Ustekinumab (CNTO 1275)
2007
Findings in the treatment of moderate to severe plaque psoriasis
These are the archived findings from an international, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial evaluating ustekinumab (CNTO 1275) in the treatment of moderate to severe plaque psoriasis conducted in 2007. Thanks to Jim Webert for all his effort in gathering the info below and posting to the archive. Jim took time away from his experimental project, testing the effectiveness of household products on the environment to protect this information for use in his graduate level program at the University of North Carolina. He is the man responsible for the discovery of weed agent and insect repellent properties of enzymes found in the digestive tract of certain amphibians. Each of the below reports was produced by a different reporting agent & all are identified for accountability.
Ustekinumab, is a human immunosuppressive drug developed by the biotechnology company Centocor. It is a laboratory-manufactured, monoclonal antibody directed against interleukins IL-12 and IL-23. Since 2009, ustekinumab has been approved in US, Canada, and Europe for the treatment of plaque psoriasis and psoriatic arthritis. In September 2016, Janssen announced that the FDA approved the medication for the treatment of moderate-severe Crohn's disease.
The new owner of this site's domain decided to retain an edited version of the information that was once available in 2007 on this site. He felt this information is important and should remain accessible online. Most of the content is from other outside sources.
The new owner's post doctorate thesis involved human immunosuppressive drugs such as ustekinumab, which may explain, in part, his interest in buying this expired domain after I discovered it was available. His father had suffered from psoriatic arthritis for years. Psoriatic arthritis can cause swelling, stiffness and pain in and around the joints, cause nail changes and overall fatigue. I remember our decision to move his father to an assisted living facility was due to a large degree to the debilitating effects of Psoriatic arthritis. His father explained that one way he's found to mitigate the discomfort is reading - specifically philosophical topics. Reading is a therapeutic intervention that has taken him from Aristotle, Newton, Descartes. He is especially interested in existentialism - and the arguments for the nature of existence. I learned that starting with the concept of nothing, philosophers have derived both the existence and the absence of God. He took me to this brilliant article that has a very interesting and detailed post on many of the aspects of "nothing" and how the idea is handled by the scholars, the media, Google, and the vernacular. Meanwhile the advances in the treatment of Psoriatic arthritis with ustekinumab seems promising.
This site's information shows what was happening in 2007 regarding the tests and trials that were being performed. At the time Ustekinumab was a novel biologic therapy.
Sep 25, 2007
Pivotal Ustekinumab (CNTO 1275) Phase 3 Data to Debut at World Congress of Dermatology Meeting
HORSHAM, Pa., Sept. 25 2007 /PRNewswire/ -- Findings from an international, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial evaluating ustekinumab (CNTO 1275) in the treatment of moderate to severe plaque psoriasis will be presented for the first time at the 21st meeting of the World Congress of Dermatology, which takes place from Sept. 30 to Oct. 5, 2007 in Buenos Aires, Argentina.
The presentation, entitled CNTO 1275 (anti-IL-12/23p40) Treatment of Psoriasis: Phase 3 Trial Results will take place on Wednesday, Oct. 3, 2007 from 11 a.m. to 1 p.m. local time (GMT +3:00; 10:00 a.m. to 12:00 p.m. EDT), Room A, La Rural Convention Center, Buenos Aires, Argentina.
These first reported findings will be the subject of a live press briefing and webcast, which will be broadcast from the World Congress of Dermatology on Wednesday, Oct. 3 at 2 p.m. EDT. Media and analysts are invited to register at http://www.CNTO1275WCD.com and listen live on Oct. 3 as investigators from the trial will review and discuss the data.
About Ustekinumab
Ustekinumab is a new, fully-human monoclonal antibody in Phase 3 development by Centocor, Inc. for the treatment of moderate to severe plaque psoriasis and is being investigated as an infrequently-administered subcutaneous injection. Ustekinumab is a novel biologic therapy that targets interleukin 12 (IL-12) and interleukin 23 (IL-23), naturally occurring proteins that are important in normalizing the immune system and that are also believed to play a role in immune-mediated inflammatory diseases.
Centocor discovered ustekinumab and has exclusive marketing rights to the product in the United States. Janssen-Cilag companies will market ustekinumab in all countries outside of the United States.
About Psoriasis
Psoriasis is a chronic, immune-mediated disease that results from inflammation in the skin and overproduction of skin cells that accumulate on the surface causing red, scaly plaques that may itch and bleed. This chronic inflammation is driven in part by IL-12 and IL-23, cytokines involved in the regulation of the body's immune response. It is estimated that 125 million people worldwide have psoriasis, including two percent of both the U.S. and European populations, or some 7.5 million Americans and 10 million Europeans. Nearly one-quarter of people with psoriasis have cases that are considered moderate to severe.
About Centocor, Inc.
Centocor is harnessing the power of world-leading research and biomanufacturing to deliver innovative biomedicines that transform patients' lives. Centocor has already brought innovation to the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, pediatric Crohn's disease and psoriasis.
