Status - approved in U.S. in April 2009; approved in EU in Oct. 2009

Organizations involved:

Centocor Inc. – Manuf.; R&D; Tech.; USA mark.

Johnson & Johnson – Parent

Medarex Inc. - R&D; Tech.

Schering-Plough Corp. – Former

Merck & Co., Inc. – Intl. mark.; Parent

Gallus Biopharmaceuticals, LLC – Manuf.

Mitsubishi Tanabe – Japan mark.

Bayer AG – Patent dispute

New York University (NYU) – Tech.

Abbott Labs. – Patent dispute

OXO International, Ltd. – Tech.

Cross ref.: See the entries for the other tumor necrosis inhibitor products – etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira) and Cimzia.

Description: Simponi is an aqueous formulation of golimumab, a fully human recombinant IgG1kappa tumor necrosis factor alpha (TNF-alpha) monoclonal antibody. Golimumab exhibits multiple glycoforms with molecular masses of approximately 150 to 151 kDa. Golimumab was generated using genetically engineered mice immunized with human TNF, resulting in an antibody with human-derived antibody variable and constant regions. Golimumab is produced by a recombinant cell line [no further information disclosed in product labeling] cultured by continuous perfusion and is purified by a series of steps that includes measures to inactivate and remove viruses.

Simponi does not contain preservatives. Simponi is provided as 50 mg of the golimumab antibody in 0.5 mL of solution. Each 0.5 mL of Simponi contains 50 mg of the golimumab antibody, 0.44 mg of L-histidine and L-histidine monohydrochloride monohydrate, 20.5 mg of sorbitol, 0.08 mg of polysorbate 80 (Tween 80), and Water for Injection. Simponi is stored refrigerated at 2ºC to 8ºC (36ºF to 46ºF).

Centocor/J&J has disclosed negligible information about the manufacture or other biotechnology aspects of Golimumab. Centocor manufactured golimumab by continuous perfusion . It may be presumed that the product is manufactured using transformed Chinese hamster ovary (CHO) or another mammalian cell line, most likely incorporating recent technologies allowing high(er) expression and purification yields.

Simponi is administered by 50 mg subcutaneous injection once a month. Patients can choose Simpoini packaged in the single dose SmartJect autoinjector (NDC 57894-070-02) or the single dose prefilled glass syringe (NDC 57894-070-01). Each single dose SmartJect autoinjector contains a prefilled glass syringe (27 gauge inch) providing 50 mg of Simponi per 0.5 mL of solution. The SmartJect autoinjector used with Simponi is designed so patients do not ever have to see the needle. It has an activation button on the side, and it takes just a simple squeeze to inject. The easy-to-grip, oval-shaped body fits comfortably in the patient’s hand. It has a safety sleeve to make sure the patient injects their medicine only when firmly pressed against the skin.

For patients who prefer to use a prefilled syringe, Simponi gives them this choice too. Each single dose prefilled glass syringe (27 gauge inch) contains 50 mg of Simponi per 0.5 mL of solution.

In the European Union, Simponi is available in two device forms, either through the SmartJect autoinjector designed to meet the needs of arthritis patients or as a prefilled syringe.

Nomenclature: TNF Mab, rDNA, human/J&J [BIO]; Simponi [TR U.S.]; Golimumab [USAN; INN]; immunoglobulinG1, anti-(human tumor necrosis factora) (human monoclonal CNTO148 g1-chain), disulfide with human monoclonal CNTO148 kchain), dimer [CAS]; 476181-74-5 [CAS RN]; GenTNV 148.26.12 [SY]; NDC 57894-070-01 and NDC 57894-070-02 [NDC]

Biological.: Golimumab is a human monoclonal antibody that binds to both the soluble and transmembrane bioactive forms of human TNF-alpha. This interaction prevents the binding of TNF-alpha to its receptors, thereby inhibiting the biological activity of TNF-alpha (a cytokine protein). There was no evidence of the golimumab antibody binding to other TNF superfamily ligands. Golimumab antibody does not bind or neutralize human lymphotoxin. Golimumab does not lyse human monocytes expressing transmembrane TNF in the presence of complement or effector cells. In clinical studies, decreases in C-reactive protein (CRP), interleukin (IL)-6, matrix metalloproteinase 3 (MMP-3), intercellular adhesion molecule (ICAM)-1 and vascular endothelial growth factor (VEGF) were observed following administration in patients.

