TNF alpha inhibitor (Arthrogen)

- Next-generation and first oral TNF- α inhibitor, which completed Phase 2 study for age-related condition sarcopenia, represents a potentially groundbreaking advance in the treatment of RA and disruption of a $41 billion industry - Acceptance follows statistically significant Phase 2 data in sarcopenia showing MYMD-1 reduced TNF- α and other inflammatory markers common to RA, while demonstrating safety and tolerability - MyMD now advancing 3 clinical programs for MyMD-1 in chronic inflammatory conditions including Sarcopenia, RA and Hashimoto’s Thyroiditis BALTIMORE, MD, USA I August 14, 2023 I MyMD Pharmaceuticals, Inc. ® (Nasdaq: MYMD) (“MyMD” or “the Company”), a clinical stage biopharmaceutical company committed to developing novel therapies for age-related diseases, autoimmune and inflammatory conditions, announced today that the U.S. Food and Drug Administration (FDA) has accepted the Company’s Investigational New Drug Application (IND) to evaluate the safety, efficacy, pharmacodynamics and pharmacokinetics of oral TNF-α inhibitor MYMD-1 ® in patients with active rheumatoid arthritis (RA). The application was based on preclinical data showing that MYMD-1 significantly reduced swelling and other clinical arthritis measures compared to widely used RA therapy, Enbrel® (etanercept). 1 The Company plans to initiate discussions with CRO vendor IQVIA on timing of a Phase 2 study in this indication. MYMD-1 is an oral, next-generation TNF-α inhibitor with the potential to transform the way TNF-α based diseases are treated due to its selectivity and ability to cross the blood brain barrier. Its ease of oral dosing is a significant differentiator compared to currently available TNF-α inhibitors, all of which require delivery by injection or infusion. MYMD-1 has also been shown to selectively block TNF-α action where it is overactivated without preventing it from doing its normal job of responding to routine infection. MYMD-1 is doubly effective at inhibiting inflammation by blocking both TNF-a and IL-6 activity, whereas currently approved anti-TNF and anti-IL-6 treatments for RA can only target one or the other. In addition, in early clinical studies it has not been associated with serious side effects known to occur with traditional immunosuppressive therapies that treat inflammation. “FDA acceptance of an IND in RA for our next-generation oral TNF-α inhibitor, MYMD-1, is our most significant milestone as it adds substantial momentum to our clinical program with sufficient funding and targets one of the largest potential market opportunities,” said Chris Chapman, M.D., president, director, and chief medical officer of MyMD. “We are excited to initiate discussions with our CRO regarding a Phase 2 clinical trial in RA and believe the statistically significant biomarker data from the Phase 2 study in sarcopenia show MYMD-1 has the potential to disrupt the TNF-α inhibitor market and offer therapeutic benefit to patients with a range of chronic inflammatory conditions.” Recently, MyMD announced positive, statistically significant Phase 2 study results in participants with sarcopenia/frailty which showed MYMD-1 reduced TNF-α, IL-6 and sTNFR1, biomarkers which are common to a number of chronic inflammatory diseases, and met all safety and tolerability endpoints. The Company plans to initiate Phase 3 trials. If approved, MYMD-1 has the potential to be the first drug approved by FDA for the sarcopenia, an age-related decline in muscle mass and physical function which leads to greater risk of hospitalization, disability, and death. “This is significant news and suggests MYMD-1 may hold promise to be the first oral TNF-α inhibitor and a potential future treatment for rheumatoid arthritis,” said clinical researcher, rheumatologist and past President of the Florida Society of Rheumatology, Robert W. Levin, MD. “There remains a need for new oral therapies with novel mechanism of action for patients not served by current options and I look forward to leading upcoming Phase 2 studies of MYMD-1 to determine its full potential in RA. I look forward to reviewing the study outcomes.” About Rheumatoid Arthritis Rheumatoid arthritis, an autoimmune disorder characterized by inflammation (painful swelling) and bone erosion, affects nearly 14 million people worldwide, including 1.5 million Americans. 2 Although typically associated with older adults, RA can occur at any age, and it is three times more likely to affect women than men. 3 TNF-α has played a central role in treatments for RA since 1998, all of which are administered via injection or infusion. Furthermore, the burden to patients, care providers and society is striking, with an estimated annual cost of $39.2 billion. 