The world leader in monoclonal antibody production and technology, Centocor has brought critical biologic therapies to patients suffering from debilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary of Johnson & Johnson.
About Janssen-Cilag
The Janssen-Cilag companies are members of the Johnson & Johnson Family of Companies, the world's most comprehensive and broadly based manufacturer of health care products, as well as a provider of related services, for the consumer, pharmaceutical, and medical devices and diagnostics markets. Janssen-Cilag companies have a long track record in developing and marketing treatments for central nervous system disorders, pain management, infectious diseases, gastrointestinal disorders and oncology.
SOURCE Centocor, Inc.
Centocor, Inc. (JNJ) Announces Promising Phase 3 Trial Results
BUENOS AIRES, Argentina, Oct. 3 2007/PRNewswire/ -- The first reported findings from an international, Phase 3 study showed that more than two-thirds of patients with moderate to severe plaque psoriasis receiving two doses of ustekinumab (CNTO 1275) achieved at least a 75 percent reduction in psoriasis at week 12, the primary endpoint of the study, as measured by the Psoriasis Area and Severity Index (PASI 75). Importantly, findings also showed that following one additional dose at week 16, a substantial proportion of patients receiving ustekinumab maintained a PASI 75 response through week 28. Data from the study, presented at the World Congress of Dermatology, involved more than 1,200 subjects and showed that within four weeks of initiating treatment with ustekinumab, patients experienced significant and clinically meaningful improvements in quality of life measures compared with patients receiving placebo. Ustekinumab is a new, fully-human monoclonal antibody with a novel mechanism of action that targets the cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23), and is currently in Phase 3 development by Centocor, Inc. for the treatment of moderate to severe plaque psoriasis.
These data, presented at the 21st meeting of the World Congress of Dermatology, will be the subject of a live press briefing and webcast (www.cnto1275wcd.com) today at 2 p.m. EDT featuring Craig Leonardi, MD, St. Louis University Medical School, St. Louis, MO, Kristian Reich, MD, Georg- August-University, Gottingen, Germany, Silvia Fernandez Barrio, executive director, Civil Association of Psoriasis Patients of Argentina, Buenos Aires, Argentina, and Tom Schaible, PhD, vice president, Medical Affairs, Centocor, Inc.
"These findings provide further evidence of the role of IL-12/23 in the pathogenesis of psoriasis and the promise that a new therapeutic approach like ustekinumab may hold for dermatologists and their patients living with this chronic, immune-related disease," said Craig Leonardi, MD, St. Louis University Medical School and lead investigator of the study. "The efficacy and safety data for ustekinumab in the treatment of psoriasis are exciting for the dermatology community."
At week 12 of this Phase 3, multicenter, randomized, double-blind, placebo-controlled trial, 67 percent of patients treated with 45 mg ustekinumab (two 45 mg doses four weeks apart) and 76 percent of patients treated with 90 mg ustekinumab (two 90 mg doses four weeks apart), achieved PASI 75 compared with four percent of patients receiving placebo (P < 0.001 for each comparison versus placebo). Also at week 12, 42 percent of patients in the 45 mg ustekinumab dosing group and 51 percent of patients in the 90 mg ustekinumab dosing group achieved PASI 90, or nearly complete clearance of psoriasis, compared with one percent of patients receiving placebo (P < 0.001 for each comparison versus placebo). Similar response rates were observed in the placebo group 12 weeks after crossover to treatment with ustekinumab. After one additional dose at week 16, responses were maintained through week 28, which is consistent with the maintenance regimen of every 12-week dosing currently being evaluated in the Phase 3 program. Improvements in clinical measures were paralleled with improvements in quality of life measures.
"These findings show that by targeting IL-12/23 with ustekinumab, we may be able to offer dermatologists and patients a new, promising biologic therapy with an infrequent dosing regimen for the treatment of psoriasis," said Jerome A. Boscia, MD, senior vice president, Clinical Research and Development, Centocor, Inc. "We are encouraged by the results from the Phase 3 program and look forward to collaborating with regulatory authorities around the world in an effort to bring ustekinumab to physicians and patients in need of new therapeutic options."
Additionally, data will be presented at the World Congress of Dermatology that show that as early as week four patients treated with either 45 mg or 90 mg ustekinumab experienced significant improvements in quality of life measures compared with patients receiving placebo. At week four, according to the Dermatology Life Quality Index (DLQI), a 10-item questionnaire that measures the impact of psoriasis on quality of life and patient burden of disease, median DLQI improvement was 6.0 for 45 mg and 6.0 for 90 mg versus 1.0 for placebo (each P < 0.001 versus placebo). An improvement of five or more from baseline is considered to be clinically meaningful. At week 12, 72 percent of patients receiving 45 mg ustekinumab and 77 percent of patients receiving 90 mg ustekinumab achieved a reduction of at least five points in DLQI score compared with 21 percent of patients in the placebo group (P < 0.001 for each comparison versus placebo). Also at week 12, a total of 37 percent of patients receiving the 45 mg ustekinumab and 39 percent of patients receiving the 90 mg ustekinumab achieved a DLQI score of zero, indicating no impact of psoriasis or the treatment on quality of life, compared with one percent of those receiving placebo (P < 0.001 for each comparison versus placebo). Upon crossing over to treatment with ustekinumab, patients initially randomized to placebo experienced similar improvements in DLQI after 12 weeks.