Medarex used its UltiMAb Human Antibody Development System to design Golimumab. UltiMAb includes (i) HuMAb-Mouse technology developed by Medarex, (ii) Kirin's TC Mouse technology, and (iii) the KM-Mouse technology, a crossbred mouse that combines the characteristics of the HuMAb-Mouse with Kirin's TC Mouse. The transgenic mice can be inoculated with an antigen to develop fully-human, mouse-derived recombinant antibodies. Golimumab appears to have been designed solely or primarily using HuMAb-Mouse technology. Because the human genes in the HuMAb-Mouse are stable, they are passed on to offspring of the mice. Mice can be bred indefinitely at relatively low cost and without additional genetic engineering. HuMAb-Mouse can generate fully human antibodies with affinities in the picomolar range, as high as 1012.

UltiMAb can create all types of antibodies that are fully human (100% human protein sequences) by using transgenic mice in which mouse antibody gene expression is suppressed and effectively replaced with human antibody gene expression. Because these mice contain genes encoding human antibodies, the monoclonal antibodies generated are more likely to have favorable safety profiles and be eliminated less rapidly from the human body, potentially reducing the frequency and amount of dosing required.

As a fully human recombinant TNF antibody, Golimumab is similar to Adalimumab from Abbott (see related entry above), and may have advantages, e.g., lower immunogenicity, compared to other TNF Mabs, e.g., chimeric antibodies such as infliximab (Remicade). Compared to other marketed TNF Mabs, Golimumab is claimed to offer greater affinity and specificity in targeting and controlling TNF alpha.

Long-term animal studies of golimumab have not been conducted to evaluate its carcinogenic potential. Mutagenicity studies have not been conducted with golimumab. A fertility study conducted in mice using an analogous anti-mouse TNF-alpha antibody showed no impairment of fertility.

Companies.: Simponi was developed and is manufactured and marketed by Centocor Ortho Biotech, CBER/FDA est. no. 1821, a subsidiary of Johnson & Johnson (J&J). It is marketed in the U.S., Japan and certain Asian countries by Centocor and related J&J companies; and in other countries by Schering-Plough, which was acquired by Merck & Co., Inc. in March 2009.

Manufacture was performed at Centocor facilities in St. Louis, MO (acquired by Gallus Biopharmaceuticals, a CMO, in May 2011). Gallus has continued as a contract manufacturer for J&J.

Golimumab was originally developed by Medarex using its UltiMAb Human Antibody Development System. Medarex designed and conducted early development with golimumab, licensed the product to Centrocor for further development, receives development milestone payments, and will receive royalties on sales reported to be in the 3-5% range.

In 1998, Centocor concluded an agreement with Schering-Plough, granting the company the option to market Golimumab in most international territories (outside of the U.S., Japan and certain Asian countries), including Europe. In 2005, Schering-Plough exercised this option. Mitsubishi Tanabe has marketing rights in Japan. [Remicade, like CNTO-148, was originally developed by Centocor, and is exclusively marketed in the U.S. by Centocor/J&J and by Schering-Plough in most international markets (except Japan). Thus, in nearly all markets worldwide, CNTO-148 will be marketed by Centocor/J&J or Schering-Plough, the same companies also marketing Remicade]. In March 2009, Merck & Co. acquired Schering-Plough and assumed international marketing rights.

In Dec. 2007, Centocor, Inc. and Schering-Plough Corp. (now Merck) revised their 1998 distribution agreement regarding the development, commercialization and distribution of golimumab and also earlierr generation both infliximab (Remicade). Effective upon approval of golimumab in the EU, the revised agreement will extend the duration of Schering-Plough's rights to exclusively market Remicade in its current marketing territories outside the U.S. beyond 2014 to match the current duration of its exclusive marketing rights for golimumab. Schering-Plough's (Merck's) marketing rights to both products will now extend for 15 years after the first golimumab commercial sale. Centocor will receive a progressively increased share of profits on Schering-Plough's distribution of both products in Schering-Plough's territory between 2010 and 2014, remaining fixed thereafter for the remainder of the term.The revised agreement will also allow Schering-Plough to independently develop and market golimumab for Crohn's disease indications: in its territories, with an option for Centocor to participate in the program. The parties also agreed to utilize an autoinjector device developed by Centocor affiliate Cilag GmbH International in the commercialization of golimumab in their respective territories and agreed to share the autoinjector development costs. The autoinjector would allow patients to self-administer golimumab subcutaneously. The revised agreement provided for Schering-Plough to make an upfront payment of $20.5 million in the 2007 fourth quarter for rights to the autoinjector device.

