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Janssen Submits New Drug Application (NDA) To U.S. FDA For UPTRAVI ...
SOUTH SAN FRANCISCO, Calif., Sept. 30, 2020 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for UPTRAVI® (selexipag) as an injection for intravenous (IV) use for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults with WHO functional class (FC) II–III, who are currently prescribed oral UPTRAVI but are temporarily unable to take oral therapy. In patients with PAH, interruptions in treatment should be avoided due to the progressive nature of the disease.1
UPTRAVI is a selective, prostacyclin IP receptor agonist. Oral UPTRAVI was approved by the FDA in 2015 for the treatment of PAH to delay disease progression and reduce the risk of hospitalization.2
"Even relatively short-term PAH treatment interruptions due to a temporary inability to take oral medication, like during surgery, can have a significant negative impact on a person's health," said Neil Davie, Ph.D., Global Therapeutic Area Head, Pulmonary Hypertension, Janssen Research & Development, LLC. "We have demonstrated that continued treatment with UPTRAVI can significantly improve patients' long-term outcomes. Preventing an interruption of treatment with an IV formulation is an important therapeutic option and we are pleased to be one step closer to bringing this important treatment to the PAH community."
The NDA is based on the prospective, multi-center Phase 3 study designed to evaluate the safety and tolerability of patients with PAH temporarily switching from oral UPTRAVI to UPTRAVI IV, and then transitioning back to the initial oral dose. Results showed that UPTRAVI IV is suitable to maintain continuous dosing for short periods of time when oral administration of UPTRAVI is not feasible.1
About the UPTRAVI IV Study1
The UPTRAVI IV study (NCT03187678) was a prospective, multi-center, open-label single-sequence cross–over, Phase 3 study designed to assess the safety, tolerability and pharmacokinetics of temporarily switching between oral UPTRAVI and UPTRAVI IV. The study examined a stable dose of UPTRAVI tablets to a corresponding dose of UPTRAVI for injection and switching back to UPTRAVI tablets. The treatment and observation phase was divided into 3 periods. In Period 1, patients received their stable oral dose of UPTRAVI twice daily (morning and evening of Day 1). In Period 2, patients received three infusions of corresponding UPTRAVI IV doses (morning and evening of Day 2, and morning of Day 3). In Period 3, patients resumed their stable oral UPTRAVI dose twice daily in the evening of Day 3 for 9 days, which was continued through the safety follow-up. Patients were hospitalized during Periods 1 and 2.
All 20 enrolled patients completed the study as planned and received all UPTRAVI doses (oral or IV). The switch between oral UPTRAVI and UPTRAVI IV was well tolerated, and there were no unexpected safety findings. Adverse reactions that resulted from UPTRAVI for injection were similar to those associated with UPTRAVI tablets, with the exception of infusion site reaction. Prostacyclin-associated adverse events included headache, diarrhea, nausea, vomiting, pain in jaw, myalgia, pain in extremity, flushing and arthralgia.1
IMPORTANT SAFETY INFORMATION2
INDICATION
UPTRAVI® (selexipag) is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.
Effectiveness was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms.
Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), and PAH associated with congenital heart disease with repaired shunts (10%).
CONTRAINDICATIONS
Concomitant use of strong inhibitors of CYP2C8 (eg, gemfibrozil) with UPTRAVI is contraindicated.
WARNINGS AND PRECAUTIONS
Pulmonary Veno-Occlusive Disease (PVOD)
Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue UPTRAVI.
ADVERSE REACTIONS
Adverse reactions more frequent compared to placebo (≥3%) are headache (65% vs 32%), diarrhea (42% vs 18%), jaw pain (26% vs 6%), nausea (33% vs 18%), myalgia (16% vs 6%), vomiting (18% vs 9%), pain in extremity (17% vs 8%), flushing (12% vs 5%), arthralgia (11% vs 8%), anemia (8% vs 5%), decreased appetite (6% vs 3%), and rash (11% vs 8%).