"Psoriasis is an inflammatory disease that can cause severe emotional, physical and social burdens for patients," said Richard Langley, MD, Dalhousie University, Halifax, Nova Scotia, Canada, and trial investigator. "While more therapies have become available for the treatment of psoriasis over the years, dermatologists need additional options to manage this chronic disease, and ustekinumab would represent a much needed addition in the treatment armamentarium."
About the PHOENIX 2 Trial
The Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Efficacy and Safety of CNTO 1275 in the Treatment of Subjects with Moderate to Severe Plaque-type Psoriasis Followed by Long-term Extension 2 (PHOENIX 2) trial involved 1,230 patients with chronic plaque psoriasis. Patients were randomized to receive subcutaneously administered ustekinumab or placebo. Patients randomized to receive ustekinumab received 45 mg or 90 mg doses at weeks 0 and 4 followed by the same dose every 12 weeks. Patients in the placebo group crossed over to receive either 45 mg or 90 mg doses of ustekinumab at weeks 12 and 16 and every subsequent 12 weeks. The primary end point of the study was the proportion of patients who achieved PASI 75 at week 12.
Through week 12, the placebo-controlled portion of the study, the percentages of study participants who experienced at least one adverse event (AE) were comparable between the placebo group (49 percent) and the ustekinumab 45 mg group (53 percent) and 90 mg group (48 percent). Discontinuation due to an AE occurred in 0.2 percent and one percent of patients in the respective ustekinumab groups, compared with two percent of patients in the placebo group. Two percent and one percent of patients receiving 45 mg or 90 mg ustekinumab, respectively, experienced at least one serious AE compared with two percent of patients receiving placebo.
About Psoriasis
Psoriasis is a chronic, immune-mediated disease that results from inflammation in the skin and overproduction of skin cells that accumulate on the surface causing red, scaly plaques that may itch and bleed. This chronic inflammation is driven in part by IL-12 and IL-23, cytokines involved in the regulation of the body's immune response. It is estimated that 125 million people worldwide have psoriasis, including two percent of both the U.S. and European populations, or some 7.5 million Americans and 10 million Europeans. Nearly one-quarter of people with psoriasis have cases that are considered moderate to severe.
About Ustekinumab
Ustekinumab is a new, fully-human monoclonal antibody in Phase 3 development by Centocor, Inc. for the treatment of moderate to severe plaque psoriasis, and is being investigated as an infrequently-administered subcutaneous injection. Ustekinumab is a novel biologic therapy that targets interleukin 12 (IL-12) and interleukin 23 (IL-23), naturally occurring proteins that are important in normalizing the immune system and that are also believed to play a role in immune-mediated inflammatory diseases.
Centocor discovered ustekinumab and has exclusive marketing rights to the product in the United States. Janssen-Cilag companies will market ustekinumab in all countries outside of the United States.
About Centocor, Inc.
Centocor is harnessing the power of world-leading research and biomanufacturing to deliver innovative biomedicines that transform patients' lives. Centocor has already brought innovation to the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, pediatric Crohn's disease and psoriasis.
The world leader in monoclonal antibody production and technology, Centocor has brought critical biologic therapies to patients suffering from debilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary of Johnson & Johnson.
About Janssen-Cilag
The Janssen-Cilag companies are members of the Johnson & Johnson Family of Companies, the world's most comprehensive and broadly based manufacturer of health care products, as well as a provider of related services, for the consumer, pharmaceutical, and medical devices and diagnostics markets. Janssen-Cilag companies have a long track record in developing and marketing treatments for central nervous system disorders, pain management, infectious diseases, gastrointestinal disorders and oncology.
(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the Centocor's and Janssen-Cilag's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2006. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov or on request from Johnson & Johnson. Neither Centocor nor Janssen-Cilag undertakes to update any forward- looking statements as a result of new information or future events or developments.)
CONTACT: Media, Michael Parks of Centocor, Inc., +1-215-325-4010, Mobile,
+1-215-983-8000; or Investors, Louise Mehrotra, +1-732-524-6491, Stan
Panasewicz, +1-732-524-2524, or Lesley Fishman, +1-732-524-3922, all of
Johnson & Johnson
Web site: http://www.cnto1275wcd.com/
Pivotal Ustekinumab (CNTO 1275) Phase 3 Data to Debut at World Congress of Dermatology Meeting
Sep 25, 2007, 01:00 ET from Centocor, Inc.
