RINVOQ® ▼(upadacitinib) Granted EU Marketing Authorisation for the Treatment of Eligible Adults with Moderate to Severe Active Rheumatoid Arthritis

-         Marketing authorisation supported by data from the pivotal Phase 3 SELECT rheumatoid arthritis programme evaluating nearly 4,400 patients^1-5

-         In five pivotal Phase 3 studies, upadacitinib met all primary and ranked secondary endpoints across a variety of adult patient populations with moderate to severe active rheumatoid arthritis^1-5

-         Upadacitinib offered patients improved rates of clinical remission* or low disease activity** compared to treatment with placebo; methotrexate monotherapy; and adalimumab plus methotrexate ^1-5

-         An estimated 400,000 people in the UK are living with rheumatoid arthritis, the majority of whom don’t achieve remission ^6,7

MAIDENHEAD, UK, 18 December, 2019 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced that the European Commission (EC) has granted marketing authorisation for RINVOQ^® (upadacitinib), a once-daily selective and reversible JAK inhibitor, for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). Upadacitinib may be used as monotherapy or in combination with methotrexate (MTX).

 

“Over the past two decades important advances in the treatment of rheumatoid arthritis have been made, making clinical remission a possibility for more people living with rheumatoid arthritis”, said Alice Butler, UK Medical Director, AbbVie. “We are proud to have been at the forefront of this and to now be able to offer people with moderate to severe RA a new oral treatment option.”

 

The EC authorisation of upadacitinib was supported by data from the global Phase 3 SELECT rheumatoid arthritis programme, which evaluated nearly 4,400 patients with moderate to severe active rheumatoid arthritis in five pivotal studies: SELECT-NEXT, SELECT-BEYOND, SELECT-MONOTHERAPY, SELECT-COMPARE and SELECT-EARLY.^1-5 The studies include assessments of efficacy, safety and tolerability across a variety of patients, including those who failed or were intolerant to biologic disease-modifying anti-rheumatic drugs and who were naïve or inadequate responders to MTX.^1-5

 

 

*assessed by DAS28-CRP<2.6 and CDAI≤2.8

**assessed by DAS28-CRP≤3.2

 

“In the SELECT programme upadacitinib has shown notable consistency in efficacy in clinical trials of patient populations from across the globe”, said Prof Andrew Cope, Head of the Centre for Rheumatic Diseases at King’s College London. “The results of these studies mean that patients with active disease have another treatment option with an acceptable safety profile that may induce disease remission even when they have had an inadequate response to drugs such as methotrexate or anti-TNF therapy. Upadacitinib can be used as a single agent and so could benefit many patients who have struggled to tolerate alternative therapies”.

 

Highlights from the Phase 3 SELECT rheumatoid arthritis programme

 

Across the SELECT Phase 3 studies, upadacitinib met all primary and ranked secondary endpoints. Notably, upadacitinib demonstrated consistent efficacy with or without methotrexate and achieved consistent remission* rates across patient populations studied.^1-4

 

Highlights included:

• In SELECT-COMPARE, upadacitinib plus MTX (n=651) demonstrated significantly higher remission rates* versus placebo plus MTX (n=651) (29 percent vs. 6 percent at week 12; p≤0.001) and HUMIRA^® (adalimumab) plus MTX (n=327) (29 percent vs 18 percent at week 12; nominal p≤0.001).⁴
• More patients treated with upadacitinib alone (n=217) achieved remission* than MTX (n=216) in SELECT-MONOTHERAPY (28 percent vs 8 percent at week 14; p≤0.0001) and in SELECT-EARLY (48 percent vs 19 percent at week 24; p≤0.001) (n=317 and 314 respectively).^3,5
• In SELECT-EARLY upadacitinib monotherapy (n=317) demonstrated significant inhibition of structural damage***compared to methotrexate (n=314) (0.1 vs 0.7 at week 24; p≤0.01). Upadacitinib +MTX (n=651) also demonstrated significant inhibition of joint damage*** when compared to placebo + MTX (n=651) in SELECT-COMPARE (0.2 vs 0.9 at week 26; p≤0.001).^4,5

• The most commonly reported adverse drug reactions were upper respiratory tract infections (13.5 percent), nausea (3.5 percent), increased blood creatine phosphokinase (2.5 percent) and cough (2.2 percent). The most common serious adverse reactions were serious infections.^1-5

 

More information on these trials can be found at www.clinicaltrials.gov (NCT02706847, NCT03086343, NCT02629159, NCT02706873, NCT02706951).

