SIMPONI® (golimumab) Gains Positive Opinion from Committee for Medicinal Products for Human Use (CHMP) for the Treatment of Non-Radiographic Axial Spondyloarthritis

News provided by

May 26, 2015, 06:33 ET

KENILWORTH, New Jersey, May 26, 2015 /PRNewswire/ --

MSD Logo (PRNewsFoto/Merck Sharp _ Dohme)

MSD, known as Merck & Co., Inc. in the United States and Canada,- today announced that SIMPONI^®(golimumab) has received CHMP positive opinion for the treatment of adult patients with severe, active non-radiographic axial spondyloarthritis (nr-axial SpA) with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence, who have had an inadequate response to, or are intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs).^[¹^] Once the EU commission issues their EC decision, and if approved, nr-axial SpA patients can be considered for the once-monthly subcutaneous injection with SIMPONI^® (golimumab).

(Logo: http://photos.prnewswire.com/prnh/20141215/720768 )

The CHMP positive opinion was based on the findings from the GO-AHEAD study, which demonstrated significant clinical improvement in patients with active nr-axial SpA treated with golimumab, compared with patients treated with placebo, over 16 weeks.^[²^]

"The indication of SIMPONI^® in non-radiographic axial spondyloarthritis will add to a number of existing indications in rheumatology and gastroenterology," explains Dr Sean Curtis, VP, Immunology Clinical Research at MSD. "Physicians will have an option to help address the treatment needs of a significant group of their patients."

The term Axial Spondyloarthritis (axial SpA), which encompasses both nr-axial SpA and ankylosing spondylitis (AS),^[³^] is a painful and potentially progressive condition that mainly affects the spine and pelvic joints, commonly characterised by chronic lower back pain and stiffness.^[⁴^] The burden of disease in nr-axial SpA is similar to AS.^[⁵^]

Once approved, SIMPONI^® will become available as a treatment option for patients with severe active nr-axial SpA. This will add to the existing approved indications in rheumatology: AS, psoriatic arthritis (PsA) and rheumatoid arthritis (RA). SIMPONI^® is also approved for the treatment of ulcerative colitis.^[⁶^]

Notes to Editors:

About GO-AHEAD

GO-AHEAD was a Phase 3b double-blind, randomized, placebo-controlled trialconducted in patients 18 to 45 years of age with active nr-axial SpA, diagnosed according to the ASessment in Ankylosing Spondylitis (ASAS) criteria.^[²^]

The study evaluated 197 patients who were treated with either golimumab 50 mg (n=97) or placebo (n=100) subcutaneous injections every four weeks. The mean patient age was 31 years and more than half of the patients were male (57 percent). The primary endpoint of the study was the percentage of patients who attained ASAS20 at week 16. Key secondary endpoints included percentage of patients attaining ASAS40, ASAS partial remission, and Bath AS Disease Activity Index (BASDAI) 50; and change from baseline in sacroiliac joint inflammation on MRI (SPondyloArthritis Research Consortium of Canada [SPARCC] score).^[²^]

The study also assessed a subgroup of patients who showed objective signs of inflammation (OSI) by MRI or elevated C-reactive protein (CRP) at baseline. This subset of patients comprised approximately 80 per cent of the total population.^[²^]

About Axial Spondyloarthritis

Axial spondyloarthritis is a painful and potentially progressive form of inflammatory arthritis that mainly affects the spine and pelvic joints, and most commonly results in chronic lower back pain.^[⁴^] It typically begins in the late teens and early twenties and in severe cases can result in complete fusion of the spinal vertebrae and cause structural damage to hips and other joints.^[⁴^] The term axial spondyloarthritis covers both non-radiographic axial spondyloarthritis and ankylosing spondylitis.^[³^] In patients with nr-axial SpA, patients experience symptoms but damage to the joints does not fulfill the modified New York Criteria for AS on X-ray.^[⁷^] The burden of disease in nr-axial SpA is similar to AS.^[⁴^] A proportion of these nr-axial SpA patients may progress to ankylosing spondylitis with typical radiographic changes.^[⁸^] Often misdiagnosed as "just back pain" in the early stages,^[⁵^] axial spondyloarthritis is a systemic inflammatory disease that, in addition to its effect on the spine, can affect other areas such as peripheral joints, eyes, and the bowel.^[⁴^]

About SIMPONI^®(golimumab)

SIMPONI^® is a human monoclonal antibody that targets and neutralises tumour necrosis factor (TNF)-alpha, a protein that when overproduced in the body due to chronic inflammatory diseases can cause inflammation and damage to bones, cartilage and tissue. Licensed indications for golimumab include: moderate to severe, active RA in adults, in combination with methotrexate, when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including methotrexate has been inadequate; severe, active and progressive RA, in combination with methotrexate, in adults not previously treated with methotrexate; active and progressive PsA in adult patients, alone or in combination with methotrexate, when the response to previous DMARD therapy has been inadequate; and severe, active ankylosing spondylitis in adults who have responded inadequately to conventional therapy. Once approved, SIMPONI^®will be indicated for the treatment of adults with severe, active nr-axial SpA with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence, who have had an inadequate response to, or are intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs).

