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Findings from the extended LIBERTY studies and associated post-hoc analysis support the long-term efficacy and safety of ZYMFENTRA™, the first and only FDA-approved subcutaneous infliximab[1],...

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  • Findings from the extended LIBERTY studies and associated post-hoc analysis support the long-term efficacy and safety of ZYMFENTRA™, the first and only FDA-approved subcutaneous infliximab[1],[2]
  • Data from a post-hoc analysis of the LIBERTY-CD study showed that, despite affecting drug levels, anti-drug antibodies (ADAs) status appeared to have no significant impact on W54 clinical outcomes or discontinuation rates [3]

JERSEY CITY, N.J., May 21, 2024 /PRNewswire/ -- Celltrion USA announced today positive two-year results from the extended LIBERTY studies (LIBERTY-CD and LIBERTY-UC) for ZYMFENTRA™ (infliximab-dyyb) in adult patients with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC) after induction with intravenous (IV) infliximab, further supporting the efficacy and safety seen in previous pivotal studies. The data was shared during 18 oral and poster presentations at the Digestive Disease Week® (DDW) 2024 Annual Meeting in Washington, D.C., from May 18 to 21. 

The presentations included results of the two-year LIBERTY studies and a post-hoc analysis of the LIBERTY-CD study, which evaluated the impact of anti-drug antibodies (ADAs) on drug levels and efficacy in patients treated with ZYMFENTRA.

"Establishing the long-term efficacy and safety profile of ZYMFENTRA is an important step as we work to bring relief and remission to the millions of people worldwide living with Crohn's disease and ulcerative colitis," said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA. "These studies reaffirm efficacy and tolerance of ZYMFENTRA as maintenance therapy and underscore Celltrion USA's commitment to delivering different treatment options for patients in the gastroenterology space."

Two-year extension phase of LIBERTY studies

The extension phase of the LIBERTY studies (LIBERTY-CD and LIBERTY-UC) was carried out over a duration of 102 weeks (including 10 weeks of infliximab IV induction), expanding upon the initial LIBERTY trials. These two-year studies evaluated the long-term efficacy and safety of infliximab SC in patients diagnosed with Crohn's disease (CD) and ulcerative colitis (UC). In both LIBERTY-CD and UC studies, efficacy results, including but not limited to clinical remission, clinical response and corticosteroid-free remission, were generally well maintained at Week 102 compared to those of Week 54.

Post-hoc analysis of LIBERTY-CD study

A post-hoc analysis evaluated the impact of ADAs on clinical outcomes in patients with CD who received infliximab SC maintenance treatment. The analysis comprised 231 patients (ADA-positive: n=150; ADA-negative: n=81) who received infliximab SC as maintenance treatment. Notably, there were no statistically significant differences in clinical outcomes at Week 54 between ADA-positive and ADA-negative patients. Although mean trough serum infliximab concentrations at Week 54 were notably lower in the ADA-positive group than in the ADA-negative group (11.7 vs. 19.3 μg/mL; p<0.00001), both groups exceeded the historical therapeutic target concentration of 5 μg/mL, with comparable discontinuation rates observed between the groups.

"Results from the two-year extension phase LIBERTY studies, alongside post-hoc analysis, highlight important data supporting the efficacy and safety of ZYMFENTRA as a subcutaneous maintenance treatment option for people living with CD and UC," said Hetal Patel, Senior Director, Medical Affairs at Celltrion USA. "The post-hoc analysis reveals that ADAs showed no significant impact on clinical outcomes or discontinuation rates. These findings could be explained by the relatively high trough serum infliximab concentrations achieved by ADA-positive patients."[1],[2],[3]

PEREM long term study

In a large multi-center prospective cohort of inflammatory bowel diseases, the study assessed SC infliximab persistence, efficacy and tolerance after the switch from intravenous infliximab. The study enrolled 426 patients, with 72.4% diagnosed with Crohn's disease (CD). At baseline, 74% of participants were receiving the standard IV infliximab dose (5 mg/kg every 8 weeks), with 16% receiving combination therapy with an immunosuppressant. Drug persistence with SC infliximab was notably high at 95.3% among patients with complete data up to Week 48 (95% confidence interval: 93.2-97.5)[4] 

