PRO 140, a monoclonal antibody targeting CCR5, as a long-acting, single-agent maintenance therapy for HIV-1 infection

2018 ◽  
Vol 19 (3) ◽  
pp. 85-93 ◽  
Author(s):  
Kush Dhody ◽  
Nader Pourhassan ◽  
Kazem Kazempour ◽  
Derry Green ◽  
Shide Badri ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Maintenance Therapy ◽  
Single Agent ◽  
Antibody Targeting ◽  
Long Acting ◽  
Hiv 1

scholarly journals Efficacy, Safety, and Durability of Long-Acting Cabotegravir and Rilpivirine in Adults With HIV-1 Infection: ~5-Year Results From the LATTE-2 Study

2021 ◽  
Author(s):  
Graham H R Smith ◽  
W Keith Henry ◽  
Daniel Podzamczer ◽  
Maria Del Mar Masiá ◽  
Christopher J Bettacchi ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Comparable Efficacy ◽  
Maintenance Period ◽  
Injection Site Reactions ◽  
Long Acting ◽  
Hiv 1 ◽  
Extension Period

Abstract Background In the LATTE-2 phase IIb study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with HIV-1. Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over ~5 years. Methods After 20 weeks of oral cabotegravir + abacavir/lamivudine, participants were randomized to cabotegravir + rilpivirine LA Q8W or Q4W or continue oral ART through the 96-week maintenance period. In the extension period through Week 256, participants continued their current LA regimen (randomized Q8W/Q4W groups) or switched from oral ART to Q8W or Q4W LA therapy (extension-switch groups). Endpoints assessed included proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot algorithm) and adverse events (AEs). Results At Week 256, 186 (81%) of 230 participants in randomized Q8W/Q4W groups and 41 (93%) of 44 participants in extension-switch groups had HIV-1 RNA <50 copies/mL. No protocol-defined virologic failures occurred after Week 48. Injection-site reactions infrequently resulted in discontinuation (4 [2%] and 1 [2%] participants in randomized Q8W/Q4W and extension-switch groups, respectively). Three participants in randomized Q8W/Q4W groups experienced drug-related serious AEs, including 1 fatal serious AE (Q4W group); none occurred in extension-switch groups. Of 25 participants with AEs leading to withdrawal, 20 were in the randomized Q4W group; no AE leading to withdrawal occurred in >1 participant. Conclusions Cabotegravir + rilpivirine LA exhibited long-term efficacy and tolerability, demonstrating its durability as maintenance therapy for HIV-1 infection (ClinicalTrials.gov, NCT02120352).

Phase I/II study of MEDI-551, a humanized monoclonal antibody targeting CD19, in subjects with relapsed or refractory advanced B-cell malignancies.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8065-8065 ◽  
Author(s):  
Trishna Goswami ◽  
Andres Forero ◽  
Mehdi Hamadani ◽  
Anne Sonet ◽  
Gregor Verhoef ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Phase I ◽  
B Cell ◽  
Transmembrane Protein ◽  
Single Agent ◽  
Tumor Lysis Syndrome ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
B Cell Malignancies ◽  
Antibody Targeting

8065 Background: Novel B-cell targeting agents, including monoclonal antibodies such as rituximab, are among recent advances in treatment of B-cell malignancies. New approaches are needed for patients progressing after rituximab-based therapies. MEDI-551 is an afucosylated monoclonal antibody targeting CD-19, a B-cell restricted transmembrane protein with enhanced affinity and antibody-dependent cellular cytotoxicity. Methods: Pts with relapsed or refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia, or multiple myeloma received single agent MEDI-551 at dosages ranging from 0.5 mg/kg to 12 mg/kg via intravenous infusion over 28-day cycles; cohorts 1-6 received 0.5, 1, 2, 4, 8, and 12 mg/kg, respectively. Results: 25 pts were enrolled in the phase I portion Jun 2010–Aug 2011. No maximum tolerated dose (MTD) was achieved. Most AEs were grade 1/2 with dose-independent frequency and severity (Table). Six pts had grade 3 toxicities including tumor lysis syndrome, infusion reaction, thrombocytopenia, and neutropenia, or grade 4 neutropenia. No grade 5 AEs were seen. All pts recovered. Three partial responses (PR) and 2 complete responses (CR) were seen in DLBCL and FL pts at 0.5, 4, and 8 mg/kg. Activity included a CR lasting 9 mo. in a FL pt in cohort 1, who is currently being retreated with MEDI-551 on relapse. Conclusions: MEDI-551 demonstrated a safety profile warranting further study and showed no MTD reached at the highest dose studied. Anti-tumor activity is suggested by the responses achieved across dose levels. Phase II is currently enrolling subjects. This study is funded by MedImmune, LLC. [Table: see text]

Safety, Tolerability, and Pharmacokinetics of a Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC01LS in HIV-1-Exposed Newborn Infants

2021 ◽  
Author(s):  
Elizabeth J McFarland ◽  
Coleen K Cunningham ◽  
Petronella Muresan ◽  
Edmund V Capparelli ◽  
Charlotte Perlowski ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Half Life ◽  
Newborn Infants ◽  
Adjunct Treatment ◽  
Perinatal Hiv ◽  
Antiretroviral Prophylaxis ◽  
Terminal Half Life ◽  
Local Reactions ◽  
Long Acting ◽  
Hiv 1

