Replies to post #84135 on Biotech Values

[DewDiligence]

JNJ Psoriasis Drug Wins FDA Approval

http://www.reuters.com/article/marketsNews/idCNN2552238720090925

›Fri Sep 25, 2009 5:33pm EDT
By Ransdell Pierson

NEW YORK, Sept 25 (Reuters) - Johnson & Johnson said on Friday U.S. regulators approved its new treatment for psoriasis, called Stelara, for patients 18 years or older with moderate to severe psoriasis.

Stelara, deemed a potential blockbuster because of its effectiveness and infrequent administration, has been awaiting approval since late 2007. The U.S. Food and Drug Administration had extended its review of the product on several occasions to study amendments to J&J's marketing application and to review other information.

"Stelara's main advantage is its more-convenient dosing," said Wells Fargo analyst Larry Biegelsen. He noted that it is given by injection only once every three months, compared with injections every few weeks with the leading class of drugs called tumor necrosis inhibitors -- including Abbott Laboratories Inc's (ABT) Humira.

The J&J drug will likely generate sales of $130 million in 2010, growing to more than $500 million in 2013, Biegelsen said.

Psoriasis, in which itchy red plaques accumulate on the surface of the skin, is caused by an overproduction of skin cells. It affects an estimated 7.5 million patients in the United States.

Stelara, whose chemical name is ustekinumab, is a monoclonal antibody that proved superior to Amgen Inc's (AMGN) and Wyeth's (WYE) injectable Enbrel in one study. It works by taming two immune system proteins called interleukin-12 (IL-12) and interleukin-23 (IL-23) that are linked to inflammation.

It was well tolerated in large studies, with generally mild side effects that did not require adjustments in the medicine. But J&J cautioned on Friday that some serious infections have been linked to the drug and that it may increase the risk of cancer.

Current treatments -- including Enbrel, Humira and J&J's older Remicade medicine that is given by intravenous infusion -- can also increase risk of infection.‹

[DewDiligence]

For JNJ, which has endured a spate of bad publicity recently,
Stelara is one of the bright spots. (Note: etanercept=Enbrel.)

http://finance.yahoo.com/news/STELARATM-ustekinumab-Shows-prnews-3755316998.html?x=0&.v=1

›Stelara™ (ustekinumab) Shows Greater Efficacy Than Etanercept for Treatment of Moderate to Severe Plaque Psoriasis

January 14, 2010, 3:00 am EST

HIGH WYCOMBE, England, January 14 /PRNewswire/ --

- Results From First Phase III Comparator Study of Biologic Agents in Psoriasis Published Today in New England Journal of Medicine

Findings from a new Phase III study comparing the efficacy and safety of STELARA™(ustekinumab) with etanercept in the treatment of moderate to severe plaque psoriasis, show a significantly higher clinical response with STELARA over a 12-week period compared to high-dose etanercept (50mg twice-weekly). The results of the study, published today in The New England Journal of Medicine, also demonstrate the clinical benefit of STELARA among patients who failed to respond to etanercept.(1)

"This study provides important comparative efficacy information about the treatment of moderate to severe plaque psoriasis with two biologic agents," said Professor Chris Griffiths of the University of Manchester, and lead trial investigator. "We observed a substantial proportion of patients achieving high levels of skin clearance with ustekinumab, both through the study's primary endpoint at week 12 and following crossover from etanercept, including in those patients who showed a lack of response to etanercept during the study."