These adverse reactions are more frequent during the dose titration phase.
Hyperthyroidism was observed in 1% (n=8) of patients on UPTRAVI and in none of the patients on placebo.
DRUG INTERACTIONS
CYP2C8 Inhibitors
Concomitant administration with gemfibrozil, a strong inhibitor of CYP2C8, doubled exposure to selexipag and increased exposure to the active metabolite by approximately 11-fold. Concomitant use of UPTRAVI with strong inhibitors of CYP2C8 is contraindicated.
Concomitant administration of UPTRAVI with clopidogrel, a moderate inhibitor of CYP2C8, had no relevant effect on the exposure to selexipag and increased the exposure to the active metabolite by approximately 2.7–fold. Reduce the dosing of UPTRAVI to once daily in patients on a moderate CYP2C8 inhibitor.
CYP2C8 Inducers
Concomitant administration with an inducer of CYP2C8 and UGT 1A3 and 2B7 enzymes (rifampin) halved exposure to the active metabolite. Increase UPTRAVI dose, up to twice, when co-administered with rifampin. Reduce UPTRAVI when rifampin is stopped.
DOSAGE AND ADMINISTRATION
Recommended Dosage
Recommended starting dose is 200 mcg twice daily. Tolerability may be improved when taken with food. Increase by 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to 1600 mcg twice daily. If dose is not tolerated, reduce to the previous tolerated dose.
Patients With Hepatic Impairment
For patients with moderate hepatic impairment (Child-Pugh class B), the starting dose is 200 mcg once daily. Increase by 200 mcg once daily at weekly intervals, as tolerated. Avoid use of UPTRAVI in patients with severe hepatic impairment (Child-Pugh class C).
Co-administration With Moderate CYP2C8 Inhibitors
When co-administered with moderate CYP2C8 inhibitors (eg, clopidogrel, deferasirox and teriflunomide), reduce the dosing of UPTRAVI to once daily. Revert back to twice daily dosing frequency of UPTRAVI when co-administration of moderate CYP2C8 inhibitor is stopped.
Dosage Strengths
UPTRAVI tablet strengths:
200, 400, 600, 800, 1000, 1200, 1400, and 1600 mcg.
Please see full Prescribing Information.
About Pulmonary Arterial Hypertension (PAH)
PAH is a specific form of PH that causes the walls of the pulmonary arteries (blood vessels leading from the right side of the heart to the lungs) to become thick and stiff, narrowing the space for blood to flow, and causing an increased blood pressure to develop within the lungs. PAH is a serious, progressive disease with a variety of etiologies and has a major impact on patients' functioning as well as their physical, psychological and social wellbeing. There is currently no cure for PH and it is often fatal.3,4,5 However, the last decade has seen significant advances in the understanding of the pathophysiology of PAH, transforming the prognosis for PAH patients from symptomatic improvements in exercise tolerance 10 years ago, to delayed disease progression today.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.
Learn more at www.Janssen.Com. Follow us at www.Twitter.Com/JanssenGlobal and www.Twitter.Com/JanssenUS. Janssen Research & Development, LLC is part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Cautions Concerning Forward-looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding UPTRAVI® (selexipag) and product development of UPTRAVI IV. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC or any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 29, 2019, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors", and in the company's most recently filed Quarterly Report on Form 10-Q, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.Sec.Gov, www.Jnj.Com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
Media contact:Natalia SalomaoMobile: +1 732-325-8306nsaloma7@its.Jnj.Com
Investor contact:Jen McIntyreOffice: +1 732-524-3922JMcInty3@its.Jnj.Com
References
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SOURCE Janssen Pharmaceutical Companies
UPTRAVI(R) (selexipag) Receives FDA Approval For Intravenous Use In ...