In May 2009, with Schering-Plough merging into Merck, Centocor/J&J reported it was seeking arbitration to end its marketing agreement with Schering-Plough (and also for Remicade).

In April 2011, Johnson & Johnson provided additional information on its amended agreement with Merck regarding distribution rights for Remicade (and Simponi) in markets outside the United States. The amended agreement concluded the arbitration, which had been filed by J&J in May 2009; and uncertainty related to Merck had tended to depress its share price in the prior year. The deal doesn’t affect the U.S., where J&J retains exclusive rights to the two products. Merck will keep exclusive marketing rights in 70 percent of the areas where it now sells the Remicade/Simponi while J&J’s share of profit from those sales rises to 50 percent. In areas where Merck is keeping rights, J&J will get an equal share of profits starting July 1, up from the 42 percent it previously received. Merck will relinquish exclusive marketing rights to the drugs in Canada, Central and South America, the Middle East, Africa and the Asia-Pacific area starting July 1, while keeping rights in Europe, Russia and Turkey. The division of contribution income on sales was amended to a 50 percent/50 percent split between Johnson & Johnson and Merck, from July 1, 2011, through Oct. 1, 2024. Johnson & Johnson will begin recording 2011 sales of product from the relinquished territories on July 1, 2011. Johnson & Johnson will receive a one-time, $500 million payment from Merck during the second quarter of 2011. Manufacture: Mice modified to express human IgG transgenes were used for hybridoma generation. The transgenic mice were immunized with recombinant human TNF, yielding 12 hybridoma cell lines secreting human mAbs that bound human TNF with high affinity.

An F2 hybrid mouse (CBA/J x C57BL/6J), containing human variable and constant region antibody transgenes for both heavy and light chains (HuMab-Mouse; Medarex, Princeton, NJ), was immunized with 100 µg of recombinant human TNF emulsified in an equal volume of TiterMax Gold adjuvant on days 0, 12 and 28. The mouse was rested for 7 weeks, and then a final i.v. injection of 50 µg of recom-binant human TNF in physiological saline was administered and splenocytes were harvested 3 days later. A cell fusion was then performed with mouse myeloma P3X63Ag8.653 cells using conventional methods. Hybridomas secreting fully human IgGs against human TNF were detected using an enzyme immunoassay and were subcloned twice by limiting dilution. The anti- bodies secreted into the cell supernatant were purified by protein A affinity chromatography. The mAbs were tested for human TNF-alpha binding. GenTNV 148.26.12 (golimumab), the most potent of these antibodies, was selected for further development. The closest matching human germline sequences to golimumab were IGHV3-30.3 (95% identical) and IGKV3-11 (99% identical), both of which were present in the transgenic mice.

Simponi is produced by a recombinant cell line cultured by continuous perfusion and is purified by a series of steps that includes measures to inactivate and remove viruses.

FDA class: Biologics BLA

Approvals: Date = 20090424; BLA

Indications: [Full text of the " "Indications and USAGE" section of the product insert/labeling]:

1.1 Rheumatoid Arthritis:

SIMPONI, in combination with methotrexate, is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis.

1.2 Psoriatic Arthritis:

SIMPONI, alone or in combination with methotrexate, is indicated for the treatment of adult patients with active psoriatic arthritis.

1.3 Ankylosing Spondylitis:

SIMPONI is indicated for the treatment of adult patients with active ankylosing spondylitis.

[Full text of the European Union indications:]:

In combination with methotrexate, for the treatment of moderate-to-severe, active RA in adult patients when the response to disease-modifying anti-rheumatic drug (DMARD) therapy, including methotrexate, has been inadequate. SIMPONI has also been shown to improve physical function in this patient population.

Alone or in combination with methotrexate, for the treatment of active and progressive PsA in adult patients when the response to previous DMARD therapy has been inadequate. SIMPONI has also been shown to improve physical function in this patient population.

For the treatment of severe, active AS in adult patients who have responded inadequately to conventional therapy.

Status: On June 27, 2008, Centocor filed a BLA with FDA seeking approval of Simponi for monthly subcutaneous treatment for adults with active forms of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

On March 18, 2008, Centocor filed an MAA with the European Union seeking approval for the same indications:.

On April 13, 2009, Simponi received approval in Canada for once-monthly, subcutaneous therapy for the treatment of moderately to severely active rheumatoid arthritis (RA), active psoriatic arthritis (PsA) and active ankylosing spondylitis (AS).