Golimumab is also the first and only subcutaneous anti-tumor necrosis factor (TNF)-alpha treatment administered as an every-four-week maintenance therapy for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy, including corticosteroids and 6-mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications for such therapies. Golimumab is available either through the SmartJect^® autoinjector/prefilled pen or a prefilled syringe as a SC administered injection.^[⁶^]

Janssen Biotech, Inc. discovered and developed SIMPONI^® and markets the product in the United States. The Janssen Pharmaceutical Companies market SIMPONI^® in Canada, Central and South America, the Middle East, Africa and Asia Pacific.

In Japan, Indonesia, and Taiwan, Janssen Biotech, Inc. licenses distribution rights to SIMPONI^® to Mitsubishi Tanabe Pharma Corporation. In Europe, Russia and Turkey, Janssen Biotech, Inc. licenses distribution rights for SIMPONI^® to Schering-Plough (Ireland) Company, a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA.

Please refer to the Summary of Product Characteristics for full information on 'SIMPONI^®' including contraindications, precautions, special warnings and side effects. Available from:

http://www.medicines.org.uk/emc/medicine/23766

Important Safety Information

In the European Union, SIMPONI is contraindicated in patients with active tuberculosis, severe infections such as sepsis, opportunistic infections, in patients with moderate or severe heart failure (NYHA Class III/IV), as well as in patients who are hypersensitive to SIMPONI or any of its excipients. Serious infections, including sepsis, pneumonia, tuberculosis, invasive fungal and other opportunistic infections have been observed with the use of TNF antagonists including SIMPONI. Some of these infections have been fatal. SIMPONI should not be given to patients with a clinically important, active infection. Caution should be exercised when considering the use of SIMPONI in patients with a chronic infection or a history of recurrent infection. Patients should be monitored for signs and symptoms of infection before, during and for several months after treatment with SIMPONI. If a patient develops a new serious infection or sepsis, SIMPONI therapy should be discontinued and appropriate antimicrobial or antifungal therapy should be initiated until the infection is controlled. Patients should be advised of and avoid exposure to potential risk factors for infection as appropriate. For patients who have resided in or traveled to regions where invasive fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic, the benefits and risks of SIMPONI treatment should be carefully considered before initiation of SIMPONI therapy. Patients must be evaluated for the risk of tuberculosis (TB), including latent tuberculosis, prior to initiation of SIMPONI. If active TB is diagnosed, SIMPONI must not be initiated. If latent TB is suspected or diagnosed then the benefit/risk balance of SIMPONI treatment should be considered. Treatment of latent tuberculosis infection should be initiated prior to therapy with SIMPONI.

Antituberculosis therapy prior to initiating SIMPONI should also be considered in patients who have several or significant risk factors for tuberculosis infection and have a negative test for latent tuberculosis, or for patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving SIMPONI should be monitored closely for signs and symptoms of active tuberculosis during and after treatment, including patients who tested negative for latent tuberculosis infections.

The use of TNF blocking agents including SIMPONI has been associated with reactivation of hepatitis B virus in patients who are chronic carriers of the virus. Some of these cases have been fatal. Chronic carriers of hepatitis B should be appropriately evaluated and monitored prior to the initiation of, during treatment with, and for several months following discontinuation of SIMPONI. In patients who develop HBV reactivation, SIMPONI should be discontinued.

Lymphomas have been observed in patients treated with TNF blocking agents, including SIMPONI. The incidence of non-lymphoma malignancies was similar to controls, and lymphoma is seen more often than in the general population. The potential role of TNF-blocking therapy in the development of malignancies is not known. Based on an exploratory clinical trial in patients with COPD, caution should be exercised when using any TNF-blocking therapy in COPD patients, as well as in patients with an increased risk for malignancy due to heavy smoking. Rare post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with other TNF-blocking agents. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal.

Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated with TNF-blocking agents (initiation of therapy ≤ 18 years of age) in the post marketing setting. A risk for the development of malignancies in children and adolescents treated with TNF-blockers cannot be excluded.

It is not known if SIMPONI treatment influences the risk for developing dysplasia or colon cancer. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma, or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before therapy and throughout their disease course.

Melanoma has been reported in patients treated with TNF-blocking agents, including SIMPONI. Periodic skin examination is recommended, particularly for patients with risk factors for skin cancer.

Worsening and new onset congestive heart failure (CHF) and increased mortality due to CHF have been reported with another TNF blocker. SIMPONI has not been studied in patients with CHF. SIMPONI should be used with caution in patients with mild heart failure and must be discontinued if new or worsening symptoms of heart failure appear.