TITUSVILLE, N.J., July 30, 2021 /PRNewswire/ — The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has approved UPTRAVI(R) (selexipag) injection for intravenous (IV) use for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adult patients with WHO functional class (FC) II-III, who are temporarily unable to take oral therapy. UPTRAVI(R) IV is a therapeutic option that will allow patients to avoid short-term treatment interruptions and stay on UPTRAVI(R) therapy, as uninterrupted treatment is considered key for individuals with PAH. UPTRAVI(R) tablets were first approved by the FDA in 2015 to delay disease progression and reduce the risk of hospitalization for PAH.1
"Given the progressive nature of this disease, maintaining treatment is important to help control PAH. However, there are times where patients may be unable to take oral medications. For patients on UPTRAVI, bridging short-term temporary interruptions of UPTRAVI tablets with UPTRAVI IV may maintain the treatment effect and avoid the need to change therapy or re-titrate UPTRAVI tablets after re-initiation," said Kelly Chin, M.D.*, UPTRAVI(R) IV study senior author and Associate Professor of Internal Medicine and Director of the Pulmonary Hypertension Program at The University of Texas Southwestern Medical Center.
The FDA approval of the New Drug Application (NDA) for UPTRAVI(R) is based upon the findings from a prospective, multi-center, open-label single sequence cross-over Phase 3 study designed to assess the safety, tolerability and pharmacokinetics of temporarily switching between UPTRAVI(R) tablets and UPTRAVI(R) IV. The results of the study were published earlier this year in Respiratory Research and examined switching from a stable dose of UPTRAVI(R) tablets to a corresponding dose of UPTRAVI(R) IV and back to UPTRAVI(R) tablets.2
"Today marks an important day for patients who rely on UPTRAVI, as this new intravenous formulation meets a current unmet need for these patients. As part of our commitment to investing in research and understanding the science around the potential of UPTRAVI, we're inspired by this approval and are proud to be paving the way to advance treatment options and care for patients with PAH," said Neil Davie, PhD**, Global Therapeutic Area Head, Pulmonary Hypertension, Janssen.
The UPTRAVI(R) IV study enrolled 20 patients who received all UPTRAVI(R) doses (either tablets or IV). The study found that the switch between UPTRAVI(R) tablets and UPTRAVI(R) IV was well tolerated with no unexpected safety findings. Adverse events (AEs) that resulted from UPTRAVI(R) IV were similar to those associated with UPTRAVI(R) tablets, with the exception of infusion site reactions reported in two patients (both of which were considered mild-to-moderate in intensity and neither led to study and/or treatment discontinuation). The prostacyclin-associated AEs included headache, diarrhea, nausea, vomiting, pain in jaw, myalgia, pain in extremity, flushing, and arthralgia.2
*Kelly Chin, M.D., has received research support from Janssen and has served as a paid consultant to the company. She has not been compensated for any media work.
**Neil Davie is an employee of Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson & Johnson.
About UPTRAVI(R) (selexipag)
Selexipag, a selective prostacyclin IP receptor agonist, is a compound discovered by Nippon Shinyaku and licensed to Actelion Pharmaceuticals Ltd outside Japan. It is licensed for the oral treatment of PAH in more than 60 countries.
About the UPTRAVI(R) IV Study
The UPTRAVI(R) IV study (NCT03187678) was a prospective, multi-center, open-label single-sequence cross-over, Phase 3 study designed to assess the safety, tolerability and pharmacokinetics of temporarily switching between oral UPTRAVI(R) and UPTRAVI(R) IV in 20 patients. The study examined switching from a stable dose of UPTRAVI(R) tablets to a corresponding dose of UPTRAVI(R) IV and back to UPTRAVI(R) tablets. The treatment and observation phase was divided into three periods. In Period 1, patients received their stable oral dose of UPTRAVI(R) twice daily (morning and evening of Day 1). In Period 2, patients received three infusions of corresponding UPTRAVI(R) IV doses (morning and evening of Day 2, and morning of Day 3). In Period 3, patients resumed their stable oral UPTRAVI(R) dose twice daily in the evening of Day 3 for 9 days, which was continued through the safety follow-up. Patients were hospitalized during Periods 1 and 2.2
INDICATION AND IMPORTANT SAFETY INFORMATION
What is UPTRAVI(R)?
