Forty-eight-Week Safety and Efficacy On-Treatment Analysis of Ibalizumab in Patients with Multi-Drug Resistant HIV-1

Abstract Background Management of multi-drug-resistant (MDR) HIV-1 remains a challenge. The advent of antiretroviral (ARVs) with novel mechanisms of action are needed to expand therapeutic options for MDR patients. Ibalizumab (IBA) is a humanized monoclonal antibody with a unique binding specificity to the CD4 domain 2, allowing it to block viral entry into host cells without CD4 depletion. Patients completing the 24-week Phase 3 study (TMB-301) continued treatment in study TMB-311. Here, we report the durable efficacy and long-term safety of IBA with an optimized background regimen (OBR) through 48 weeks of treatment. Methods TMB-301 was an open-label study investigating the antiviral activity and safety of IBA plus OBR in highly treatment-experienced patients with MDR HIV-1. Patients received an intravenous loading dose of 2,000mg followed by 800mg doses every 2 weeks for 24 weeks. 7 days after loading dose, an OBR was added with at least 1 additional sensitive agent throughout the study. Following completion of the 24-week TMB-301 study, patients continued to receive IBA at 800mg every 2 weeks under TMB-311 for up to 48 weeks. Safety and efficacy were assessed until 48 weeks. Results A total of 31 patients enrolled in TMB-301 completed the 24-week treatment period. Of 31 patients, 27 entered study TMB-311. These patients were highly resistant patients - 59% and 33% of patients had exhausted ≥3 and ≥4 ARV classes, respectively, and 7% of patients had HIV-1 resistant to all approved ARVs. IBA plus OBR was well tolerated. Of the 27 patients, 24 (89%) continued to receive treatment until Week 48. The three patients discontinued early due to non IBA-related reasons. No new or unexpected safety concerns emerged between Week 24 and 48. The potent suppression of viremia observed Week 24 was sustained through Week 48. Median viral load (VL) reduction from BL was 2.5 log10 at both Week 24 and 48. Of 27 patients (59%) 16 had VL <50 copies/ml and 17 (63%) patients had VL < 200 copies/ml. All 15 patients with VL < 50 copies/ml at Week 24 maintained viral suppression to Week 48. Conclusion IBA plus OBR continued to achieve high rates of virologic suppression through Week 48. The results support the durable efficacy and long-term safety of IBA in highly treatment-experienced MDR patients and offer a valuable treatment option for patients. Disclosures B. Emu, TaiMed Biologics: Employee and Shareholder, Salary; P. N. Kumar, TaiMed: Advisory Board and Investigator, Consulting fee and Grant recipient; G. Richmond, TaiMed: Investigator, Research support; S. Weinheimer, TaiMed: Employee, Salary; C. Marsolais, TaiMed: Commercial partner, Salary and Salary from Theratechnologies, commercial partner; S. Lewis, TaiMed: Employee, Salary and Salary from Theratechnologies, commercial partner

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Long-term safety and efficacy of rilpivirine in combination with nucleoside/nucleotide reverse transcriptase inhibitors in HIV-1 infected patients: 336-week rollover study of phase 2b and 3 clinical studies

Antiviral Therapy ◽

10.1177/13596535211062388 ◽

2021 ◽

pp. 135965352110623

Author(s):

Jean Michel Molina ◽

Luminita Ene ◽

Pedro Cahn ◽

Gerd Fätkenheuer ◽

Eric Van Wijngaerden ◽

...

Keyword(s):

Reverse Transcriptase ◽

Cell Count ◽

Virologic Failure ◽

Transcriptase Inhibitor ◽

Virologic Suppression ◽

Reverse Transcriptase Inhibitors ◽

Open Label ◽

Safety And Efficacy ◽

Hiv 1

Background To evaluate the long-term safety and efficacy of rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), in combination with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in human immunodeficiency virus (HIV)–infected patients. Methods RPV-treated HIV-infected patients from phase 2b or 3 studies rolled-over into this phase 3, open-label study and received RPV 25 mg once daily (QD) with choice of two NRTIs. Adverse events (AEs), plasma viral load, CD4+ cell count, and antiviral resistance were evaluated. Results Of the 482 patients treated, 437 (>90%) patients discontinued study treatment; 371 (77%) had switched to commercially available RPV, 14 (2.9%) discontinued due to AEs, and 6 (1.2%) had virologic failure. In this rollover study, patients were followed up to week 336, although data was limited beyond 288 weeks. Forty-five (9.3%) patients were still undergoing treatment at the time of data cut-off for the current analysis (8 February 2018). The most frequently reported AEs were pregnancy in 7 (1.5%) patients and syphilis in 5 (1.0%) patients. Grade 3–4 AEs were reported in 17 (3.5%) patients, and AEs possibly related to RPV in 23 (4.8%) patients. Over 288 weeks of treatment, 80.1% (95% CI: 74.9%; 84.3%) of patients maintained virologic suppression (HIV-1 RNA <50 copies/mL). The absolute CD4+ cell count increased over time until week 192 and remained constant thereafter. Conclusions RPV 25 mg QD in combination with an investigator-selected background regimen of two NRTIs demonstrated sustained long-term virologic suppression. The treatment was well-tolerated with no new safety findings.