About Celltrion USA

Celltrion USA is Celltrion's U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to innovative biologics to improve care for U.S. patients. Celltrion currently has five biosimilars approved by the U.S. FDA: INFLECTRA® (infliximab-dyyb), TRUXIMA® (rituximab-abbs), HERZUMA® (trastuzumab-pkrb), VEGZELMA® (bevacizumab-adcd) and YUFLYMA®(adalimumab-aaty) as well as a new biologic ZYMFENTRA™. Celltrion USA will continue to leverage Celltrion's unique heritage in biotechnology, supply chain excellence and best-in-class sales capabilities to improve access to high-quality biopharmaceuticals for U.S. patients. For more information, please visit: www.celltrionusa.com.

About Digestive Disease Week®

Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting from May 18-21, 2024. The meeting showcases more than 4,400 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at www.ddw.org

About ZYMFENTRA™ (infliximab-dyyb)

ZYMFENTRA is a prescription medicine used as an injection under the skin (subcutaneous injection) by adults for the maintenance treatment of: Moderately to severely active ulcerative colitis following treatment with an infliximab product given by intravenous infusion (IV) and moderately to severely active Crohn's disease following treatment with an infliximab product given by intravenous infusion (IV). ZYMFENTRA blocks the action of tumor necrosis factor-alpha (TNF-alpha), a protein that can be overproduced in response to certain diseases and cause the immune system to attack normal, healthy parts of the body.

ZYMFENTRA (infliximab-dyyb) was approved by the FDA through the Biologics License Application (BLA) under the 351 (a) pathway of the Public Health Service Act (a "stand-alone" BLA). ZYMFENTRA is a self-injected form of infliximab and thus will be under patent protection for its dosage form by 2037 and for its route of administration by 2040.

ZYMFENTRA (infliximab-dyyb) U.S. Use and Important Safety Information

ZYMFENTRA is a prescription medicine indicated in adults for maintenance treatment of:

  • Moderately to severely active Crohn's disease following treatment with an infliximab product administered intravenously.
  • Moderately to severely active ulcerative colitis following treatment with an infliximab product administered intravenously.

It is not known if ZYMFENTRA is safe and effective in children under 18 years of age.

What is the most important information I should know about ZYMFENTRA?

SERIOUS INFECTIONS

Patients treated with ZYMFENTRA are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Discontinue ZYMFENTRA if a patient develops a serious infection or sepsis.

Reported infections include:

  • Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with ZYMFENTRA. Treatment for latent infection should be initiated prior to treatment with ZYMFENTRA.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with ZYMFENTRA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with ZYMFENTRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Risk of infection may be higher in patients greater than 65 years of age, patients with comorbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with infliximab included arthritis bacterial, pneumonia, and urinary tract infection.

MALIGNANCIES

Malignancies, some fatal, have been reported in children, adolescents, and young adults treated with TNF blockers, including infliximab products.

Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

Post-marketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis, and most were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. Carefully assess the risks and benefits of treatment with ZYMFENTRA, especially in these patient types.

In clinical trials of all TNF blockers, more cases of malignancies were observed compared with controls and the expected rate in the general population. In clinical trials of some TNF blockers, including infliximab products, more cases of other malignancies were observed compared with controls. As the potential role of TNF blocker therapy in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy.

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

CONTRAINDICATIONS

ZYMFENTRA is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab-dyyb, other infliximab products, any of the inactive ingredients of ZYMFENTRA or any murine proteins (severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness).

HEPATITIS B VIRUS REACTIVATION

TNF blockers, including infliximab products, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating ZYMFENTRA. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing ZYMFENTRA for patients identified as carriers of HBV, and monitor closely for active HBV infection during and following termination of therapy with ZYMFENTRA. Discontinue ZYMFENTRA in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of ZYMFENTRA, and monitor patients closely.