4 The price tag includes healthcare costs, loss of employment, costs to employers, government and caregivers as well as costs associated with a deterioration of quality of life, among other societal costs. About MYMD-1 MYMD-1, a next generation, oral selective inhibitor of tumor necrosis factor-alpha (TNF-α), a driver of chronic inflammation, and this drug is being studied to slow the aging process, prevent sarcopenia and frailty, extend healthy lifespan, as well as treat rheumatoid arthritis. Its ease of oral dosing is a significant differentiator compared to currently available TNF-α inhibitors, all of which require delivery by injection or infusion. MYMD-1 has shown effectiveness in pre-clinical and clinical studies in regulating the immune system. Unlike other therapies, MYMD-1 has been shown in these studies to selectively block TNF-α when it becomes overactivated in autoimmune diseases and cytokine storms, but not block it from doing its normal job of being a first responder to any routine type of moderate infection. In addition, it has not been shown to cause serious side effects common with traditional immunosuppressive therapies that treat inflammation. About MyMD Pharmaceuticals MyMD Pharmaceuticals, Inc. (Nasdaq: MYMD), is a clinical stage biopharma company developing groundbreaking therapies for the treatment of serious and debilitating autoimmune and inflammatory diseases. MyMD’s lead clinical candidate, MYMD-1 ® , is an orally available next-generation TNF-α inhibitor with the potential to transform the way that TNF-α based diseases are treated. MYMD-1 ® , with its small molecule design, improved safety profile and ability to cross the blood brain barrier, has the promise to provide meaningful therapeutic solutions to patients not served by current TNF-α inhibitors and as a potential therapy for CNS-based inflammatory and autoimmune diseases. The company has completed Phase 2 studies of MYMD-1 ® for sarcopenia/frailty, a result of the aging process, as well as early-stage trials for rheumatoid arthritis (RA), with the potential to expand into other applications. MyMD’s second therapeutic candidate is Supera-CBD, a novel, synthetic, non-toxic cannabidiol (CBD) analog that is 8000 times more potent a CB2 agonist (activator) than plant-based CBD. The U.S. Drug Enforcement Administration (DEA)’s scientific review concluded Supera-CBD will not be considered a controlled substance or listed chemical under the Controlled Substances Act (CSA) and its governing regulations or require scheduling during development . In addition to its potential role in managing addiction, anxiety, chronic pain and seizures, Supera-CBD has also been shown to have anti-inflammatory effects. For more information, visit www.mymd.com . 1 ENBREL ETANERCEPT is a registered trademark of Immunex Corporation 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352468/ 3 https://www.arthritis.org/diseases/rheumatoid-arthritis 4 https://pubmed.ncbi.nlm.nih.gov/19908947/ SOURCE: MyMD Pharmaceuticals

- At week 24, upadacitinib 30 mg given alone or as a combination therapy (ABBV-599 high dose [elsubrutinib 60 mg and upadacitinib 30 mg]) met the primary endpoint of systemic lupus erythematosus (SLE) Responder Index (SRI-4) and steroid dose less than or equal to 10 mg prednisone equivalent once per day in patients with moderately to severely active SLE receiving standard lupus therapies 1 - Upadacitinib maintained greater improvements in SLE disease activity at week 48 as measured by the British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA), SRI-4, Lupus Low Disease Activity State (LLDAS) and lupus flares compared with placebo 2 - No new safety signals were observed beyond the known safety profile for upadacitinib. Types of adverse events reported with ABBV-599 high dose were similar to those reported for patients treated with upadacitinib alone 2 - Study results are being presented as an oral presentation at the European Congress of Rheumatology, EULAR 2023 NORTH CHICAGO, IL, USA I May 31, 2023 I AbbVie (NYSE: ABBV) today announced the results of the Phase 2 SLEek study evaluating upadacitinib (RINVOQ ® 30 mg) alone and in combination [ABBV-599 high dose (elsubrutinib 60 mg and upadacitinib 30 mg)] in adults with moderately to severely active systemic lupus erythematosus (SLE) who continued to receive standard lupus therapies. The study results are being presented as an oral presentation during the European Congress of Rheumatology, EULAR 2023. In the Phase 2 SLEek study, a greater proportion of patients receiving upadacitinib 30 mg or ABBV-599 high dose achieved the primary endpoint, SLE Responder Index (SRI-4) and steroid dose less than or equal to 10 mg prednisone equivalent once per day at week 24, compared to placebo (54.8 percent; p=0.028 and 48.5 percent; p=0.081* versus 37.3 percent, respectively). 1 SRI-4 and steroid dose less than or equal to 10 mg prednisone equivalent per day assess reductions in disease activity and glucocorticoid use, respectively. 