UPTRAVI(R) (selexipag) is a prescription medicine used to treat pulmonary arterial hypertension (PAH, WHO Group 1), which is high blood pressure in the arteries of your lungs.
UPTRAVI(R) can help delay (slow down) the progression of your disease and lower your risk of being hospitalized for PAH.
It is not known if UPTRAVI(R) is safe and effective in children.
IMPORTANT SAFETY INFORMATION
What are the possible side effects of UPTRAVI(R)?
The most common side effects are:
Talk to your doctor if you have a side effect that bothers you or does not go away. These are not all the possible side effects of UPTRAVI(R). For more information, ask your doctor or pharmacist.
You may report side effects to FDA at 1-800-FDA-1088 or www.Fda.Gov/medwatch.
Keep UPTRAVI(R) and all other medicines away from children.
What other medicines might interact with UPTRAVI(R)?
UPTRAVI(R) and other medicines may affect each other, causing side effects. Tell your doctor about all the medicines you are taking. Do not start any new medicine until you check with your doctor.
How should I take UPTRAVI(R)?
UPTRAVI(R)Tablets
UPTRAVI(R)given by intravenous (IV) injection
Please see full Prescribing Information and Patient Product Information.
About Pulmonary Arterial Hypertension (PAH)
PAH is a specific form of pulmonary hypertension (PH) that causes the walls of the pulmonary arteries (blood vessels leading from the right side of the heart to the lungs) to become thick and stiff, narrowing the space for blood to flow, and causing an increased blood pressure to develop within the lungs. PAH is a serious, progressive disease with a variety of etiologies and has a major impact on patients' functioning as well as their physical, psychological and social wellbeing. There is currently no cure for PAH and it is often fatal.3-5 However, the last decade has seen significant advances in the understanding of the pathophysiology of PAH, transforming the prognosis for PAH patients from symptomatic improvements in exercise tolerance 10 years ago, to delayed disease progression today.4,6
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.
Learn more at www.Janssen.Com. Follow us at www.Twitter.Com/JanssenGlobal and www.Twitter.Com/JanssenUS. Actelion Pharmaceuticals US, Inc. And Actelion Pharmaceuticals Ltd are Janssen Pharmaceutical Companies of Johnson & Johnson.
Cautions Concerning Forward-looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding UPTRAVI(R) (selexipag) and product development of UPTRAVI(R) IV. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC or any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 29, 2019, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors", and in the company's most recently filed Quarterly Report on Form 10-Q, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.Sec.Gov, www.Jnj.Com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
1.
UPTRAVI(R) (selexipag) full Prescribing Information. Actelion Pharmaceuticals US, Ltd.
2.
Klose H, Chin KM, et al. Respir Res 2021; 22, 34.
3.
Galie N, Humbert M, et al. Eur Heart J 2016; 37:67-119.
4.
Vachiery JL, Gaine S. Eur Respir Rev 2012; 21:313-20.
5.
Hoeper MG, Gibbs SR. Eur Respir Rev 2014; 23:450-7.
6.
Rosanio S, Pelliccia F et al. BioMed Research International 2014: 743868.
Media contact:
Natalia Salomao
Mobile: +1 732-325-8306
Nsaloma7@its.Jnj.Com
Investor contact:
Jen McIntyre
Office: +1 732-524-3922
JMcInty3@its.Jnj.Com
View original content to download multimedia:https://www.Prnewswire.Com/news-releases/uptravi-selexipag-receives-fda-approval-for-intravenous-use-in-adult-patients-with-pulmonary-arterial-hypertension-pah-301345104.Html
SOURCE Janssen Pharmaceutical Companies
Originally Published: July 30, 2021 at 6:30 AM EDT
Initiating Selexipag Within 12 Months Of PAH Diagnosis May ... - Healio
October 16, 2022
2 min read
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NASHVILLE, Tenn. — Initiation of oral selexipag within 12 months of pulmonary arterial hypertension diagnosis may reduce all-cause hospitalizations and overall medical costs, according to a new analysis.