HEPATOTOXICITY

Hepatobiliary disorders, including acute liver failure, jaundice abnormal hepatic function, hepatic steatosis, hepatitis, hepatotoxicity, hyperbilirubinemia, and non-alcoholic fatty liver, have been reported in patients receiving infliximab products post-marketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the upper limit of normal) develop, ZYMFENTRA should be discontinued, and a thorough investigation of the abnormality should be undertaken.

CONGESTIVE HEART FAILURE

Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Some cases had a fatal outcome. In several exploratory trials of other TNF blockers in the treatment of CHF, there were greater proportions of TNF-blocker-treated patients who had CHF exacerbations requiring hospitalization or increased mortality. ZYMFENTRA has not been studied in patients with a history of CHF and ZYMFENTRA should be used with caution in patients with CHF.

HEMATOLOGIC REACTION

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to infliximab-product therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of ZYMFENTRA in patients who develop significant hematologic abnormalities.

HYPERSENSITIVITY AND OTHER ADMINISTRATION REACTIONS

In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylaxis, hypotension, and serum sickness) have been reported following administration of infliximab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA.

INJECTION SITE REACTIONS

In clinical studies, localized injection-site reactions were reported following administration of ZYMFENTRA. If a clinically significant injection-site reaction occurs, institute appropriate therapy and discontinue ZYMFENTRA.

NEUROLOGIC REACTIONS

Agents that inhibit TNF have been associated with central nervous system (CNS) manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering ZYMFENTRA in patients with these disorders and consider discontinuation if these disorders develop.

RISK OF INFECTION WITH CONCURRENT ADMINISTRATION OF OTHER BIOLOGICS PRODUCTS

Serious infections and neutropenia have been reported with concurrent use of ZYMFENTRA with other immunosuppressive biological products. The concurrent use of ZYMFENTRA with other immunosuppressive biological products used to treat UC and CD may increase the risk of infection and is not recommended.

RISK OF ADDITIVE IMMUNOSUPPRESSIVE EFFECTS FROM PRIOR BIOLOGICAL PRODUCTS

Consider the half-life and mode of action of prior biological products to avoid unintended additive immunosuppressive effects when initiating ZYMFENTRA.

AUTOIMMUNITY

Treatment with TNF blockers may result in the formation of autoantibodies and in the development of a lupus-like syndrome. Discontinue ZYMFENTRA treatment if symptoms of a lupus-like syndrome develop.

VACCINATIONS AND USE OF LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS

Prior to initiating ZYMFENTRA, update vaccinations in accordance with current vaccination guidelines. Live vaccines or therapeutic infectious agents should not be given with ZYMFENTRA due to the possibility of clinical infections, including disseminated infections. At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to ZYMFENTRA.

ADVERSE REACTIONS

In clinical trials with ZYMFENTRA, the most common adverse reactions occurring in ≥3% of ZYMFENTRA -treated patients included site reactions, COVID-19, anemia, arthralgia, infection site reaction, increased alanine aminotransferase and abdominal pain for UC, and COVID-19, headache, upper respiratory tract infection, injection site reaction, diarrhea, increased blood creatine phosphokinase, arthralgia, increased alanine aminotransferase, hypertension, urinary tract infection, neutropenia, dizziness and leukopenia for CD.

Please click for Full U.S. Prescribing Information.

Globally, prescribing information varies; refer to the individual country product label for complete information.

References

[1] Jean F. Colombel et al., Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn's disease: 2 years results of the LIBERTY-CD study. Poster (Su1762). Presented at DDW 2024.

[2] Bruce E. Sands et al., Subcutaneous infliximab (CT-P13 SC) for ulcerative colitis: 2-year extension results of the LIBERTY-UC study. Poster (Su1779). Presented at DDW 2024.

[3] Jean F. Colombel et al., Impact of immunogenicity on clinical outcomes in patients with Crohn's disease receiving maintenance treatment with subcutaneous infliximab: A post hoc analysis of the LIBERTY-CD study. Poster (Su1765). Presented at DDW 2024.