HORSHAM, Pa., Sept. 25 /PRNewswire/ -- Findings from an international, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial evaluating ustekinumab (CNTO 1275) in the treatment of moderate to severe plaque psoriasis will be presented for the first time at the 21st meeting of the World Congress of Dermatology, which takes place from Sept. 30 to Oct. 5, 2007 in Buenos Aires, Argentina.
The presentation, entitled CNTO 1275 (anti-IL-12/23p40) Treatment of Psoriasis: Phase 3 Trial Results will take place on Wednesday, Oct. 3, 2007 from 11 a.m. to 1 p.m. local time (GMT +3:00; 10:00 a.m. to 12:00 p.m. EDT), Room A, La Rural Convention Center, Buenos Aires, Argentina.
These first reported findings will be the subject of a live press briefing and webcast, which will be broadcast from the World Congress of Dermatology on Wednesday, Oct. 3 at 2 p.m. EDT. Media and analysts are invited to register at http://www.CNTO1275WCD.com and listen live on Oct. 3 as investigators from the trial will review and discuss the data.
About Ustekinumab
Ustekinumab is a new, fully-human monoclonal antibody in Phase 3 development by Centocor, Inc. for the treatment of moderate to severe plaque psoriasis and is being investigated as an infrequently-administered subcutaneous injection. Ustekinumab is a novel biologic therapy that targets interleukin 12 (IL-12) and interleukin 23 (IL-23), naturally occurring proteins that are important in normalizing the immune system and that are also believed to play a role in immune-mediated inflammatory diseases.
Centocor discovered ustekinumab and has exclusive marketing rights to the product in the United States. Janssen-Cilag companies will market ustekinumab in all countries outside of the United States.
About Psoriasis
Psoriasis is a chronic, immune-mediated disease that results from inflammation in the skin and overproduction of skin cells that accumulate on the surface causing red, scaly plaques that may itch and bleed. This chronic inflammation is driven in part by IL-12 and IL-23, cytokines involved in the regulation of the body's immune response. It is estimated that 125 million people worldwide have psoriasis, including two percent of both the U.S. and European populations, or some 7.5 million Americans and 10 million Europeans. Nearly one-quarter of people with psoriasis have cases that are considered moderate to severe.
About Centocor, Inc.
Centocor is harnessing the power of world-leading research and biomanufacturing to deliver innovative biomedicines that transform patients' lives. Centocor has already brought innovation to the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, pediatric Crohn's disease and psoriasis. The world leader in monoclonal antibody production and technology, Centocor has brought critical biologic therapies to patients suffering from debilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary of Johnson & Johnson.
About Janssen-Cilag
The Janssen-Cilag companies are members of the Johnson & Johnson Family of Companies, the world's most comprehensive and broadly based manufacturer of health care products, as well as a provider of related services, for the consumer, pharmaceutical, and medical devices and diagnostics markets. Janssen-Cilag companies have a long track record in developing and marketing treatments for central nervous system disorders, pain management, infectious diseases, gastrointestinal disorders and oncology.
SOURCE Centocor, Inc.
There was a JPM report JNJ's CNTO-1275 as potential best in class for psoriasis today (biologic delivered via subcutaneous injection, not oral)
US Biotech: Psoriasis Market
JNJ's CNTO-1275: Best-in-Class Profile?
Phase III PHOENIX-2 results for JNJ’s CNTO-1275 in psoriasis were better than expectations and indicate potentially a best-in-class profile. In the study, 76% of patients receiving 90mg CNTO-1275 achieved a PASI- 75 (versus 4% of placebo pts). On the safety side, the profile was impressive, which could be a driver of adoption. Specifically, the data did not show a cardiovascular signal as feared and in our view could position anti-IL-12/23 agents (incl ABT-874) as a more significant long-term threat to Enbrel share compared to other anti-TNFs. Net-Net, Enbrel is likely to lose share in psoriasis, but that could be partially offset by market growth, spurred by promotion by Abbott (Humira) and JNJ (CNTO-1275). Hence, we see a modest negative impact to our Enbrel ests, where a worst case scenario could lead to $150M revs and $0.05 EPS (-1%) at risk in 2010.
• Efficacy data impressive. PHOENIX-2 data at the World Conference on Dermatology showed that CNTO 1275 met the primary endpoint of improvement in PASI-75 score, where two injections of 90mg 4 wks apart resulted in 76% achieving a 75% reduction in psoriasis (PASI-75). In the lower dose group (45mg x2), the PASI-75 was 67%, while the placebo patients showed a PASI-75 of 4%. Recall that ph III 16-wk PASI-75 scores of Humira were 71% (n=1,212) and 80% (n=271), and 12-wk Enbrel PASI-75 scores were 32-47% depending on dose regimen.
• Safety the driver of uptake. Physician comfort with Enbrel has been due to its ~10 year experience on the market with more than 450,000 pts treated. Dermatologists favor safety and the black box warnings for anti- TNF antibodies for serious infections have underscored Enbrel's market dominance. However, we view the favorable safety profile for 1275 (see page 2) as likely to drive strong uptake in the market.
