Xeljanz XR (tofacitinib XR) / Pfizer - LARVOL DELTA

NDA 203214/S-042, NDA 208246/S-028, NDA 213082/S-015 SUPPLEMENT APPROVAL (FDA) - "Please refer to your supplemental new drug applications (sNDAs) dated and received March 13, 2026 (NDA 203214/S-042, NDA 208246/S-028), and March 16, 2026 (NDA 213082/S-015), and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for Xeljanz (tofacitinib) tablets, extended-release (XR) tablets, and oral solution, respectively...These Prior Approval sNDAs provide for addition of a new subsection for the risk of progressive multifocal leukoencephalopathy (PML) to Warnings and Precautions Section 5.1, Serious Infections, and corresponding changes to Section 6 Adverse Reactions, Section 17 Patient Counseling Information, and the Medication Guide....We have completed our review of this application. It is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling."

FDA approval • Ankylosing Spondylitis • Immunology • Psoriatic Arthritis • Rheumatoid Arthritis • Ulcerative Colitis

Efficacy and Safety of Tofacitinib Versus Placebo in Patients With Early-Grade Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Trial. (PubMed, Int J Rheum Dis) - "Tofacitinib was not superior to placebo in early-grade knee osteoarthritis, and the large within-group improvement rebounded toward baseline by 6 months, consistent with a predominantly non-specific (contextual) response. Because participants were selected radiographically without inflammatory phenotyping, these findings do not support tofacitinib in unselected early-grade disease but cannot exclude benefit in an inflammatory phenotype; future trials should stratify accordingly, with longer follow-up and structural outcomes."

Clinical • Journal • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Safety and Efficacy of Tofacitinib for Chronic Granulomatous Disease With Inflammatory Complications (clinicaltrials.gov) - P1/2 | N=10 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Enrolling by invitation ➔ Completed | N=20 ➔ 10 | Trial completion date: Jan 2027 ➔ May 2026 | Trial primary completion date: Jan 2027 ➔ May 2026

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases

ChronIA001: Comparing the effectiveness of tofacitinib extended release (XR) chronotherapy, morning versus evening dosing, in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients from a patient's, clinical as well as a translational point of view. (clinicaltrialsregister.eu) - P4 | N=84 | Recruiting | Sponsor: Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC) | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies

Negotiations with participating drug companies will occur in 2026 and any negotiated and renegotiated prices will become effective January 1, 2028. (CMS Press Release) - "The selected drug list for the third cycle of negotiations is: Anoro Ellipta...Botox; Botox Cosmetic; Cimzia; Cosentyx; Entyvio...Orencia...Trulicity....Xeljanz; Xeljanz XR; Xolair."

Medicare • Allergy • Ankylosing Spondylitis • Asthma • Chronic Obstructive Pulmonary Disease • Crohn's disease • Idiopathic Arthritis • Immunology • Migraine • Psoriasis • Psoriatic Arthritis • Rheumatoid Arthritis • Ulcerative Colitis

Safety and Efficacy of Tofacitinib for Chronic Granulomatous Disease With Inflammatory Complications (clinicaltrials.gov) - P1/2 | N=20 | Enrolling by invitation | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial primary completion date • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases

Development of a controlled-release tofacitinib formulation using acid-sensitive pore-forming components for an osmotic drug delivery system. (PubMed, Eur J Pharm Sci) - "Times to maximum plasma concentration were 5 h for Xeljanz® XR 11 mg and 2 h for AID. Collectively, this modified approach reduces the initial lag time and allows for faster drug action."

Journal

Biocon Pharma Limited Receives U.S. FDA Approval for Tofacitinib Extended-Release Tablets (Biocon Press Release) - "Final approval received for 11mg strength and tentative approval for 22mg strength. Tofacitinib extended-release tablets are a Janus kinase (JAK) inhibitor indicated for Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis and Ulcerative Colitis."

ANDA • Ankylosing Spondylitis • Psoriatic Arthritis • Rheumatoid Arthritis • Ulcerative Colitis

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

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

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."

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