"One of the key take-home findings is that earlier initiation of PAH combination therapy can deliver improvement in outcomes, particularly reduction in all-cause hospitalizations," Sumeet Panjabi, PhD, Senior Director, Real World Value & Evidence, Janssen Scientific Affairs, told Healio. "PAH patients exhibit high rates of hospitalizations including ICU admissions and, given almost 70% of patients remain on monotherapy, patients are often sub-optimally treated. There is a large opportunity for patients to be treated with more effective combination therapy, whether that is double or triple combination therapy, to improve outcomes and reduce the risk of hospitalization."
Source: Adobe Stock.
The aim of the current retrospective cohort study was to assess the impact of selexipag (Uptravi, Janssen) use within 12 months of diagnosis on rates of hospitalization and medical costs in real-world clinical practice.
The study included 1,083 adults with newly diagnosed PAH who received a PAH medication within 12 months following their diagnosis including 70 patients (66.3% women) who initiated selexipag and 1,013 patients (63% women) who did not initiate any prostacyclin pathway agent (PPA).
The most commonly used therapies in the selexipag group were combination therapies including oral selexipag plus a phosphodiesterase-5 inhibitor (40.6%) and oral selexipag plus an endothelin receptor antagonist (33.4%) or a combination of all three (17.2%). Most patients in the group that did not initiate any PPAs were treated with only one medication class (PDE5 inhibitor, 63.1%; endothelin receptor antagonist, 11.4%; soluble guanylate cyclase stimulator, 4.4%).
The rate of all-cause hospitalizations per 100 person-years was lower in the group that initiated selexipag within 12 months compared with the group that did not initiate PPA therapy (83 vs. 106; P = .039). However, the rate of PAH-related hospitalizations per 100 person-years was similar among the two groups (69 vs. 65), according to the results.
After adjusting for potential confounders, those who initiated selexipag within 12 months had a significantly lower rate (24%) of all-cause hospitalizations (incidence rate ratio = 0.76; 95% CI, 0.6-0.96), the researchers reported.
Annualized all-cause total per person per year (PPY) medical costs were significantly higher for patients who did not initiate any PPA within 12 months ($48,355 vs. $26,331; P = .0002). Those who did not initiate any PPA also had significantly higher hospitalization costs ($25,866 vs. $11,396; P = .0001) and physician visit utilization costs ($3,341 vs. $2,156; P = .004) compared with those who initiated selexipag within 12 months, according to the results.
PAH-related total costs ($22,121 vs. $13,763; P = .0241) and PAH-related hospitalization costs ($16,936 vs. $9,316; P = .0233) also were significantly higher in the non-PPA group. However, PAH-related ED visit costs were higher but not significantly so in the group that initiated early selexipag ($694 vs. $398), results showed.
"Our hypothesis going into the study was that we expected to see greater benefit in patients who initiated selexipag within 12 months. The findings really bore that out. I think that is a testament to the GRIPHON study, which studied selexipag and is one of the largest trials done in PAH. Being able to validate those findings in the real world reinforces how well the therapy works for patients in clinical practice," Panjabi told Healio.
Panjabi said a number of further studies are planned, looking at selexipag as part of a triple combination compared with double combination and outcomes of patients treated very selectively including with selexipag and macitentan (Opsumit, Janssen) together, for example.
This poster is being presented in the PAH Abstract Posters session Tuesday, Oct. 18, at CHEST 2022.
Reference: Sources/DisclosuresCollapse Source: Tsang Y, et al. Poster 2077. Presented at: CHEST Annual Meeting; Oct. 16-19, 2022; Nashville, Tennessee.Disclosures: The study was funded by Janssen. Panjabi reports being senior director of Real World Value & Evidence at Janssen and holding shareholder interest in Janssen. Please see the poster for all other authors' relevant financial disclosures.
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