Recent Publications - LA/ER Oral Therapy

Identification of a novel long-acting 4’-modified nucleoside reverse transcriptase inhibitor against HBV

Date: 
3/19/21
Citation: 

Higashi-Kuwata N, Hayashi S, Kumamoto H, Ogata-Aoki H, Das D, Venzon D, Hattori SI, Bulut H, Hashimoto M, Otagiri M, Takamune N, Kishimoto N, Davis D, Misumi S, Kakuni M, Tanaka Y, Mitsuya H. Identification of a novel long-acting 4'-modified nucleoside reverse transcriptase inhibitor against HBV. J Hepatol. 2020 Dec 14:S0168-8278(20)33843-5. doi: 10.1016/j.jhep.2020.12.006. Epub ahead of print. PMID: 33333207.

Although there are currently effective treatment options for HBV, treatment-resistant variants and the need for lifelong therapy pose a significant challenge. Therefore, the development of new treatment options is crucial to improve out-comes and quality of life. Herein, this study reports preclinical evidence showing that the anti-HBV agent, E-CFCP, has potent activity against wild-type and treatment-resistant variants. In addition, once-weekly oral dosing may be possible,which is preferable to the current daily dosing regimens.

Health Topics: 
LA/ER Oral Therapy
Viral Hepatitis

    Predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis across three phase 3 studies

    Date: 
    3/18/21
    Citation: 

    Cutrell AG, Schapiro JM, Perno CF, Kuritzkes DR, Quercia R, Patel P, Polli JW, Dorey D, Wang Y, Wu S, van Eygen V, Crauwels H, Ford SL, Baker M, Talarico CL, Clair MST, Jeffrey J, White CT, Vanveggel S, Vandermeulen K, Margolis DA, Aboud M, Spreen WR, van Lunzen J. Predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis across three phase 3 studies. AIDS. 2021 Mar 16. doi: 10.1097/QAD.0000000000002883. Epub ahead of print. PMID: 33730748.

    Efficacy and safety of long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV) dosed intramuscularly every 4 or 8 weeks has been demonstrated in three Phase 3 trials. Here, factors associated with virologic failure at Week 48 were evaluated post hoc.

    Health Topics: 
    HIV
    LA/ER Oral Therapy

      Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study

      Date: 
      12/9/20
      Citation: 

      Overton ET, Richmond G, Rizzardini G, Jaeger H, Orrell C, Nagimova F, Bredeek F, Deltoro MG, Swindells S, Andrade-Villanueva JF, Wong A, Khuong-Josses M, Solingen-Ristea RV, Eygen VV, Crauwels H, Ford S, Talarico C, Benn P, Wang Y, Hudson KJ, Chounta V, Cutrell A, Patel P, Shaefer M, Margolis DA, Smith KY, Vanveggel S, Spreen W. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study, The Lancet, 2020, ISSN 0140-6736.

      Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing. 

      Health Topics: 
      HIV
      LA/ER Oral Therapy

        Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection

        Date: 
        3/19/20
        Citation: 

        C. Orkin, K. Arasteh, M. Górgolas Hernández‑Mora, V. Pokrovsky, E.T. Overton, P.‑M. Girard, S. Oka, S. Walmsley, C. Bettacchi, C. Brinson, P. Philibert, J. Lombaard, M. St. Clair, H. Crauwels, S.L. Ford, P. Patel, V. Chounta, R. D’Amico, S. Vanveggel, D. Dorey, A. Cutrell, S. Griffith, D.A. Margolis, P.E. Williams, W. Parys, K.Y. Smith, and W.R. Spreen. Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection. N Engl J Med 2020;382:1124-35.DOI: 10.1056/NEJMoa1909512

        This study assessed whether switching to monthly injections of long-acting cabotegravir plus rilpivirine would be noninferior to continuing oral therapy in patients with HIV type 1 (HIV-1) who had viral suppression in response to oral induction therapy.

        Health Topics: 
        HIV
        LA/ER Injectable Therapy
        LA/ER Oral Therapy

          Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression

          Date: 
          3/4/20
          Citation: 

          Swindells, J.-F. Andrade-Villanueva, G.J. Richmond, G. Rizzardini, A. Baumgarten, M. Masiá, G. Latiff, V. Pokrovsky, F. Bredeek, G. Smith, P. Cahn, Y.-S. Kim, S.L. Ford, C.L. Talarico, P. Patel, V. Chounta, H. Crauwels, W. Parys, S. Vanveggel, J. Mrus, J. Huang, C.M. Harrington, K.J. Hudson, D.A. Margolis, K.Y. Smith, P.E. Williams, and W.R. Spreen. Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 SuppressionS. N Engl J Med 2020;382:1112-23.DOI: 10.1056/NEJMoa1904398

          Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence.

          Health Topics: 
          HIV
          LA/ER Injectable Therapy
          LA/ER Oral Therapy

            Considerations and challenges in developing novel long-acting antiretrovirals modalities for treatment and prevention of HIV-1 infection: a regulatory perspective

            Date: 
            9/3/19
            Citation: 

            Sampson MR, Troy SB, Belew Y, Arya V, Struble KA. Considerations and challenges in developing novel long-acting antiretrovirals modalities for treatment and prevention of HIV-1 infection: a regulatory perspective. Curr Opin HIV AIDS. 2019 Sep 3. doi: 10.1097/COH.0000000000000587. [Epub ahead of print]. PMID: 31483323.

            Outline some regulatory considerations and scientific challenges related to the development of long-acting antiretrovirals (ARVs) for the treatment and prevention of HIV-1 infection.

            Health Topics: 
            HIV
            LA/ER Implantable Therapy
            LA/ER Injectable Therapy
            LA/ER Oral Therapy
            LA/ER Transdermal Drug Delivery
            Pre-exposure Prophylaxis (PrEP)

              Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy

              Date: 
              1/9/18
              Citation: 

              Kirtane AR, Abouzid O, Minahan D, et al. Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy. Nat Commun. 2018;9(1):2. Published 2018 Jan 9. doi:10.1038/s41467-017-02294-6. PMID: 29317618; PMCID: PMC5760734.

              The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed.

              Health Topics: 
              HIV
              LA/ER Oral Therapy