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A Randomized, Open-Label Study of the Safety and Efficacy of Switching Stavudine or Zidovudine to Tenofovir Disoproxil Fumarate in HIV-1–infected Children With Virologic Suppression

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0000000000000289 ◽

2015 ◽

Vol 34 (4) ◽

pp. 376-382 ◽

Cited By ~ 11

Author(s):

Xavier Saez-Llorens ◽

Elizabeth Castaño ◽

Mobeen Rathore ◽

Joseph Church ◽

Jaime Deville ◽

...

Keyword(s):

Tenofovir Disoproxil Fumarate ◽

Virologic Suppression ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Safety And Efficacy ◽

Hiv 1

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POS0315 LONG-TERM SAFETY AND EFFICACY OF LENABASUM DURING 3 YEARS IN AN OPEN-LABEL EXTENSION (OLE) OF A PHASE 2 STUDY OF LENABASUM IN REFRACTORY SKIN DISEASE IN DERMATOMYOSITIS (DM)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2048 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 383.1-384

Author(s):

V Werth ◽

J. Concha ◽

J. Burroughs ◽

J. Okawa ◽

R. Feng ◽

...

Keyword(s):

Activity Score ◽

Phase 2 ◽

Open Label ◽

Safety And Efficacy ◽

Phase 2 Trial ◽

Phase 2 Study ◽

Patient Reported ◽

Open Label Extension ◽

To Receive

Background:Lenabasum is a synthetic, non-immunosuppressive, selective cannabinoid receptor type 2 agonist that activates resolution of inflammation. Lenabasum had acceptable safety and tolerability and improved efficacy outcomes in the initial 16-week double-blinded, randomized, placebo-controlled Part A of Phase 2 trial JBT101-DM-001 (NCT02466243) in DM subjects with refractory skin involvement. In that study, lenabasum or placebo was added to stable background treatment, with immunosuppressive therapies allowed.Objectives:To assess long-term safety and efficacy in DM subjects in this study.Methods:Subjects who completed Part A of the Phase 2 study (n = 22) were eligible to receive oral lenabasum 20 mg BID in an open-label extension (OLE) that assessed safety and efficacy at 4 weeks, then every 8 weeks.Results:20/22 (91%) eligible subjects enrolled in the OLE, following a mean interval of 31 weeks from the end of Part A, during which they continued to receive standard-of care treatments, to the start of the OLE during which lenabasum 20 mg BID was added. 17/20 (85%) subjects were on stable baseline immunosuppressive drugs. At the time of this data cut-off, 17 subjects were still enrolled, 17 had completed 140 months (2.7 years), and 15 had completed 156 months (3 years) of OLE dosing.All OLE subjects experienced at least 1 adverse event (AE), with 118 AEs during the OLE through Dec 2020. Most AEs were mild (n = 111, 94%), with 2 severe AEs (fatigue and metastatic prostate cancer) considered unrelated to lenabasum. AEs occurring in ≥ 3/20 OLE subjects were: URI (n = 5); fatigue (n = 4); nausea (n = 3); common cold (n = 3); UTI (n = 3); and DM flare (n = 3). No serious AEs related to lenabasum have been reported in this OLE to date. No subject discontinued the OLE because of an AE related to lenabasum.Improvement was seen in multiple physician- and patient-reported efficacy outcomes. CDASI activity score improved through the first 15 months of lenabasum treatment in the OLE and remained stable thereafter, with an improvement of ~20 points from the beginning of the study maintained from Month 15 through Year 3 in the OLE. CDASI damage score increased through the first year of the OLE, even though skin activity was decreasing, but lessened thereafter, returning after 3 years to about the same level it was at the beginning of the OLE. Other outcomes shown in Figure 1 followed the same general pattern as CDASI activity score, with improvement through the first 12-16 months of the OLE, then stability thereafter. Of note, 2 subjects had disease flares shortly after stopping lenabasum for conclusion of the OLE.Conclusion:Lenabasum continues to have a favorable safety and tolerability profile in the OLE of the Phase 2 trial JBT101-DM-001 with no serious AEs or study discontinuations related to lenabasum. The CDASI activity score and multiple other physician and patient-reported outcomes improved and have remained stable, showing durability of improvement in these patients with refractory skin disease. Skin damage was reversible and began to improve once skin activity stabilized. The limitations of attributing this improvement to lenabasum in the setting of open-label dosing is acknowledged. These data support further testing of lenabasum for the treatment of DM, and a Phase 3 study of lenabasum in DM is ongoing.Figure 1.Change from Baseline in Selected Efficacy Outcomes in OLE of Phase 2 Trial JBT101-DM-001Disclosure of Interests:Victoria Werth Grant/research support from: Investigator for Corbus Pharmaceuticals and received funding to conduct trials, Josef Concha: None declared, Julie Burroughs: None declared, Joyce Okawa: None declared, Rui Feng: None declared, Anisha Jobanputra: None declared, Robert Borucki: None declared, Kathleen Hally Employee of: Employee of Corbus Pharmaceuticals, Emily Hejazi: None declared, Michael Tillinger Employee of: Employee of Corbus Pharmaceuticals, Scott Constantine Employee of: Employee of Corbus Pharmaceuticals, Nancy Dgetluck Employee of: Employee of Corbus Pharmaceuticals, Barbara White Employee of: Employee and stockholder of Corbus Pharmaceuticals

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