• Market growth to offset Enbrel share declines. Although we expect Enbrel share to decrease over time from current levels (~80%) due to the market entry of Humira (mid-08e) and ’1275 (YE08e), we expect multiple promotional voices to drive increased biologics adoption among dermatologists (currently <20%). Net-net, we estimate that a higher than modeled 2010 penetration of ’1275 (to the tune of 35% of all biologics) could lead to $150M revenue downside to Amgen in 2010.
• Remaining Neutral on AMGN; Overweight on MEDX. Slowing Enbrel growth is not likely to offset Amgen losses in its core anemia market, thus we remain Neutral. OW-rated Medarex has rights to a single-digit royalty on ’1275 sales free of any associated costs, where upside to our ’1275 ests could be significant (every $100M in '1275 sales is worth $0.03 to our 2010 Medarex EPS est of $0.60).
CNTO 1275 Efficacy Similar to TNFs, But Impressive on Safety
Efficacy data for CNTO 1275 appears to be in line with that of anti-TNF antibodies Humira and Remicade, and compares favorably to Enbrel (see Table 1 for details). However, the safety profile of CNTO 1275 appears to be no different than that of placebo, which we view as very encouraging for its commercial prospects. PHOENIX-2 data revealed no cardiovascular adverse events (AEs), feared based on the phase II dataset (Krueger et al, NEJM (2007) 356: 580-592) where 2 patients had myocardial infarctions compared to none in the placebo arm. No serious infections were observed in patients receiving CNTO 1275, and the most common AE (nasopharyngitis) only occurred with only 7% frequency in each arm.
CNTO 1275 Safety Data Comparable to Enbrel?
We believe the PHOENIX-2 safety data is competitive with Enbrel’s, which is viewed by dermatologists as a relatively safe and well-known drug. We note that the CNTO 1275 safety data compares rather favorably to Humira, which is associated with increased risk of infections. We also note Remicade’s well-characterized association with reactivation of tuberculosis and serious infections, as well as its hypersensitivity reactions and weaker positioning due to IV administration.
Table 1: Comparative Profiles of Phase III Results of Biologics in Psoriasis Agent Dose (duration) PASI 75 Safety
CNTO 1275 90mg at 0, 4 wks, then Q12wk 76% AE rates similar: 48%(90mg dose); 53% (45mg dose) and 49% (pbo)
(PHOENIX 2) 45mg at 0, 4 wks, then Q12wk 67% Similar rates of infection (22% combined dose vs. 20% pbo)
(12 weeks) 4% (placebo) No cardiovascular-related AEs n = 1,200 No cases of tuberculosis or opportunistic infections Humira 80 mg x 1 followed by 40 mg EOW 71% Higher overall AE rate (62% vs. 56% pbo)
(REVEAL) (16 weeks) 6.5% (placebo) Higher rates of infections in Humira arm (29% vs. 22% pbo) n=1,212 Similar rates of AEs Humira 80 mg x 1 followed by 40 mg EOW 80% (CHAMPION) (16 weeks) 36% (MTX) n = 271 19% (placebo) Enbrel At 12 weeks Same rate of AEs (Enbrel vs. pbo)
(Etanercept Psoriasis 25 mg 1x/wk 14% (25mg QW) Injection site reactions most frequent Study Group) 25 mg 2x/wk 32% (25mg BIW) (13% in 50mg BIW arm vs. 7% pbo) 50 mg 2x/wk 47% (50mg BIW) No cases of tuberculosis or opportunistic infections n = 673 (24 weeks) 4% (placebo) Remicade At 10 weeks Heightened risk of serious infections due to B cell depletion (EXPRESS II) 3 and 5 mg/kg (0,2,6 wk, then every 8 wks) 70% (3 mg/kg) Injection site reactions common(20% of pts) 75% (5 mg/kg) Hypersensitivity reactions common (chimeric antibody) n = 835 (46 weeks) 2% (placebo) 10% generate anti-Remicade antibodies Remicade At 10 weeks (SPIRIT) 3 and 5 mg/kg (0,2,6 wk, followed 88% (3 mg/kg) by add'l dose based on sPGA score) 72% (5 mg/kg) n = 249 (26 weeks) 6% (placebo) Source: Company data, Leonardi et al, WCD 2007 (www.cnto1275wcd.com); Menter et al, AAD 2007; Leonardi et al, NEJM 349:2014-2022 (2003); product labels.
Dosing Convenience Also Favors CNTO 1275
The dosing regimen for CNTO 1275 is two at-home subcutaneous (s.c.) injections four weeks apart, followed by one injection once per 12 weeks. This long interval of dosing will enhance its competitive positioning given Remicade usage by IV only, Enbrel dosed s.c. twice weekly (transitioning to once weekly), and Humira given s.c. every other week.
More Background On CNTO1275WCD.com
CNTO1275WCD.com is a particularly interesting surviving piece of pharmaceutical and medical-internet history. Rather than being a conventional corporate website, patient portal, medical practice site, or publication, the domain was created around a specific moment in the development of ustekinumab, the biologic drug then known by its experimental designation CNTO 1275.