[4] Nicolas Mathieu et al., Persistence, efficacy and tolerance of subcutaneous infliximab after switch from intravenous infliximab in IBD patients in remission: one-year results from a multicenter prospective cohort. Oral Presentation (1179). Presented at DDW 2024.

Contacts
Sarah Amundsen
samundsen@apcoworldwide.com
+1 920-946-0918

Cision | Tue, May 21 2024 02:01 PM AEST

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Investing.com-- Oil prices edged lower in Asian trade on Tuesday, as markets were uncertain how the Iran President’s death could affect supplies, while traders feared that high U.S. interest rates w

Investing | Tue, May 21 2024 12:34 PM AEST

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Investing.com-- Oil prices edged lower in Asian trade on Tuesday, as markets were uncertain how the Iran President’s death could affect supplies, while traders feared that high U.S. interest rates will eat into demand this year.

Iranian President Ebrahim Raisi, who was seen as a successor to Supreme Leader Ayatollah Ali Khamenei, was killed in a helicopter crash over the weekend. But traders were uncertain just what bearing his death would have on the oil-producing nation, especially as the potential for a war with Israel diminished.

Brent oil futures expiring in July fell 0.4% to $83.38 a barrel, while West Texas Intermediate crude futures fell 0.4% $78.95 a barrel by 22:22 ET (02:22 GMT).

Concerns over the Saudi King’s health also presented some uncertainty for markets.

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High rates are expected to potentially chip away at demand, while also limiting money for investment and economic growth, which usually support oil demand.

The minutes of the Fed’s late-April meeting are due on Wednesday and are expected to provide more cues on the rate outlook. More Fed officials- specifically members of the rate-setting committee- are also set to speak in the coming days.

The International Energy Agency had last week trimmed its outlook for crude demand this year, citing concerns over weaker economic conditions due to pressure from interest rates.

But the Organization of Petroleum Exporting Countries (OPEC) had maintained its demand forecast, citing strength in top exporter China.

China has been a point of confidence for oil demand, especially as Beijing rolled out a string of stimulus measures in recent weeks to support growth.

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This article first appeared in Investing.com

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Investing.com-- Oil prices slipped lower Monday, handing back early gains after the confirmation of the death of Iran’s President in a helicopter crash.

Investing | Mon, May 20 2024 10:32 PM AEST

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Investing.com-- Oil prices slipped lower Monday, handing back early gains after the confirmation of the death of Iran’s President in a helicopter crash.

At 08:30 ET (12:30 GMT), Brent oil futures fell 0.5% to $83.53 a barrel, while West Texas Intermediate crude futures dropped 0.6% to $79.10 a barrel.

Iran stability in focus after helicopter crash

Crude prices rose early Monday following reports that a helicopter carrying Iranian President Ebrahim Raisi and his foreign minister crashed in mountainous terrain due to bad weather conditions over the weekend.

Raisi was seen as a contender to become Iran’s next supreme leader - the highest political position in the oil-producing nation.

His death was later confirmed by state media, but tensions have eased with the Iranians not accusing any outside bodies of foul play.

Additionally, the county's oil policy should not be affected given current Supreme Leader Ayatollah Ali Khamenei holds ultimate power with a final say on all state matters.

Fears that continued instability in the Middle East could disrupt oil supplies from the region have been a key point of support for oil prices, keeping Brent trading comfortably above $80 for most of 2024.

Fears that continued instability in the Middle East could disrupt oil supplies from the region have been a key point of support for oil prices.

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That said, there remains a great deal of caution with the oil markets ahead of a slew of upcoming cues on U.S. interest rates and the economy this week.

The minutes of the Federal Reserve’s late-April meeting are due this week, as are speeches from a string of Fed officials.

Markets were also on edge before a meeting of the Organization of Petroleum Exporting Countries and allies (OPEC+), which is scheduled for June 1. Any updates on the cartel’s plans to maintain ongoing production cuts will be squarely in focus.

"We might have to wait for further clarity from OPEC+ and its output policy for the second half of the year to provide any impetus to the market and for it to break out of its recent range," said analysts at ING, in a note.

(Ambar Warrick contributed to this article.)

This article first appeared in Investing.com

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