 

Earlier this year, upadacitinib received authorisation from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to MTX.

 

About upadacitinib in the European Union⁸

 

Upadacitinib is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more

 

*assessed by DAS28-CRP<2.6 and CDAI≤2.8

*** as measured by modified total Sharp score from baseline

 

disease-modifying anti-rheumatic drugs (DMARDs). Upadacitinib may be used as monotherapy or in combination with methotrexate.

 

Important EU safety information⁸

 

Upadacitinib is contraindicated in patients hypersensitive to the active substance or to any of the excipients, in patients with active tuberculosis (TB) or active serious infections, in patients with severe hepatic impairment, and during pregnancy. Use in combination with other potent  Immunosuppressants is not recommended.

 

Serious and sometimes fatal infections have been reported in patients receiving upadacitinib. The most frequent serious infections reported included pneumonia and cellulitis. Cases of bacterial meningitis have been reported. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis have been reported with upadacitinib. Prior to initiating upadacitinib, consider the risks and benefits of treatment in patients with chronic or recurrent infection or with a history of a serious or opportunistic infection, in patients who have been exposed to TB or have resided or travelled in areas of endemic TB or endemic mycoses, and in patients with underlying conditions that may predispose them to infection. Upadacitinib therapy should be interrupted if a patient develops a serious or opportunistic infection. As there is a higher incidence of infections in patients ≥ 75 years of age, caution should be used when treating this population.

 

Patients should be screened for TB before starting upadacitinib therapy. Anti-TB therapy should be considered prior to initiation of upadacitinib in patients with previously untreated latent TB or in patients with risk factors for TB infection.

 

Viral reactivation, including cases of herpes zoster, were reported in clinical studies. Consider interruption of therapy if a patient develops herpes zoster until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed before starting and during therapy with upadacitinib.

 

The use of live, attenuated vaccines during, or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunisations, including prophylactic zoster vaccinations, prior to initiating upadacitinib, in agreement with current immunisation guidelines.

 

The risk of malignancies, including lymphoma is increased in patients with rheumatoid arthritis (RA). Immunomodulatory medicinal products may increase the risk of malignancies, including lymphoma. The clinical data are currently limited and long-term studies are ongoing. Malignancies, including non-melanoma skin cancer (NMSC), have been reported in patients treated with upadacitinib. Consider the risks and benefits of upadacitinib treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated NMSC or when considering continuing upadacitinib therapy in patients who develop a malignancy. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

 

Absolute neutrophil count < 1000 cells/mm³, absolute lymphocyte count < 500 cells/mm³, or haemoglobin levels < 8 g/dL were reported in <1% of patients in clinical trials. Treatment should not be initiated, or should be temporarily interrupted, in patients with these haematological abnormalities observed during routine patient management.

 

RA patients have an increased risk for cardiovascular disorders. Patients treated with upadacitinib should have risk factors (e.g., hypertension, hyperlipidaemia) managed as part of usual standard of care. Upadacitinib treatment was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined.

 

Treatment with upadacitinib was associated with an increased incidence of liver enzyme elevation compared to placebo. If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, upadacitinib therapy should be interrupted until this diagnosis is excluded.

 

Events of deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors, including upadacitinib. Upadacitinib should be used with caution in patients at high risk for DVT/PE. Risk factors that should be considered in determining the patient’s risk for DVT/PE include older age, obesity, a medical history of DVT/PE, patients undergoing major surgery, and prolonged immobilisation. If clinical features of DVT/PE occur, upadacitinib treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.