3 "There are limited treatment options for people living with SLE, leaving physicians challenged on how to effectively slow disease progression and limit potential organ damage in their patients," said Roopal Thakkar, M.D., senior vice president, development and regulatory affairs and chief medical officer, AbbVie. "As a leader in immunology, AbbVie is committed to advancing care in areas of unmet need, such as SLE. We are encouraged by these positive Phase 2 data and look forward to continuing to study upadacitinib for systemic lupus erythematosus in two Phase 3 trials as part of our ongoing clinical program." Key secondary endpoints were also achieved at week 48 in both active treatment groups, including lupus flares measured by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) and time to first flare, which showed greater treatment effect in the upadacitinib 30 mg and ABBV-599 high dose groups compared to placebo. 2 Other measures of disease activity and treatment response were also met, including achievement of BICLA response, SRI-4, and Lupus Low Disease Activity State (LLDAS) in the upadacitinib 30 mg and ABBV-599 high dose groups compared to placebo. 2 SLE—the most common type of lupus—is an autoimmune disease where the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. 4 It can impact the joints, skin, brain, lungs, kidneys and blood vessels, causing a variety of symptoms, including fatigue, skin rashes, fevers, and pain and swelling in the joints. 4 Disease activity in lupus—often called flares—is unpredictable. 5 Flares can appear without warning, come and go and vary in severity—serious flares can cause organ damage and require medical attention. 6 "Lupus is an imbalance in the immune system caused by a diverse set of inherited and environmental factors. It impacts over three million people around the world and causes an overlapping spectrum of symptoms," said Joan Merrill, M.D., Oklahoma Medical Research Foundation, Arthritis & Clinical Immunology Research Program. "To achieve sustainable progress with SLE, we need more treatment options for patients with this disease." No new safety signals were observed beyond the known safety profile for upadacitinib. 2 Types of adverse events reported with ABBV-599 high dose were similar to those reported for patients treated with upadacitinib alone. 2 The rate of treatment emergent adverse events (TEAEs) in this study were similar across groups (ABBV-599 at 86.8 percent, upadacitinib at 82.3 percent and placebo at 78.7 percent). 2 Serious AEs were reported in 10.3 percent of patients in the ABBV-599 high dose, 21.0 percent in upadacitinib 30 mg, and 17.3 percent in placebo groups. 2 Adjudicated cardiovascular events were reported in one patient in each of the three treatment groups. 2 There were no reports of malignancies or venous thromboembolic events. 2 The use of upadacitinib and elsubrutinib in SLE are not approved and their safety and efficacy have not been evaluated by regulatory authorities. About the SLEek Phase 2 Study In the SLEek Phase 2 study, 341 patients undergoing standard lupus therapy were randomized to receive once daily ABBV-599 high dose, ABBV-599 low dose (elsubrutinib 60 mg plus upadacitinib 15 mg), elsubrutinib 60 mg, upadacitinib 30 mg or placebo. 2 After a planned interim analysis when 50 percent of patients reached week 24 or withdrew from the study, the ABBV-599 low dose and elsubrutinib 60 mg arms were discontinued for lack of efficacy. 205 patients continued in the study to week 48 (ABBV-599 HD n = 68, upadacitinib 30 mg n = 62, placebo n = 75). 2 As previously disclosed , AbbVie is advancing its clinical program of upadacitinib in SLE to Phase 3 based on these results. ABBV-599 will not move forward to Phase 3 due to no additional contribution of efficacy by elsubrutinib relative to upadacitinib alone. Additional results from the SLEek study are being presented at EULAR in posters 1133 and 1137. About RINVOQ ® (upadacitinib) Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. 7-20 In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2. 7 The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known. 7 Upadacitinib (RINVOQ) is in Phase 3 development for giant cell arteritis, Takayasu arteritis and systemic lupus erythematosus. 14,18,20 EU Indications and Important Safety Information about RINVOQ ® (upadacitinib) 7 Indications Rheumatoid arthritis RINVOQ is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate. Psoriatic arthritis RINVOQ is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs. RINVOQ may be used as monotherapy or in combination with methotrexate. Axial spondyloarthritis Non-radiographic axial spondyloarthritis (nr-axSpA) RINVOQ is indicated for the treatment of active non-radiographic axial spondyloarthritis in adult patients with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), who have responded inadequately to nonsteroidal anti- inflammatory drugs (NSAIDs). Ankylosing spondylitis (AS, radiographic axial spondyloarthritis) RINVOQ is indicated for the treatment of active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy. Atopic dermatitis RINVOQ is indicated for the treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents 12 years and older who are