Xeljanz XR (tofacitinib XR) / Pfizer - LARVOL DELTA

Synokem Pharmaceutical Gets CDSCO Panel Nod To Study Tofacitinib Extended Release Tablets (Medical Dialogues) - "Synokem Pharmaceutical has got approval from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) to conduct a Phase IV clinical trial of Tofacitinib Extended Release Tablets 11 mg...However, this approval is subject to the condition that the firm include serum NTpro BNP in the screening tool for participant recruitment to rule out 'significant cardiovascular disease'...After detailed deliberation, the committee recommended conducting a Phase IV Clinical Trial as per protocol presented by the firm with the following changes: 1) To include serum NT-pro BNP in the screening tool for participant recruitment to rule out 'significant cardiovascular disease'; 2) Serum lipid profile shall be performed on the last follow up visit....Accordingly, the expert panel suggested that the firm should submit the revised protocol to CDSCO."

New P4 trial • Cardiovascular

Brand prescription drugs to rise an average 4.5% in 2025 (SeekingAlpha) - "Pfizer...is increasing the price of more than 60 drugs, including its COVID-19 antiviral Paxlovid...and Xeljanz (tofacitinib) are going up in price between 3% and 5%....Merck (NYSE:MRK) is cutting the prices of two of its diabetes drugs, Januvia (sitagliptin) and Janumet (sitagliptin/metformin)."

Commercial • Ankylosing Spondylitis • Novel Coronavirus Disease • Psoriatic Arthritis • Rheumatoid Arthritis • Type 2 Diabetes Mellitus • Ulcerative Colitis

A Novel Oral 3D-Printed Delayed- and Extended-Release Tofacitinib (T19) for the Treatment of Rheumatoid Arthritis and Related Inflammatory Diseases (ACR Convergence 2024) - "The PK results demonstrate that T19 achieved the desired product design properties of delayed- and extended-release, as exhibited by the pharmacokinetic profiles and providing peak plasma concentrations in the early morning hours when morning symptoms are most present. The bioequivalence of exposure (AUC) and Cmax observed suggests a potential pharmacokinetic bridge to Xeljanz XRÒ, providing a basis for a 505(b)(2) application for the indications similar to the LD, XeljanzÒ and a potential therapeutic option for the patients with morning symptoms."

Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Pfizer Reports Strong Second-Quarter 2024 Results And Raises 2024 Guidance (Pfizer Press Release) - "The company’s updated guidance for revenue includes approximately $8.5 billion in anticipated revenues for Comirnaty and Paxlovid...Excluding contributions from Comirnaty and Paxlovid, revenues totaled $12.8 billion, an increase of $1.6 billion, or 14%, operationally compared with the prior-year quarter...Second-quarter 2024 Paxlovid revenues of $251 million increased $112 million, or 79%, operationally compared with the prior-year quarter, driven primarily by no second quarter 2023 U.S. sales in anticipation of transition to commercial markets in the second half of 2023, as well as increases in infections and demand in certain international markets in the second quarter of 2024...second-quarter 2024 operational revenue growth was driven primarily by...Vyndaqel family (Vyndaqel, Vyndamax, Vynmac) globally, up 71% operationally; Nurtec ODT/Vydura globally, up 44% operationally...partially offset primarily by lower revenues for: Xeljanz globally, down 34% operationally..."

Sales • Ankylosing Spondylitis • Infectious Disease • Inflammatory Bowel Disease • Migraine • Pain • Psoriasis • Rheumatoid Arthritis

A NOVEL ORAL 3D-PRINTED DELAYED- AND EXTENDED-RELEASE TOFACITINIB (T19) FOR THE TREATMENT OF RHEUMATOID ARTHRITIS AND RELATED INFLAMMATORY DISEASES (EULAR 2024) - "The PK results demonstrate that T19 achieved the desired product design properties of delayed- and extended-release, as exhibited by the pharmacokinetic profiles and providing peak plasma concentrations in the early morning hours when morning symptoms are most present. The bioequivalence of exposure (AUC) and C max observed suggests a potential pharmacokinetic bridge to Xeljanz XR ® , providing a basis for a 505(b)(2) application for the indications similar to the LD, Xeljanz ® and a potential therapeutic option for the patients with morning symptoms."

Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

EFFICACY AND SAFETY OF ADD-ON GENERIC TOFACITINIB EXTENDED RELEASE IN MODERATE TO SEVERE RHEUMATOID ARTHRITIS PATIENTS HAVING INADEQUATE RESPONSE TO DISEASE-MODIFYING ANTIRHEUMATOID DRUGS: REAL-WORLD STUDY FROM EASTERN PART OF INDIA (EULAR 2024) - "All patients subsequently were prescribed generic Tofacitinib XR 11 mg as add-on management along with Methotrexate, Leflunomide, Hydroxychloroquine and Sulfasalazine in 41.66%, 26.66%, 23.33% and 8.33% patients respectively. In this real-world analysis of adding generic Tofacitinib XR 11 mg to csDMARDs demonstrated effectiveness in achieving statistically significant functional improvement in patients having inadequate response to csDMARDs or biologic DMARDs. Safety profile was consistent with that reported from other reported studies."