On April 22, 2009, FDA approved the BLA. This included an “exclusively designed prefilled syringe” to deliver Cimzia, developed with the direct input of RA patients. Simponi is the first monthly, self-injectable anti–TNF-alpha therapy approved to treat adults with: moderately to severely active rheumatoid arthritis (RA) with the medicine methotrexate; active psoriatic arthritis (PsA) alone or with the medicine methotrexate; and active ankylosing spondylitis (AS).

Simponi's U.S. product insert includes a "black box" warning concerning risk of serious infections (much as other TNF antibodies do).

On June 26, 2009 Simponi received EMA recommendation for approval and Oct. 6, 2009, Simponi received European Union (EU) approval as a once-monthly, subcutaneous therapy for the treatment of moderate-to-severe, active rheumatoid arthritis (RA), active and progressive psoriatic arthritis (PsA) and severe, active ankylosing spondylitis (AS).

In Oct. 2010, Centocor Ortho Biotech Inc., Johnson & Johnson, filed a sBLA to expand the use of Simponi to treat joint damage associated with RA. In Jan. 2011, the European Union approved Simponi in combination with methotrexate for the treatment of adults with severe, active and progressive RA not previously treated with methotrexate, and for the reduction in the rate of progression of joint damage as measured by X-ray in patients with RA.

In July 2011, FDA issued J&J a Complete Response letter (CRL) for its sBLA to expand approval to include inhibiting the progression of structural damage, inducing major clinical response (MCR) and maintenance of reduction of signs and symptoms and maintenance of improved physical function in the treatment of moderately to severely active rheumatoid arthritis (RA).

Tech. transfer: Regarding its UltiMAb Human Antibody Development System and related Mab technologies, Medarex asserts, "Our unique technology platform constitutes what we believe to be the most complete technology solution available in the marketplace for generating fully human antibodies and enables us to produce antibodies that we believe set the industry standard in that they (i) are fully human, (ii) are of a very high affinity, and (iii) can be produced and manufactured relatively quickly and efficiently. We are not aware of any licenses required to create fully human antibodies using our UltiMAb technology platform to a target owned by the user except under patents currently owned or licensed by us." This indicates that Medarex believes that its Mabs are not covered by the broad Cabilly-Boss antibody expression patent held by Genentech (see the Monoclonal Antibodies main entry).

Although Medarex's earliest patents in its Mab portfolio will expire starting in 2008, the majority of the HuMAb-Mouse technology patents expire between 2011 and 2015.

UltiMAb-related U.S. patents include 7,135,287, "Human antibodies," Nov. 7, 1996, assigned to Medarex. Claim 1 states, " A method of producing a human antibody display library, comprising: introducing a nucleic acid encoding a protein immunogen into a transgenic mouse whose genome comprises a plurality of human immunoglobulin genes that can be expressed to produce a plurality of human antibodies, isolating a population of nucleic acids encoding human antibody chains from lymphatic cells of the transgenic mouse; forming a library of display packages displaying the antibody chains, wherein a library member comprises a nucleic acid encoding an antibody chain, and the antibody chain is displayed from the package."

In May 2009, shortly after Simponi U.S. approval, Abbott Labs. (source for competing Humira) filed a patent (counter)infringement suit against Centocor. Centocor/J&J and New York Univ. had previously filed an infringement suit against Abbott concerning Humira (see related entry).

Bayer had filed challenges against Centocor/J&J alleging infringement of U.S. 5,654,407, Human anti-TNF antibodies." However, Bayer ended the suit after Bayer the district court judge interpreted the claimed term “Human monoclonal antibodies” specifically as including “low affinity, referring to the strength of the antibody’s attachment to TNF, and that don’t neutralize the protein.”

Bayer's equivalent European patent (EP0614984) was involved in post grant opposition proceedings at EPO (opposed by J&J and Abbott). This patent was initially revoked by EPO but the Technical board of appeal reversed this decision, the patent was issued and Bayer launched its golimumab/Simponi product in Europe.

In Jan 2011, a federal judge entered a final judgment of no infringement for Centocor/J&J in the U.S. District Court for the District of Massachusetts on Friday. Centocor and Bayer had entered a stipulation for the final judgment, agreeing that patent 5,654,407 has not been infringed due to the Judge's (Saylor) claim construction ruling, which was handed down in Dec. 2010.

U.K. has granted an SPC for EP0614984, extending U.K. coverage to Feb. 20, 2019. Trials: Centocor claims to have conducted, "the most comprehensive Phase 3 development program to date for an anti-TNF-alpha biologic therapy." Golimumab is currently in Phase II trials for the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis and is being investigated for administration by either monthly subcutaneous injection and every 12-week intravenous (IV) infusion.

