remitting MS is about 350,000 patients in the U.S. and 160,000 in Europe. The potential market for daclizumab for asthma could dwarf that for organ transplantation and multiple sclerosis. PDl estimates there are 5.2 million patients with moderate to severe asthma in the U.S., 7 million in Europe and 1.5 million in Japan.

PDL expects to concentrate development on acute hospital-based treatment of asthma, positioning Zenapx as a required product in emergency rooms. About 10,000 people die annually in the hospital from acute asthma.

Market: Zenapax sales have not been reported in recent years (which generally indicates sales are low). The author’s rough/crude guess for 2006 sales is in the range of $40-$60 million. Total Zenapax sales were $33 million in 2003, and sales were steady in the $30-35 million range for several years before this. Analysts had originally projected a $100 million market for Zenapax’s currently approved indication (use with cyclosporine for organ transplantation), sales never attained this level. Total 2005 sales of Zenapax were projected by Cayuga MBA Fund LLC to be in the range of $150-$200 million.

The 2007 Average Wholesale Price (AWP) is $493.34/5 mg/mL, 5 ml (25 mg) vial (Red Book, 2007).

In Jan. 2004, the U.K. National Institute for Clinical Excellence (NICE), which provides guidelines for purchase and use of pharmaceuticals by the National Health Service (NHS), issued a final appraisal of Zenapax and Simulect, recommending both products for induction therapy in the prophylaxis of acute organ rejection in patients undergoing renal transplantation (and that the cheapest recommended product be used). R&D: Biogen Idec is developing Daclizumab high-yield process (DAC HYP), a subcutaneous formulation of daclizumab for the treatment of RRMS. Positive Phase III trial results were repoted in Aug. 2011.