Abstract Background Perinatal HIV-1 continues to occur due to barriers to effective antiretroviral prevention that might be mitigated by long-acting broadly neutralizing monoclonal antibodies (bNAbs). Methods Extended half-life bNAb, VRC01LS, was administered subcutaneously (SC) at 80 mg/dose after birth to HIV-1-exposed, non-breastfed (Cohort 1, n=10) and breastfed (Cohort 2, n=11) infants. Cohort 2 received a second dose (100mg) at 12 weeks. All received antiretroviral prophylaxis. VRC01LS levels were compared to VRC01 levels determined in a prior cohort. Results Local reactions (all Grade <2) occurred in 67% and 20% after Dose 1 and Dose 2, respectively. The weight-banded dose (mean 28.8 mg/kg) of VRC01LS administrated SC achieved a mean +SD plasma level of 222.3 + 71.6 mcg/mL by 24 hours and 44.0 + 11.6 mcg/mL at week 12, prior to Dose 2. The pre-established target of > 50 mcg/mL was attained in 95% and 32% at week 8 and 12, respectively. The terminal half-life was 37-41 days. VRC01LS level after one dose was significantly greater (p=<0.002) than after a VRC01 dose (20mg/kg). No infants acquired HIV-1. Conclusions VRC01LS was well tolerated with pharmacokinetics that support further studies of more potent long-acting bNAbs as adjunct treatment with ARVs to prevent infant HIV-1 transmission.

The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for Their Use as an Add-on Therapy in Schizophrenia

2020 ◽  
Vol 26 ◽  
Author(s):  
Felix-Martin Werner ◽  
Rafael Coveñas
Keyword(s):  
Clinical Trials ◽  
Maintenance Therapy ◽  
Antipsychotic Drug ◽  
Cognitive Functions ◽  
Antipsychotic Drugs ◽  
Psychotic Disorders ◽  
Therapeutic Effects ◽  
Treatment Resistant ◽  
Long Acting ◽  
Novel Antipsychotic

Background: Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders and, in this case, they can be treated with clozapine. In these patients and based on previous reviews on novel antipsychotic drugs, it is important to know whether an add-on therapy with new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. Objective: The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of current available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. Results: The mechanisms of action, the therapeutic effects and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole and lumateperone are up-dated. Published case reports of patients with treatmentresistant psychoses are also discussed. These patients were treated with clozapine but a high PANSS total score was observed. Only an add-on therapy with cariprazine improved the score and, above all, negative schizophrenic symptoms and cognitive functions. To ensure a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs may be a choice for a maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, are being investigated in preclinical and clinical trials. Conclusion: In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether a combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are a safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by an add-on therapy with cognition enhancing drugs.

Hair Growth in a Patient with Alopecia Areata on Tocilizumab

2021 ◽  
pp. 1-5
Author(s):  
Chloe J. Walker ◽  
Kelly E. Flanagan ◽  
James T. Pathoulas ◽  
Isabel Pupo Wiss ◽  
Maryanne M. Senna
Keyword(s):  
Monoclonal Antibody ◽  
Autoimmune Disease ◽  
Hair Loss ◽  
Alopecia Areata ◽  
Interleukin 6 ◽  
Hair Growth ◽  
Posterior Uveitis ◽  
Case Presentation ◽  
Antibody Targeting ◽  
Growth Changes

<b><i>Introduction:</i></b> Tocilizumab (TCZ), a recombinant humanized antihuman monoclonal antibody targeting interleukin-6 (IL-6) signaling, is often utilized in the management of autoimmune disease. Few reports have demonstrated hair growth changes in patients on TCZ. <b><i>Case Presentation:</i></b> Herein, we review the literature and report a 21-year-old woman with progressive alopecia areata (AA) presenting with AA improvement while on TCZ for concomitant posterior uveitis. <b><i>Discussion:</i></b> Our case demonstrates the potential ability of TCZ to disrupt IL-6 signaling involved in AA, leading to hair loss and regrowth.

scholarly journals Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3821
Author(s):  
Rita Meleddu ◽  
Angela Corona ◽  
Simona Distinto ◽  
Filippo Cottiglia ◽  
Serenella Deplano ◽  
...  
Keyword(s):  
Single Agent ◽  
Hiv Reverse Transcriptase ◽  
Substitution Pattern ◽  
Associated Functions ◽  
Dual Inhibition ◽  
Hiv Rt ◽  
Therapeutic Protocols ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Selection Of

Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. Pursuing on our investigation on potential anti HIV multi-target agents we have designed and synthesized a small library of biphenylhydrazo 4-arylthiazoles derivatives and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity. In particular, compound 2-{3-[(2-{4-[4-(hydroxynitroso)phenyl]-1,3-thiazol-2-yl} hydrazin-1-ylidene) methyl]-4-methoxyphenyl} benzamide bromide (EMAC2063) was the most potent towards RNaseH (IC50 = 4.5 mM)- and RDDP (IC50 = 8.0 mM) HIV RT-associated functions.

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