Five pivotal Phase III trials supported the BLA filing. These include the GOlimumab Before Employing methotrexate as the First-line Option in the treatment of Rheumatoid arthritis of Early onset (GO-BEFORE) study; the GOlimumab FOR subjects With Active RA Despite MTX (GO-FORWARD) study; and A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Human Anti-TNF-alpha Monoclonal Antibody, Administered Subcutaneously in Subjects with Active Rheumatoid Arthritis and Previously Treated with Biologic Anti-TNF-alpha Agent(s) (GO-AFTER)

In Nov. 2007, positive primary endpoint study findings from the Golimumab - A Randomized Evaluation of Safety and Efficacy in Subjects with Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody (GO-REVEAL) trial and the Golimumab - A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection (SC) Given Every Four Weeks (GO-RAISE) trial were reported.

In Oct. 2008, results were reported from the GOlimumab After Former anti-TNF Therapy Evaluated in RA (GO-AFTER) Phase III trial. Every four week subcutaneous injections of golimumab, 50 mg or 100 mg, were studied in 461 patients who had active RA and who were previously treated with anti-TNF treatments, but where anti-TNF treatment had been discontinued due to lack of efficacy (58%), intolerance (17%) or other reasons (40%). Patients continued to receive stable doses of methotrexate, sulfasalazine and/or hydroxychloroquine if they were receiving them at baseline. Golimumab-treated patients who had discontinued previous anti-TNF treatment for any reason experienced significant improvements in physical function, as measured by the Health Assessment Questionnaire (HAQ). HAQ assesses the degree of difficulty a person has in accomplishing tasks in eight functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and other activities of daily living). At week 24, the proportion of patients experiencing clinically relevant improvement (increase in HAQ score of at least 0.25 from baseline) was significantly greater for golimumab-treated patients compared with those receiving placebo. More than half of patients in the combined golimumab group (52%) achieved the measure, compared with 34% of placebo-treated patients (P < 0.001).

In Oct. 2008, results were also reported from the GOlimumab FOR subjects With Active RA Despite Methotrexate (GO-FORWARD) Phase III trial of 50 mg and 100 mg doses of golimumab in 444 RA patients who had active RA and were previously treated with methotrexate. At week 24, the mean improvement in FACIT-F was 7.2 +/- 8.6 in the combined golimumab group, compared with an improvement of 2.2 +/- 9.5 among patients receiving methotrexate alone (P < 0.001). At 24 weeks, 70 percent of those receiving golimumab plus methotrexate experienced a clinically relevant improvement in physical function, compared with 39 percent of patients receiving methotrexate alone (P < 0.0001). Also at week 24, the combined golimumab group achieved a mean improvement in HAQ of 0.46 +/- 0.53, compared with an improvement of 0.13 +/- 0.58 among patients receiving methotrexate alone (P < 0.001).

Medical: Simponi is administered by 50 mg subcutaneous injection once a month (patient self-administration) ; and is also being studied as an every 12-week intravenous (IV) infusion therapy. For comparison, Enbrel is given as a subcutaneous injection once a week; Humira is adminstered by subcutaneous injection every other week; and Remicade is given by infusion every eight weeks.

Market: Total worldwide sales were about $674 million in 2011 and $323 million in 2010. Merck's sales were $264 million in 2011, $97 million in 2010, and $4 million in 2009.

With its to its more convenient subcutaneous (and eventually likely intravenous) dosing, Golimumab was originaly expected to become a leader among TNF Mabs, indicating it will likely reach blockbuster (>$1 billion/year) sales. Remicade is dosed every eight weeks for maintenance therapy and is administered as an intravenous (IV) infusion. Enbrel and Humira are administered by subcutaneous (SC) injection weekly or every other week, respectively. In contrast, golimumab is administered by SC injection every four weeks and appears on track to also later be approved for IV infusion every 12 weeks. Ultimately, the costs and perceived cost-benefit ratios of competing products likely be the primary determinant of CNTO-148 pricing.