In the fall of 2007, CNTO 1275 was still an investigational treatment being developed by Centocor, Inc., a Johnson & Johnson company, for moderate-to-severe plaque psoriasis. The 21st World Congress of Dermatology in Buenos Aires, Argentina, provided the setting for the first presentation of pivotal Phase 3 findings from a major clinical trial of the drug. CNTO1275WCD.com served as the online destination promoted to journalists, analysts, medical professionals and others who wanted to register for and listen to a live webcast discussing those findings.
Seen from today's perspective, the domain captures an unusually specific point in a drug's development: CNTO 1275 was promising enough to command international attention but had not yet become the approved prescription medicine Stelara. The website therefore documents the period when researchers were establishing the clinical case for a therapy that would subsequently become an important treatment for immune-mediated inflammatory diseases.
What CNTO1275WCD.com Was Created For
Contemporary announcements from Centocor make the original function of CNTO1275WCD.com unusually clear. On September 25, 2007, Centocor announced that pivotal Phase 3 data for ustekinumab would be presented at the 21st World Congress of Dermatology. The congress was being held in Buenos Aires from September 30 through October 5.
The scientific presentation was titled “CNTO 1275 (anti-IL-12/23p40) Treatment of Psoriasis: Phase 3 Trial Results.” It was scheduled for October 3 at the La Rural Convention Center in Buenos Aires.
Centocor simultaneously announced a live press briefing and webcast for October 3. Media representatives and analysts were specifically directed to CNTO1275WCD.com to register and listen as investigators reviewed and discussed the findings.
That establishes the domain's original role more precisely than simply describing it as a website about psoriasis. It was essentially a pharmaceutical communications microsite associated with a major scientific conference and an important clinical-trial announcement.
The domain name itself reflects this specialized purpose. “CNTO 1275” was Centocor's development designation for ustekinumab, while “WCD” referred to the World Congress of Dermatology.
Centocor, Johnson & Johnson and the Website's Ownership Context
The organization most directly associated with the original CNTO1275WCD.com campaign was Centocor, Inc. Contemporary announcements explicitly identified Centocor as the source and listed CNTO1275WCD.com as the website connected with the webcast.
Centocor was already a significant biotechnology company specializing in monoclonal-antibody therapies and was a wholly owned subsidiary of Johnson & Johnson. Its work included treatments for inflammatory diseases such as Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis and psoriasis.
Centocor had discovered ustekinumab and at the time held the U.S. marketing rights. Janssen-Cilag companies, also members of the Johnson & Johnson family, were responsible for marketing outside the United States.
The corporate names surrounding the drug subsequently changed. FDA records today identify Janssen Biotech, Inc. as the applicant associated with Stelara's biologics license. That later corporate identity should not obscure the historical context of CNTO1275WCD.com: in 2007, the company publicly promoting the experimental treatment and the webcast website was Centocor.
The domain has subsequently passed out of its original campaign role. Its historical value today lies primarily in preserving or recalling information associated with that 2007 event rather than functioning as the current official product website for Stelara.
The World Congress of Dermatology Connection
The location and timing of the website were central to its identity.
The 21st World Congress of Dermatology brought dermatologists and researchers from around the world to Buenos Aires in 2007. The congress represented an important venue for presenting new research, discussing treatment advances and exposing specialists to emerging therapies.
The CNTO 1275 presentation took place at La Rural, the large exhibition and convention complex in Buenos Aires. The meeting therefore gave Centocor an international scientific stage for revealing the Phase 3 results.
CNTO1275WCD.com extended that event beyond the physical convention center. Someone did not necessarily have to be sitting in the Buenos Aires presentation room to hear investigators discuss the results. Journalists and analysts could register online and listen to the subsequent press briefing by webcast.
That may seem routine today, when medical conferences commonly provide extensive digital access. In 2007, however, using a dedicated drug-and-conference domain to distribute a live scientific briefing represented the increasingly sophisticated way pharmaceutical companies were combining traditional medical meetings with online communications.
The Drug Behind the Domain
Ustekinumab is a fully human monoclonal antibody. Its mechanism distinguished it from several established biologic psoriasis treatments of the period.
The drug targets the p40 protein subunit shared by interleukin-12 and interleukin-23, cytokines involved in immune signaling and inflammatory processes. By binding to this shared component, ustekinumab interferes with IL-12- and IL-23-mediated pathways involved in psoriasis.
This mechanism was an important part of the scientific story surrounding CNTO 1275. Existing biologics had already demonstrated that targeted immune therapies could dramatically improve severe psoriasis, but investigators and pharmaceutical developers continued looking for treatments with strong efficacy, acceptable safety and more convenient dosing.
Ustekinumab's potential dosing schedule was therefore notable as well as its mechanism. The Phase 3 program evaluated injections at weeks 0 and 4 followed by considerably more widely spaced maintenance dosing.