In the comparator study of 903 patients, 68% and 74% of patients receiving subcutaneous injections of STELARA (45 mg or 90 mg respectively) at weeks 0 and 4 achieved at least a 75 per cent improvement in their psoriasis symptoms as measured by the Psoriasis Area and Severity Index (PASI 75) at week 12, the primary endpoint. This was significantly higher compared to the 57% of patients who achieved PASI 75 receiving the maximum recommended dose for etanercept; subcutaneous injections of 50 mg twice per week for 12 weeks (P = 0.01 for STELARA 45 mg; P < 0.001 for STELARA 90 mg, each compared with etanercept). Onset of clinical response occurred more rapidly among STELARA-treated patients, with higher numbers of patients achieving PASI 75 by week 8 compared with patients receiving etanercept.(1)

Investigators also reported that a greater proportion of patients receiving STELARA achieved a marked improvement in psoriasis as assessed by PASI 90 response, or nearly complete clearance of psoriasis. At week 12, 36% of patients receiving STELARA 45 mg and 45% of patients receiving STELARA 90 mg achieved PASI 90 compared with 23% of patients receiving etanercept (P < 0.001 for each comparison versus etanercept). Moreover, a greater proportion of patients in the STELARA 45 mg and 90 mg treatment groups achieved a Physician Global Assessment (PGA) score of "cleared" or "minimal" (65% and 71% of patients, respectively) compared with patients in the etanercept treatment group (49%; p < 0.001 for each comparison versus etanercept).(1)

Patients who had an inadequate response to etanercept, as measured by PGA score (classified as moderate, marked or severe psoriasis at week 12), received an injection of STELARA 90 mg at weeks 16 and 20. At week 28, investigators reported that nearly half of patients (49%) who failed to respond to etanercept and who crossed over to STELARA achieved PASI 75.(1)

Through week 12 of the study, the percentage of study participants experiencing at least one adverse event (AE) was comparable between the STELARA 45 mg group (66%), the STELARA 90 mg group (69%) and the etanercept 50 mg group (70%). The proportion of patients experiencing at least one serious AE through week 12 were as follows: 1.9% and 1.2% of patients receiving STELARA 45 mg or 90 mg, respectively, compared with 1.2% of patients receiving etanercept. Rates of specific AEs were generally comparable between treatment groups with the exception of injection site reactions, which were reported in 25% of patients treated with etanercept versus 4.3% and 3.7% with STELARA 45 mg and 90 mg, respectively. This disparity, however, may have been influenced by the greater number of etanercept injections administered (at least 24 in the 12-week portion of the study) compared with two STELARA injections.(1)

Through week 64, the rates and types of AEs were generally comparable between patients in the 45 mg (87%) and 90 mg (89%) STELARA groups, and also before and after crossover from etanercept to STELARA (79% vs 65%). This was also the case for serious adverse events (3.5% vs 3.4%).(1)

About the ACCEPT Trial

The Phase 3, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Ustekinumab Compared to Etanercept in the Treatment of Subjects with Moderate to Severe Plaque Psoriasis (ACCEPT) included 903 patients with chronic plaque psoriasis (etanercept=347, STELARA 45 mg=209, STELARA 90 mg=347). Patients were randomised to receive subcutaneously administered STELARA or etanercept. Patients randomised to receive STELARA received 45 mg or 90 mg doses at weeks 0 and 4. Patients in the etanercept group received twice-weekly doses of 50 mg for 12 weeks. The primary endpoint of the study was the proportion of patients who achieved PASI 75 at week 12. At week 12, patients in the etanercept group who were classified as non-responders (i.e., had moderate, marked or severe psoriasis) received 90 mg of STELARA at weeks 16 and 20. STELARA non-responders received one additional dose of STELARA at week 16. Treatment was interrupted for all patients who had cleared, minimal or mild psoriasis at the end of week 12, and all patients were re-treated with 45 or 90 mg STELARA when their disease worsened to moderate or worse. The study was sponsored by Centocor Ortho Biotech Inc.

About Psoriasis

Psoriasis is a chronic, immune-mediated inflammatory disease resulting in the over-production of skin cells which accumulate on the surface of the skin, leading to raised, red, scaly plaques that may itch and bleed. It is estimated that 1.5 million people in the UK have psoriasis.(2,3) Twenty to thirty percent of those with psoriasis have severe disease.(4) In addition to the significant impact that psoriasis can have on quality of life,(5) many patients report feeling dissatisfied and frustrated with some existing treatment options which can be inconvenient and time consuming to use.(5)

About STELARA (ustekinumab)

STELARA is a new, human monoclonal antibody with a novel mechanism of action that targets the p40 subunit of the cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23). IL-12 and IL-23 are naturally occurring proteins that are important in regulating immune responses and are thought to be associated with some immune-mediated inflammatory disorders, including plaque psoriasis.