In Oct. 2010, the National Institute for Health and Clinical Excellence, U.K., issued a preliminary rejection of Simponi use on the NHS for the treatment of psoriatic arthritis, after ruling that it is not as effective as the current standard therapy, Amgen/Pfizer's Enbrel (etancercept); and subsequently issued preliminary recommendations rejecting the use of Simponi to treat rheumatoid arthritis patients who have already tried conventional disease-modifying anti-rheumatic drugs (DMARDs) and TNF inhibitors but for whom Roche’s MabThera (rituximab) is still an appropriate option, because it is “associated with greater costs and fewer QALYs” than Simponi. Annual therapy with Simponi for RA was estimated to cost around £9,294, NICE was then recommending Abbott Laboratories Humira (adalimumab) and J&J/Merck's Remicade (infliximab) as well as Enbrel for the treatment of psoriatic arthritis in people who have peripheral arthritis.

In June 2011, the National Institute for Health and Clinical Excellence, U.K., published final guidance recommending the use of Simponi for ankylosing spondylitis by the NHS in England and Wales, but only when other treatments have failed. Guidance stipulates that Simponi, in combination with methotrexate, should be considered for adults whose disease has not responded to both conventional and other disease-modifying antirheumatic drugs (DMARDs), when used as per the other tumor necrosis factor inhibitor treatments already available on the NHS – Amgen/Pfizer's Enbrel (etanercept), Johnson & Johnson/Merck's Remicade (infliximab) and Abbott Laboratories Humira (adalimumab). In all circumstances, NICE stated that Simponi is only being backed for funding on the proviso that MSD provides the 100 mg dose of Simponi at the same price as the 50mg version, to ensure it remains cost-effective. Annual cost for treatment was calculated to be £9,155 per patient per year. Merck's submission set the cost of golimumab at £775 ($1,242) for a 50 mg pre-filled injection pen, with an estimated annual cost of £9,295. With the agreed patient-access scheme, the cost of the 100 mg dose is the same as the 50 mg dose.

Competition: Golimumab will have to compete against other established and new TNF antagonist biologics.

a) Remicade from the same marketing companies (discussed above);

b) Humira, containing a fully human monoclonal antibody (like CNTO-148), marketed by Abbott Labs. in the U.S, Europe and nearly all countries worldwide;

b) Enbrel, containing a fully human recombinant antibody-like construct marketed by Amgen in the U.S. and by Wyeth internationally;

c) Cimzia, containing a pegylated recombinant humanized (5% murine) TNF antibody (two polyethylene glycol polymer strands attached), recently approved in the U.S., marketed worldwide by the UCB Group. With its PEG modification and humanization, like CNTO-148, Cimzia will be administered once monthly subcutaneously, like CNTO-148, allowing self-admininstration by patients much less frequently than the other products.

Other recombinant therapeutics expected to compete somewhat with CNTO-148 and other TNF antagonists for RA indications: include Orencia from Bristol-Myers Squibb Co. (BMS), Rituxan from Genentech, and Rilonacept (IL-1 Trap) from Regeneron Pharmaceuticals, Inc. Orencia was approved in the U.S. for RA in 2005, and Rituxan was approved for RA in 2006, but only for use after treatment with a TNF antagonist (third-line treatment). Rilonacept was approved in 2008. Between approvals only for third-line use and these having differeent mechanisms of action, these do not pose serious direct competiton for CNTO-148.

J&J expects (hopes) that the “exclusively designed prefilled syringe” used to deliver Simponi will provide a competitive advantage. This was designed in collaboration with OXO International, Ltd., a noted consumer products, such as kitchen tools, manufacturer. The syringe was designed for use by patients with different grip styles and strengths. Patients worked with the design and engineering teams.

In many respects, as the biopharmaceutical industry matures, CNTO-148 has followed a developing pattern of innovator companies bringing out improved, second-generation products that compete with their own first-generation products and the first-generation or new(er) products from other competitors (i.e., a new, improved product will compete against a first-generation product from the same company). The situation may be compared to that with first- and second-generation erythropoietins (e.g., Epogen and Aranesp from Amgen) and alpha interferon products (e.g., Intron-A and PEG-Intron from Schering-Plough, and Roferon A and Pegasys from Roche), with the later-generation products offering improvements, at least in terms of potency, less frequent dosing/administration and often efficacy, with improved cost-benefit ratios. This allows their marketers to capture significant market share, particularly from first-generation products, while retaining or expanding the market share for their portfolio of related products.

CNTO-148 and all of the other TNF antagonist biologics are used mostly (or upon initial approval) for second-line treatment for pateints not responding or having excessive adverse effects from first-line treatment with methotrexate, an inexpensive drug long on the market, with many generic versions available, but with adverse effects and limited efficacy in some or many patients for rheumatoid arthritis and other anti-inflammtory indications:.