Why Psoriasis Was Such an Important Target
Plaque psoriasis is much more than a cosmetic skin condition. It is a chronic immune-mediated inflammatory disease in which accelerated skin-cell production contributes to raised, scaly and inflamed plaques. Moderate-to-severe disease can cover substantial areas of the body and can affect physical comfort, daily activity, self-image, social relationships and emotional well-being.
That broader burden helps explain why the 2007 trial measured not only visible improvement in psoriasis but also quality of life.
One of the standard clinical measurements used in psoriasis trials is the Psoriasis Area and Severity Index, or PASI. A “PASI 75” response means that a patient's PASI score has improved by at least 75 percent from baseline. PASI 90 represents an even greater degree of improvement and approaches clearance of the disease.
These measurements became central to the CNTO 1275 story presented in Buenos Aires.
The PHOENIX 2 Trial
The results highlighted through the 2007 World Congress presentation came from PHOENIX 2, a large international Phase 3 study.
PHOENIX 2 enrolled 1,230 patients with moderate-to-severe chronic plaque psoriasis. It was multicenter, randomized, double-blind and placebo-controlled, providing a strong clinical design for comparing ustekinumab with placebo.
Participants were assigned to receive 45 mg of ustekinumab, 90 mg of ustekinumab or placebo. Patients receiving active treatment were given doses at weeks 0 and 4, with continued treatment subsequently evaluated at longer intervals.
The primary endpoint was the proportion of patients achieving PASI 75 at week 12.
The initial results were striking. At week 12, approximately 67 percent of patients in the 45 mg group and 76 percent in the 90 mg group achieved PASI 75. Only about 4 percent of placebo patients reached that endpoint.
Results at the higher PASI 90 threshold were also important. Approximately 42 percent of the 45 mg group and 51 percent of the 90 mg group achieved PASI 90 at week 12, compared with approximately 1 percent of patients receiving placebo.
These were the numbers that made the World Congress presentation newsworthy.
Quality-of-Life Results
The trial also examined the effect of treatment on patients' everyday lives through the Dermatology Life Quality Index, commonly abbreviated DLQI.
Improvements were apparent relatively early. By week four, patients receiving either ustekinumab dose had significantly greater improvements in DLQI scores than patients receiving placebo.
By week 12, 72 percent of patients receiving 45 mg and 77 percent receiving 90 mg had achieved a DLQI improvement of at least five points, compared with 21 percent of placebo patients.
Perhaps even more illustrative, 37 percent of patients in the 45 mg group and 39 percent in the 90 mg group reached a DLQI score of zero at week 12. A zero score indicates that the skin disease was reporting no effect on the quality-of-life areas measured by the questionnaire. Only about 1 percent of placebo recipients achieved that result.
For people living with extensive psoriasis, such measurements helped translate changes in skin lesions into a more understandable measure of daily benefit.
Safety Was an Essential Part of the Story
Promising efficacy alone was not sufficient for a new immune-modifying biologic. Safety was a major issue.
During the placebo-controlled first 12 weeks of PHOENIX 2, overall adverse-event rates were broadly similar among the treatment groups. Approximately 49 percent of placebo recipients experienced at least one adverse event, compared with 53 percent of the 45 mg ustekinumab group and 48 percent of the 90 mg group.
Those early findings attracted attention because biologic therapies necessarily raised questions about infection and other consequences of altering immune pathways.
Later regulatory evaluation appropriately examined safety over a much broader evidence base and longer period than could be established by the initial 12-week comparison. When the FDA eventually approved Stelara, the agency required risk-management measures and postmarketing surveillance addressing such concerns as serious infections, malignancies and other potentially important adverse outcomes.
Consequently, the encouraging safety results announced through the 2007 campaign should be understood as early clinical-trial findings rather than a final statement about the drug's lifetime safety profile.
Reaction From Dermatology and the Medical Press
The presentation did not remain confined to CNTO1275WCD.com.
Medical and biotechnology publications reported the findings, while dermatology trade coverage discussed ustekinumab as a potentially important new-generation biologic. Dermatology Times, for example, reported on PHOENIX 2 after the Buenos Aires meeting and specifically noted that investigators Craig Leonardi and Kristian Reich discussed the results during a live Centocor-sponsored press-conference webcast.
The story also circulated among psoriasis patients and online discussion groups. Patients familiar with drugs such as Enbrel, Remicade and Humira began discussing the possibility of a treatment aimed at a different immune pathway and requiring relatively infrequent injections.
Financial analysts also had reason to pay attention. A successful new biologic could alter competition within the psoriasis market. Thus CNTO1275WCD.com's intended audience extended beyond physicians and patients to include journalists, healthcare-industry observers and investment analysts.
The People Behind the 2007 Webcast
The webcast brought together several perspectives rather than relying exclusively on a corporate spokesperson.
Craig Leonardi, MD, of St. Louis University Medical School, was a lead investigator associated with the study. Kristian Reich, MD, of Georg-August University in Göttingen, Germany, also participated.