 

The most commonly reported adverse drug reactions are upper respiratory tract infections (13.5%), nausea (3.5%), increased blood creatine phosphokinase (2.5%), and cough (2.2%). The most common serious adverse reactions were serious infections.

 

▼Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to AbbVie on UK_PVVendor@abbvie.com.

 

This is not a complete summary of all safety information. See upadacitinib full summary of product characteristics (SmPC) at https://www.ema.europa.eu/en/medicines/human/EPAR/rinvoq#product-information-section. Globally, prescribing information varies; refer to the individual country product label for complete information.

 

 

About HUMIRA^® (adalimumab) in the European Union⁹

Adalimumab, in combination with methotrexate, is indicated for the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying anti-rheumatic drugs, including methotrexate, has been inadequate.

 

 

 

Important EU safety information⁹

Adalimumab is contraindicated in patients with active tuberculosis or other severe infections such as sepsis, and opportunistic infections and in patients with moderate to severe heart failure (NYHA class III/IV). It is also contraindicated in patients hypersensitive to the active substance or to any of the excipients; serious allergic reactions including anaphylaxis have been reported. The use of adalimumab increases the risk of developing serious infections which may, in rare cases, be life-threatening. Rare cases of lymphoma and leukemia have been reported in patients treated with adalimumab. On rare occasions, a severe type of cancer called hepatosplenic T-cell lymphoma has been observed and often results in death. A risk for the development of malignancies in patients treated with TNF-antagonists cannot be excluded. Rare cases of pancytopenia, aplastic anaemia, demyelinating disease, lupus, lupus-related conditions and Stevens-Johnson syndrome have been reported in patients treated with adalimumab. The most frequently reported adverse events across all indications included respiratory infections, injection site reactions, headache and musculoskeletal pain.

 

This is not a complete summary of all safety information. Please see the full SmPC for complete prescribing information at https://www.ema.europa.eu/en/medicines/human/EPAR/humira#product-information-section. Globally, prescribing information varies; refer to the individual country product label for complete information.

 

 

About AbbVie

 

AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world’s most complex and critical conditions. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.co.uk . Follow @abbvieuk on Twitter

 

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UK Media:   Natalie Bennett AbbVie T: 07818 428074 E: natalie.bennett@abbvie.com

Becky Wright Four Health Communications T:020 3761 4495 E:Becky.Wright@fourhealthcommunications.com

 

References

1.       Burmester GR, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Jun 23;391(10139):2503-2512. doi: 10.1016/S0140-6736(18)31115-2. Epub 2018 Jun 13.

2.       Genovese MC, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet. 2018 Jun 23;391(10139):2513-2524. doi: 10.1016/S0140-6736(18)31116-4. Epub 2018 Jun 13.

3.       Smolen JS, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet. 2019. May 23. pii: S0140-6736(19)30419-2. doi: 10.1016/S0140-6736(19)30419-2. Epub 2019 May 23.

4.       Fleischmann R, et al. Upadacitinib versus Placebo or Adalimumab in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double‐Blind, Randomized Controlled Trial: Arthritis and Rheumatology. 2019. Jul 9; 71 (11):1788-1800

5.       van Vollenhoven R, et al. A Phase 3, Randomized, Controlled Trial Comparing Upadacitinib Monotherapy to MTX Monotherapy in MTX-Naïve Patients with Active Rheumatoid Arthritis. 2018 ACR/ARHP Annual Meeting; 891.

6.       NICE. Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed (TA375). January 2016

7.       Bergstra SA et al. Inequity in access to bDMARD care and how it influences disease outcomes across countries worldwide: results from the METEOR-registryAnn Rheum Dis. 2018; 77:1413-1420

8.       RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co KG.

9.       HUMIRA [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co KG. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000481/WC500050870.pdf. Accessed November 12, 2019.