STELARA is licensed for the treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate and PUVA (psoralen plus ultraviolet A light).The recommended dose for STELARA in patients weighing up to 100kg is 45mg at week 0, week 4 and then every 12 weeks thereafter. In patients weighing more than 100kg the dose is 90mg at week 0, week 4 and then every 12 weeks thereafter.(6)

Centocor Ortho Biotech Inc. developed STELARA and has exclusive marketing rights to the product in the United States. Janssen-Cilag has exclusive marketing rights in all countries outside of the United States. Centocor Ortho Biotech and Janssen-Cilag are members of the Johnson & Johnson family of companies.

Important Safety Information

Ustekinumab is a selective immunosuppressant and may have the potential to increase the risk of infections and reactivate latent infections. Serious infections have been observed in patients receiving ustekinumab in clinical trials. Do not start ustekinumab during an active infection. If a serious infection develops, monitor patients carefully and stop ustekinumab until the infection resolves. Patients should be evaluated for tuberculosis (TB) infection prior to initiating, and during, treatment with ustekinumab.

Ustekinumab is a selective immunosuppressant. Immunosuppressive agents have the potential to increase the risk of malignancy. Malignancies have been observed in patients receiving ustekinumab in clinical trials. Caution should be exercised when considering the use of ustekinumab in patients with a history of malignancy or when considering continuing treatment in patients who develop a malignancy.

References

1. Griffiths C, Strober B, van de Kerkhof P et al. Comparison of Ustekinumab and Etanercept for Moderate-to-Severe Psoriasis. N Engl J Med. 2010;362:118-28

2. National Statistics Online. Population size. Available at: http://www.statistics.gov.uk/CCI/nugget.asp?ID=273. Accessed on January 07, 2010.

3. The Psoriasis Association. What is psoriasis? Available at:http://www.psoriasis-association.org.uk/what-is.html. Accessed January 07, 2010.

4. Smith CH, Anstey AV, Barker JN, et al. British Association of Dermatologists guidelines for use of biological interventions in psoriasis 2005. Br J Dermatol. 2005;153(3):486-497.

5. Dubertret L, Mrowietz U, Ranki A, et al. European patient perspectives on the impact of psoriasis: the EUROPSO patient membership survey. Br J Dermatol. 2006;155(4):729-736.

6. Janssen-Cilag Ltd. STELARA 45mg solution for injection. Summary of Product Characteristics (SPC). 16 January 2009.‹

[DewDiligence]

ABT Reports Positive Phase-3 Psoriasis Data for Briakinumab (a/k/a ABT-874)

http://finance.yahoo.com/news/Abbott-Reports-Psoriasis-prnews-1127459263.html?x=0&.v=2

In two of the four phase-3 studies reported in the above PR, Briakinumab was compared to Enbrel and was found to be statsig better at 12 weeks on the co-primary endpoints of PASI 75 and PGA 0/1. These two studies (called M10-114 and M10-315) were clones, so I’ve combined their results in the table below.

 
 Endpoint    Briakinumab  Enbrel  Placebo 
 PASI 75*       81%       48%      7% 
 PGA 0/1‡       72%       35%      4% 

* Psoriasis Area and Severity Index showing >=75% clearance.
‡Physician's Global Assessment of clear or normal.

ABT recently submitted a BLA and European MAA for Briakinumab, which targets the IL-12/23 pathways. If approved, Briakinumab will be a direct competitor of JNJ’s Stelara, which was approved in late 2009 (#msg-41895282) and showed superiority to Enbrel in psoriasis (#msg-45763880). Stelara is dosed every three months while Briakinumab is dosed monthly.