Clinical • Real-world • Real-world evidence • Cardiovascular • Diabetes • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Herpes Zoster • Hypertension • Immunology • Infectious Disease • Inflammatory Arthritis • Metabolic Disorders • Obesity • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Tuberculosis • Varicella Zoster

Conventional vs Mechanistic IVIVC: A Comparative Study in Establishing Dissolution Safe Space for Extended Release Formulations. (PubMed, AAPS PharmSciTech) - "In the present study, we have performed comparative evaluation of mechanistic and conventional IVIVC for establishment of dissolution safe space using divalproex sodium and tofacitinib extended release formulations as case examples...The results suggest that a mechanistic approach of establishing IVIVC may be a flexible approach as it integrates physiological aspects. These findings suggest that mechanistic IVIVC has wider potential as compared to conventional IVIVC to gain wider dissolution safe space and thus can avoid potential clinical studies."

Clinical • Journal

XRPMS: Korean Post-marketing Surveillance for Xeljanz XR (clinicaltrials.gov) - P=N/A | N=200 | Recruiting | Sponsor: Pfizer | Trial completion date: Jun 2024 ➔ Dec 2026 | Trial primary completion date: Jun 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies

Evaluation of Tofacitinib in Prevention of Photosensitivity in Lupus (clinicaltrials.gov) - P1 | N=7 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed | N=10 ➔ 7

Enrollment change • Trial completion • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Preparation of Tofacitinib Sustained-Release Tablets Using Hot Melt Extrusion Technology. (PubMed, Pharm Dev Technol) - "Moreover, the extrudate size and compression force during tableting did not significantly affect drug release. In conclusion, the new tofacitinib sustained-release tablet prepared using hot melt extrusion showed a drug release behavior similar to that of Xeljanz XR®."

Journal

XRPMS: Korean Post-marketing Surveillance for Xeljanz XR (clinicaltrials.gov) - P=N/A | N=200 | Recruiting | Sponsor: Pfizer | Trial completion date: May 2025 ➔ Jun 2024 | Trial primary completion date: May 2025 ➔ Jun 2024

Trial completion date • Trial primary completion date • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies

Evaluation of Tofacitinib in Prevention of Photosensitivity in Lupus (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Mar 2024

Enrollment closed • Trial completion date • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

How to Position the Growing Number of Therapies in IBD (MedPageToday) - "At the American College of Gastroenterology (ACG) annual meeting opens in a new tab or window, Miguel Regueiro, MD...discussed the immunologic basis of novel biologic therapies for inflammatory bowel disease (IBD) during the GI Pathophysiology Course. In this video, Regueiro talks about how he utilizes different options for Crohn's disease and ulcerative colitis in his practice."

Video

Impact of Tofacitinib on Skeletal Muscle in RA (YouTube) - "Dr. Arthur Kavanaugh discusses abstract 0294 at the 2023 ACR Convergence meeting in San Diego, CA."

Video

The New “It Drug” for Ulcerative Colitis: Considerations for Use in High-Risk Patients (ACG 2023) - "Our patient was started on high dose extended release tofacitinib at 22mg qd along with high dose oral prednisone for management of UC. Although the first of its kind as an oral medication for the management of UC, the side effects and risks the medication poses are to be taken into careful consideration. Figure: A: Cecum B: Transverse Colon C: Descending Colon D: Descending Colon E: Rectum"

Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Pain • Rheumatoid Arthritis • Rheumatology • Ulcerative Colitis

Similar Results With Tofacitinib, Ustekinumab After Biologic Failure in Patients With UC (Gastroendonews) - "Stephen B. Hanauer...commented that a retrospective study with propensity matching 'provides evidence but not high-level evidence.' He said this study was 'more hypothesis-generating' than a reliable test of the relative clinical efficacy of tofacitinib and ustekinumab in UC patients with prior biologic failure....As newer agents enter the marketplace, 'we need more comparative studies, [but] these may or may or may not be forthcoming,' said Dr. Hanauer, providing the rationale for pursuing other methods to consider differences between available drugs."

Media quote

New treatment options for ulcerative colitis – are all orals the same? - "Valid until: 21 March 2024; In this CME course, Prof. Dr. medical Britta Siegmund and Dr. medical Stefan Schubert with the available treatment options for ulcerative colitis. Prof. Siegmund begins by presenting study data on the various Janus kinase inhibitors, tofacitinib, filgotinib and upadacitinib as well as the sphingosine-1-phosphate (S1P) receptor modulator ozanimod and drawing conclusions for practice."