candidates for systemic therapy. Ulcerative colitis RINVOQ is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent. Crohn's disease RINVOQ is indicated for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent. Important Safety Information Contraindications RINVOQ 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. Special warnings and precautions for use RINVOQ should only be used if no suitable treatment alternatives are available in patients: -  65 years of age and older; -  patients with history of atherosclerotic cardiovascular (CV) disease or other CV risk factors (such as current or past long-time smokers); - patients with malignancy risk factors (e.g. current malignancy or history of malignancy) Use in patients 65 years of age and older Considering the increased risk of MACE, malignancies, serious infections, and all-cause mortality in patients ≥65 years of age, as observed in a large randomised study of tofacitinib (another JAK inhibitor), RINVOQ should only be used in these patients if no suitable treatment alternatives are available. In patients ≥65 years of age, there is an increased risk of adverse reactions with RINVOQ 30 mg once daily. Consequently, the recommended dose for long-term use in this patient population is 15 mg once daily. Immunosuppressive medicinal products Use in combination with other potent immunosuppressants is not recommended. Serious infections Serious and sometimes fatal infections have been reported in patients receiving RINVOQ. The most frequent serious infections reported included pneumonia and cellulitis. Cases of bacterial meningitis and sepsis have been reported with RINVOQ. Among opportunistic infections, TB, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis have been reported. RINVOQ should not be initiated in patients with an active, serious infection, including localized infections. RINVOQ should be interrupted if a patient develops a serious or opportunistic infection until the infection is controlled. A higher rate of serious infections was observed with RINVOQ 30 mg compared to 15 mg. As there is a higher incidence of infections in the elderly and patients with diabetes in general, caution should be used when treating these populations. In patients ≥65 years of age, RINVOQ should only be used if no suitable treatment alternatives are available. Tuberculosis Patients should be screened for TB before starting RINVOQ. RINVOQ should not be given to patients with active TB. Anti-TB therapy may be appropriate for select patients in consultation with a physician with expertise in the treatment of TB. Patients should be monitored for the development of signs and symptoms of TB. Viral reactivation Viral reactivation, including cases of herpes zoster, was reported in clinical studies. The risk of herpes zoster appears to be higher in Japanese patients treated with RINVOQ. Consider interruption of RINVOQ if the patient develops herpes zoster until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should occur before and during therapy. If hepatitis B virus DNA is detected, a liver specialist should be consulted. Vaccination 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 immunizations, including prophylactic zoster vaccinations, prior to initiating RINVOQ, in agreement with current immunization guidelines. Malignancy Lymphoma and other malignancies have been reported in patients receiving JAK inhibitors, including RINVOQ. In a large randomised active–controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥1 additional CV risk factor, a higher rate of malignancies, particularly lung cancer, lymphoma, and non-melanoma skin cancer (NMSC), was observed with tofacitinib compared to tumour necrosis factor (TNF) inhibitors. A higher rate of malignancies, including NMSC, was observed with RINVOQ 30 mg compared to 15 mg. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. In patients ≥65 years of age, patients who are current or past long-time smokers, or patients with other malignancy risk factors (e.g., current malignancy or history of malignancy), RINVOQ should only be used if no suitable treatment alternatives are available. Hematological abnormalities Treatment should not be initiated, or should be temporarily interrupted, in patients with hematological abnormalities observed during routine patient management. Gastrointestinal Perforations Events of diverticulitis and gastrointestinal perforations have been reported in clinical trials and from post–marketing sources. RINVOQ should be used with caution in patients who may be at risk for gastrointestinal perforation (e.g., patients with diverticular disease, a history of diverticulitis, or who are taking nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, or opioids. Patients with active Crohn's disease are at increased risk for developing intestinal perforation. Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis or gastrointestinal perforation. Major adverse cardiovascular events MACE were observed in clinical studies of RINVOQ. In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥1 additional CV risk factor, a higher rate of MACE, defined as CV death, non-fatal myocardial infarction and non-fatal stroke, was observed with tofacitinib compared to TNF inhibitors. Therefore, in patients ≥65 years of age, patients who are current or past long-time smokers, and patients with history of atherosclerotic CV disease or other CV risk factors, RINVOQ should only be used if no suitable treatment alternatives are available. Lipids RINVOQ treatment was associated with dose-dependent increases in lipid parameters, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hepatic transaminase elevations Treatment with RINVOQ was associated with an increased incidence of liver enzyme elevation. If alanine transaminase (ALT) or aspartate transaminase (AST) increases are observed and drug-induced liver injury is suspected, RINVOQ should be interrupted until this diagnosis is excluded. Venous thromboembolism Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) were observed in clinical trials for RINVOQ. In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in RA patients ≥50 years of age with ≥1 additional CV risk factor, a dose–dependent higher rate of VTE including DVT and PE was observed with tofacitinib compared to TNF inhibitors. In patients with CV or malignancy risk factors, RINVOQ should only be used if no suitable treatment alternatives are available. In patients with known VTE risk factors other than CV or malignancy risk factors (e.g. previous VTE, patients undergoing major surgery, immobilisation, use of combined hormonal contraceptives or hormone replacement therapy, and inherited coagulation disorder), RINVOQ should be used with caution. Patients should be re-evaluated periodically to assess for changes in VTE risk. Promptly evaluate patients with signs and symptoms of VTE and discontinue RINVOQ in patients with suspected VTE. Hypersensitivity reactions Serious hypersensitivity reactions such as anaphylaxis and angioedema have been reported in patients receiving RINVOQ. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy. Adverse reactions The most commonly reported adverse reactions in RA, PsA, and axSpA clinical trials (≥2% of patients in at least one of the indications) with RINVOQ 15 mg were upper respiratory tract infections, blood creatine phosphokinase (CPK) increased, ALT increased, bronchitis, nausea, neutropenia, cough, AST increased, and hypercholesterolemia. Overall, the safety profile observed in patients with psoriatic arthritis or active axial spondyloarthritis treated with RINVOQ 15 mg was consistent with the safety profile observed in patients with RA. The most commonly reported adverse reactions in AD trials (≥2% of patients) with RINVOQ 15 mg or 30 mg were upper respiratory tract infection, acne, herpes simplex, headache, blood CPK increased, cough, folliculitis, abdominal pain, nausea, neutropenia, pyrexia, and influenza. Dose dependent increased risks of infection and herpes zoster were observed with RINVOQ. The safety profile for RINVOQ 15 mg in adolescents was similar to that in adults. The safety and efficacy of the 30 mg dose in adolescents are still being investigated. The most commonly reported adverse reactions in the UC and CD trials (≥3% of patients) with RINVOQ 45 mg, 30 mg or 15 mg were upper respiratory tract infection, pyrexia, blood CPK increased, anemia, headache, acne, herpes zoster, neutropaenia, rash, pneumonia, hypercholesterolemia, bronchitis, aspartate transaminase increased, fatigue, folliculitis, alanine transaminase increased, herpes simplex, and influenza. The overall safety profile observed in patients with UC was generally consistent with that observed in patients with RA. Overall, the safety profile observed in patients with CD treated with RINVOQ was consistent with the known safety profile for RINVOQ. The most common serious adverse reactions were serious infections. The safety profile of upadacitinib with long–term treatment was generally similar to the safety profile during the placebo–controlled period across indications. This is not a complete summary of all safety information. See RINVOQ full Summary of Product Characteristics (SmPC) at www.ema.europa.eu Globally, prescribing information varies; refer to the individual country product label for complete information. About AbbVie in Rheumatology For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Anchored by a longstanding commitment to discovering and delivering transformative therapies, we pursue cutting-edge science that improves our understanding of promising new pathways and targets, ultimately helping more people living with rheumatic diseases reach their treatment goals. For more information, visit AbbVie in rheumatology . About AbbVie 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 our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com . Follow @abbvie on Twitter , Facebook , LinkedIn or Instagram . References SOURCE: AbbVie