NORTH CHICAGO, Ill., June 10, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced new data from a Phase 2a study of ABBV-3373, an investigational anti-tumor necrosis factor (TNF) Glucocorticoid Receptor Modulator (GRM) steroid antibody drug conjugate (ADC), in adult patients with moderate to severe rheumatoid arthritis.1 The primary endpoint was the change in Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) from baseline to week 12 and two statistical comparisons were pre-specified.1 The first compared ABBV-3373 and mean outcome from historical adalimumab data.1 The second compared ABBV-3373 and combined in-trial and historical adalimumab data.1 Results of the first comparison show a greater difference in the primary endpoint change in DAS28-CRP from baseline to week 12 for ABBV-3373 (-2.65) as compared to a pre-specified historical adalimumab mean (-2.13) (p=0.022).1 Results of the second comparison, based on a Bayesian analysis, predicted with a 90 percent probability that ABBV-3373 was associated with a greater improvement on DAS28-CRP from baseline to week 12 than adalimumab based on in-trial data combined with historical data.1 Additionally, evaluations of serum cortisol levels over 12 weeks indicate that ABBV-3373 showed no systemic glucocorticoid effects.1
"This proof of concept study demonstrates clinical activity of the TNF-ADC platform and its potential to advance the standard of care for patients with rheumatoid arthritis," said Michael Severino, M.D., vice chairman and president, AbbVie. "Based on these results we will advance the development of the TNF-ADC platform in rheumatoid arthritis and begin clinical studies in other immune-mediated diseases."
These are the first results to be reported for the novel ADC in rheumatoid arthritis. ABBV-3373 is an investigational medicine that is not approved by regulatory authorities and is being studied for the treatment of rheumatoid arthritis and other immune-mediated diseases.1,2 Full results from this study will be presented at an upcoming medical meeting and/or published in a peer-reviewed publication.
In the 31 rheumatoid arthritis patients on ABBV-3373 and 17 rheumatoid arthritis patients on adalimumab, in the trial, the safety profile of ABBV-3373 was generally similar to adalimumab.1 The overall adverse events (AE) rate of ABBV-3373 was lower than adalimumab (35 percent [n=11] vs. 71 percent [n=12], respectively).1 The AEs occurring in ≥5 percent of patients were urinary tract infections, with two events in each treatment group, and headache, with two events in the ABBV-3373 group and one event in the adalimumab group.1 Six percent (n=1) of subjects treated with adalimumab and three percent (n=1) of subjects treated with ABBV-3373 discontinued treatment due to an AE.1 Through week 12, serious adverse events (SAEs) occurred in four patients in the ABBV-3373 group (13 percent, [n=4]), compared to none in the adalimumab group (0 percent, [n=0]).1 In the ABBV-3373 group, two SAEs were deemed unrelated to study drug (pneumonia and upper respiratory tract disease).1 One SAE was non-cardiac chest pain and one SAE was reported as anaphylactic shock; this subject fully recovered and no further events of hypersensitivity were reported after drug administration time was extended for subsequently dosed subjects.1
Being developed by AbbVie, ABBV-3373 is an investigational ADC comprised of a novel glucocorticoid receptor modulator (GRM) linked to adalimumab, and aims at modulating TNF-mediated inflammatory pathways by delivering a glucocorticoid payload directly into activated immune cells expressing membrane bound TNF. This ADC was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side-effects associated with glucocorticoids. ABBV-3373 is an investigational medicine that is not approved by regulatory authorities and is being studied for the treatment of rheumatoid arthritis and other immune-mediated diseases.
About the M16-560 Study1,2
The M16-560 study is a Phase 2a, multicenter, randomized, double-blind, double-dummy, active-controlled study designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of ABBV-3373 in adult patients with moderate to severe rheumatoid arthritis with an inadequate response to MTX. Patients were randomized in a 2:1 ratio to ABBV-3373 (n=31) at 100 mg, every other week (EOW) or adalimumab (n=17) at 80 mg, EOW for 12 weeks.
Bayesian statistical methods incorporating historical data were used to achieve adequate statistical power in this proof of concept study, which was accomplished through pre-specified supplementation of adalimumab in-trial data with historical adalimumab data for comparison with ABBV-3373 for the primary endpoint analyses. The historical data were obtained from three historical adalimumab trials of similar settings. The primary endpoint was the change in DAS28-CRP from baseline to week 12 and two statistical comparisons were pre-specified. The first compared ABBV-3373 and mean outcome from historical adalimumab data with the success criteria of two-sided p-value ≤0.1. The second compared ABBV-3373 and combined in-trial and historical adalimumab data (success criterion: probability of >95 percent).
Important Safety Information about HUMIRA™ (adalimumab)3
HUMIRA U.S. Use and Important Safety Information
HUMIRA is a prescription medicine used to reduce the signs and symptoms of moderate to severe rheumatoid arthritis in adults. HUMIRA can be used alone, with methotrexate, or with certain other medicines. HUMIRA may prevent further damage to bones and joints and may help the ability to perform daily activities.
HUMIRA is a TNF blocker medicine that affects the immune system and can lower the body's ability to fight infections. Serious infections have happened in people taking HUMIRA. These serious infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some people have died from these infections. People should be tested for TB before HUMIRA use and monitored for signs and symptoms of TB during therapy, even if their TB test was negative. People at risk of TB may be treated with medicine for TB. Treatment with HUMIRA should not be started in a person with an active infection, unless approved by a doctor. HUMIRA should be stopped if a person develops a serious infection. People should tell their doctor if they live in or have been to a region where certain fungal infections are common, as these infections may happen or become more severe if people use HUMIRA. People should tell their doctor if they have had TB or hepatitis B, are prone to infections, or have symptoms such as fever, fatigue, cough, or sores.
For people taking TNF blockers, including HUMIRA, the chance of getting lymphoma or other cancers may increase. Some people have developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. If using TNF blockers, including HUMIRA, the chance of getting two types of skin cancer (basal cell and squamous cell) may increase. These types are generally not life-threatening if treated.
Other possible serious side effects with HUMIRA include hepatitis B infection in carriers of the virus; allergic reactions; nervous system problems; blood problems; certain immune reactions, including a lupus-like syndrome; liver problems; and new or worsening heart failure or psoriasis. The use of HUMIRA with anakinra or abatacept is not recommended. People using HUMIRA should not receive live vaccines. Children should be brought up to date on all vaccines before starting HUMIRA.
Common side effects of HUMIRA include injection site reactions (redness, rash, swelling, itching, or bruising), upper respiratory infections (including sinus infections), headaches, rash, and nausea.
HUMIRA is given by injection under the skin.
The benefits and risks of HUMIRA should be carefully considered before starting therapy.
Please click here for the Full Prescribing Information and Medication Guide.
This is the most important information to know about HUMIRA. For more information, talk to your HCP.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088
About AbbVie in Rheumatology
For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Our longstanding commitment to discovering and delivering transformative therapies is underscored by our pursuit of cutting-edge science that improves our understanding of promising new pathways and targets in order to help more people living with rheumatic diseases reach their treatment goals. For more information on AbbVie in rheumatology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/rheumatology.html.
AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2019 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
- AbbVie. Data on File: ABVRRTI70670.
- A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 and ABBV-154 in Participants With Moderate to Severe Rheumatoid Arthritis. 2020. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03823391. Accessed on June 9, 2020.
- HUMIRA (adalimumab) [Package Insert]. North Chicago, Ill.: AbbVie Inc.