Silvia Fernandez Barrio represented the patient perspective as executive director of the Civil Association of Psoriasis Patients of Argentina. Tom Schaible, PhD, vice president of Medical Affairs at Centocor, represented the company developing the therapy.
This combination was significant. The webcast could address clinical data, scientific interpretation, the lived burden of psoriasis and the pharmaceutical-development perspective in the same media event.
From CNTO 1275 to Stelara
The greatest historical significance of CNTO1275WCD.com becomes apparent when the story is followed beyond October 2007.
The PHOENIX 2 findings were subsequently published in The Lancet in May 2008. The peer-reviewed publication reported 52-week results and provided the medical community with a much fuller analysis than could be delivered in an initial conference presentation.
Centocor submitted its U.S. Biologics License Application for ustekinumab in late 2007. In June 2008, an FDA advisory committee unanimously recommended approval for treatment of adults with moderate-to-severe plaque psoriasis.
The path to approval was not instantaneous. FDA reviewers considered questions involving long-term immunosuppression, safety monitoring and risk management. A Complete Response letter was issued in December 2008, and additional regulatory work followed.
On September 25, 2009 — almost exactly two years after Centocor's September 25, 2007 announcement of the World Congress presentation — the FDA approved ustekinumab under the brand name Stelara for adults with chronic moderate-to-severe plaque psoriasis who were candidates for phototherapy or systemic therapy.
Thus the experimental “CNTO 1275” represented in the domain name became an approved medicine.
A Website With a Very Narrow but Important Audience
CNTO1275WCD.com was never designed to compete for mass consumer traffic in the way a news portal or consumer health website might.
Its likely peak relevance was concentrated into an exceptionally short period surrounding the September 25 announcement and October 3, 2007 presentation and webcast. Its principal audience consisted of dermatologists, researchers, medical journalists, pharmaceutical analysts, investors, psoriasis advocacy representatives and others following development of biologic therapies.
No reliable historical public traffic figures have surfaced that would justify assigning the domain a specific visitor count or popularity ranking. Its importance is therefore better measured by the event it supported and the subsequent importance of the drug than by conventional website popularity.
Likewise, there is no evidence that CNTO1275WCD.com itself received website awards or accumulated the type of consumer reviews associated with businesses, restaurants or consumer services. Its visibility came through citations and references in press releases, medical coverage and discussions of the trial.
What Visitors Would Have Expected to Find
Unlike a large pharmaceutical website with extensive permanent navigation, CNTO1275WCD.com was event-oriented. Contemporary announcements establish that its most important practical function was registration and access for the October 3 press briefing and webcast.
Its subject matter revolved around CNTO 1275, the Phase 3 results, psoriasis and the World Congress presentation. It should therefore be understood as a campaign or event microsite rather than a broad information architecture with extensive permanent “menus” in the conventional sense.
This distinction is useful when evaluating the domain historically. The narrowness of the name was intentional: a visitor seeing “CNTO1275WCD” in 2007 and familiar with the development program would immediately encounter both the investigational compound designation and the initials of the medical congress around which the website had been created.
Cultural and Medical Significance
CNTO1275WCD.com has significance beyond the survival of an obscure pharmaceutical domain.
It documents a transitional era in both psoriasis treatment and medical communications.
Scientifically, the site sits at the point when targeting IL-12 and IL-23 was moving from an experimental concept toward a validated therapeutic strategy. The strong Phase 3 response demonstrated at the 2007 congress helped establish the clinical importance of this pathway.
For patients, the development represented another step in the transformation of severe psoriasis treatment. Biologic medicines were changing expectations from partial symptom management toward the possibility of substantial or near-complete skin clearance for many patients.
From an internet-history perspective, the site illustrates how pharmaceutical companies were beginning to extend major medical-conference announcements to a worldwide audience through dedicated webcasts. The scientific meeting still occurred in a physical venue in Buenos Aires, but its important findings could simultaneously reach journalists and analysts elsewhere.
Why CNTO1275WCD.com Is Worth Remembering
Most short-lived promotional and event websites disappear once their campaign ends. CNTO1275WCD.com is valuable precisely because its name remains attached to a very specific moment.
In October 2007, ustekinumab was not yet Stelara. Its developers were presenting pivotal Phase 3 evidence, dermatologists were evaluating a different therapeutic target, patients were watching the evolution of biologic treatment, and regulators had not yet decided whether the drug should reach the market.
Two years later, the FDA approved it.
That sequence gives the domain an unusually clear historical arc: experimental compound, international scientific presentation, live webcast, peer-reviewed publication, regulatory evaluation and eventual approval.
CNTO1275WCD.com therefore represents more than an old drug website. It is a digital artifact from the development of a biologic therapy and from an era when dedicated conference microsites and live webcasts were becoming part of the way major pharmaceutical research findings were communicated.
For researchers examining the history of psoriasis treatment, pharmaceutical communications, monoclonal-antibody development or early medical webcasting, the domain provides a useful marker for one of ustekinumab's most important public milestones.