Online CME

DDW 2023: In UC, Tofacitinib and Ustekinumab Perform Similarly After Biologic Failure (Gastroendonews) - "Stephen B. Hanauer...agreed that a retrospective study with propensity matching 'provides evidence but not high-level evidence.' He called this study in particular 'more hypothesis-generating' than a reliable test of the relative clinical efficacy of tofacitinib and ustekinumab in UC patients with prior biologic failure."

Media quote

Evaluation of Tofacitinib in Prevention of Photosensitivity in Lupus (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Apr 2023 ➔ Dec 2023 | Trial primary completion date: Apr 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Sun Pharma Gets CDSCO Panel Nod For Active Post Marketing Surveillance Of Tofacitinib ER Tablets (Medical Dialogues) - "Pharmaceutical major, Sun Pharma has got the green signal from the Subject Expert Panel (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) to conduct active post marketing surveillance (PMS) of Tofacitinib which is used for the treatment of adult patients with rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. This came after the firm presented its proposal for an active PMS study protocol titled 'A multi-centric, active post-marketing surveillance study to assess the safety and efficacy of Tofacitinib extended-release tablets 11mg for the treatment of adult patients with rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis' before the committee."

Clinical • Immunology • Psoriatic Arthritis • Rheumatoid Arthritis • Ulcerative Colitis

VEDOLIZUMAB, USTEKINUMAB AND TOFACITINIB AS TRIPLE THERAPY FOR ULCERATIVE COLITIS (CCCongress 2023) - "He had 2 infusions of infliximab 10 mg/kg continued post-discharge, and started mesalamine 4.8gm qd, 6-mercaptopurpine (6MP) 100mg qd, and prednisone taper...However, December 2020 colonoscopy showed severe (Mayo 3) recto-sigmoiditis with mild colitis in the descending to transverse colon, so tofacitinib XR 22 mg qd was added...Conclusion Combination therapies may be considered for suitable patients experiencing severe, refractory disease. Although patients with multiple comorbidities, frailty, immunosuppression or certain contraindications may not be well suited, this patient presents as an ideal candidate with no comorbidities and few other therapeutic options."

Gastroenterology • Gastrointestinal Disorder • Immune Modulation • Immunology • Infectious Disease • Inflammatory Bowel Disease • Ulcerative Colitis

Venous Thromboembolism Risk in Hospitalized Tofacitinib-Exposed Patients: A Real-World Experience of 533 Patients (AIBD 2022) - "Although non-significant, patients who received 5 mg QD and 11 mg extended release (XR) QD of tofacitinib had 5.93 times and 1.65 times risk of first VTE event, respectively, as compared to patients who utilized 10 mg BID or 22 mg XR tablets. We identified 533 patients meeting inclusion criteria of which 86 had a diagnosis of inflammatory bowel disease (IBD), 396 had RA, and 51 had ‘other’ (i.e., alopecia and psoriatic arthritis). Sixteen patients (3.0%) had a VTE event, of which one patient had a diagnosis of IBD, representing 1.2% of the total IBD patient population. The majority of VTE events (n=13; 81%) occurred during a hospital admission, while 3 (19%) were identified as 90-day post discharge events."

Clinical • Real-world evidence • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Ulcerative Colitis

EMA Crack Down on JAK Inhibitors (RheumNow) - "The European Medicines Agency's (EMA's) safety committee (PRAC) has issued a recommendation that the use of oral JAK inhibitors (tofacitinib, baricitinib, upadacitinib and filgotinib) be limited to certain at-risk patients unless no other suitable treatment alternatives are available. This advisory is not yet final or official has the EMA's Committee for Medicinal Products for Human Use (CHMP), needs to review and formally recommend a legally binding decision to the EMA."

Online posting

From TNF-Inhibitors to JAKs: Which Therapy for Which Patient? (HMP Global) - "During his session, 'Which Psoriasis Therapy for Which Patient,' presented at the 2022 Fall Clinical Dermatology Conference, Mark Lebwohl, MD, went over the many treatment options for patients with psoriasis and psoriatic arthritis, and the risks they could pose for these patients....'It looks like the IL-17s are going to be promising here. The problem is, we don't have enough registry data yet, so it's going to get question mark pluses. But I am pretty confident that these are going to be large green pluses as we have more data,' he stated. He also added that there are no data on the IL-23 blockers even though they reduce inflammation, but he hopes that will be a positive result."

Media quote • Psoriasis

Efficacy and Safety of JAK Inhibitors in Psoriatic Disease (RheumNow) - "There is a growing body of evidence demonstrating efficacy and safety of Janus kinase (JAK) inhibitors in patients with moderate-to-severe psoriasis (PSO) and psoriatic arthritis (PsA), according to a systematic review in BMC Rheumatology. Review of the literature identified 15 RCTs and 6757 PSO or PsA patients. The primary efficacy outcomes were a 75% improvement in the Psoriasis Area and Severity Index (PASI75) and a 20% improvement in the American College of Rheumatology composite score (ACR20)."

Online posting