TNF-blocking agents, including SIMPONI, have been associated in rare cases with new onset or exacerbation of demyelinating disorders, including multiple sclerosis. The benefits and risks of anti-TNF treatment should be carefully considered before initiation of SIMPONI therapy in patients with pre-existing or recent onset of demyelinating disorders.

There is limited safety experience of SIMPONI treatment in patients who have undergone surgical procedures, including arthroplasty. A patient who requires surgery while on SIMPONI should be closely monitored for infections, and appropriate actions should be taken.

The possibility exists for TNF-blocking agents, including SIMPONI, to affect host defenses against infections and malignancies. Treatment with SIMPONI may result in the formation of auto-antibodies and, rarely, in the development of a lupus-like syndrome.

There have been postmarketing reports of pancytopenia, leukopenia, neutropenia, aplastic anemia, and thrombocytopenia in patients receiving TNF blockers. Cytopenias including pancytopenia, have been infrequently reported with SIMPONI in clinical trials. Discontinuation of SIMPONI should be considered in patients with significant hematologic abnormalities.

The concurrent administration of TNF-antagonists with anakinra or abatacept is not recommended. Concurrent administration has been associated with increased infections, including serious infections without increased clinical benefit.

Patients treated with SIMPONI may receive concurrent vaccinations, except for live vaccines. Non-serious allergic reactions associated with SIMPONI occurred in clinical trials, and included urticaria, bronchospasm, and hypersensitivity. In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported following SIMPONI administration. Some of these reactions occurred after the first administration of SIMPONI. If an anaphylactic reaction or other serious allergic reactions occur, administration of SIMPONI should be discontinued immediately and appropriate therapy initiated.

The needle cover on the syringe in the pre-filled pen is manufactured from dry natural rubber containing latex, and may cause allergic reactions in individuals sensitive to latex. SIMPONI also contains sorbitol; patients with rare hereditary problems of fructose intolerance should not take SIMPONI. All patients should be monitored for anaphylactic or other serious allergic reactions.

Patients should be given detailed instructions on how to administer SIMPONI. After proper training, patients may self inject if their physician determines that this is appropriate. The full amount of SIMPONI should be administered at all times. Mild injection site reactions commonly occur. In case of severe reaction(s) SIMPONI should be discontinued.

Women of childbearing potential must use adequate contraception to prevent pregnancy and continue its use for at least six months after the last SIMPONI treatment. Women must not breastfeed during and for at least six months after SIMPONI treatment.

The most common adverse reaction reported from the controlled period of pivotal trials was upper respiratory tract infection (12.6 percent of SIMPONI-treated patients compared with 10.7 percent in control-treated patients). In the controlled period of pivotal trials, 5.1 percent of SIMPONI treated patients had injection site reactions compared with 2.0 percent in control-treated patients. The majority of the injection site reactions were mild and moderate, and the most frequent manifestation was injection site erythema.

The SIMPONI Patient Alert Card provides safety information to the patient. It should be given and explained to all patients before treatment. Patients must show the Alert Card to any doctor involved in his/her treatment, during and up to six months after SIMPONI treatment.

For complete EU prescribing information, please visit http://www.ema.europa.eu.

About MSD

Today's MSD, known as Merck (NYSE: MRK) in the United States and Canada, is a global healthcare leader working to help the world be well. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit http://www.msd.com and connect with us on Twitter, Facebook and YouTube.

MSD/Merck Forward-Looking Statement

This news release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck's 2014 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (http://www.sec.gov).

References

Committee for Medicinal Products for Human Use. Summary of opinion (post authorisation): Simponi. Available at: http://www.ema.europa.eu/ema/pages/includes/document/open_document.jsp?webContentId=WC500187055. Accessed May 2015.
J.Sieper et al. A Randomized, Double-Blind, Placebo-Controlled, 16-Week Study of Subcutaneous Golimumab in Patients with Active Nonradiographic Axial Spondyloarthritis. Abstract 2938. American College of Rheumatology, Boston, 15-19 November, 2014 http://acrabstracts.org/abstracts/a-randomized-double-blind-placebo-controlled-16-week-study-of-subcutaneous-golimumab-in-patients-with-active-nonradiographic-axial-spondyloarthritis/ Accessed May 2015.
National Anklyosing Spondylitis society website. Available at: http://nass.co.uk/. Accessed May 2015.
American College of Rheumatology (ACR). Spondylarthritis (Spondylarthropathy) website. Available at: https://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Spondylarthritis_(Spondylarthropathy)/. Accessed April 2015.
Kiltz U et al. Do patients with non-radiographic axial spondyloarthritis differ from patients with ankylosing spondylitis? Arthritis Care Res. 2012 Sep;64(9):1415-1422.
SIMPONI. Summary of product characteristics. Available at: http://www.medicines.org.uk/emc/medicine/23766. Accessed May 2015.
Colbert RA. Early axial spondyloarthritis Curr Opin Rheumatol. 2010 Sep; 22(5): 603-607.
Poddubnyy D et al. Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis. Ann Rheum Dis. 2011;70(8):1369-1374.