Smart design of patient-centric long-acting products: from preclinical to marketed pipeline trends and opportunities

Bassand, C.; Villois, Alessia; Gianola, Lucas; Laue, Grit; Ramazani, Farshad; Riebesehl, Bernd; Sánchez-Félix, Manuel; Sedo, Kurt; Ullrich, Thomas; Romić, Marieta Duvnjak

doi:10.1080/17425247.2022.2106213

Cited by 18 publications

(10 citation statements)

References 73 publications

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“…The development of long-acting drug delivery systems is of immense importance in the field of healthcare, particularly in the context of chronic diseases where consistent medication adherence is critical for therapeutic efficacy. 6, 7, 9, 12, 28, 52, 53 The ISCD presented in this study represents a significant advancement in addressing critical challenges associated with existing drug delivery platforms.…”

Section: Discussionmentioning

confidence: 99%

An injectable in situ crosslinkable platform for ultra-long-acting delivery of hydrophilic therapeutics

Lee,

Zhao,

Chen

et al. 2023

Preprint

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Although hydrophilic drugs represent a large proportion of all therapeutics used to treat and manage chronic diseases, achieving their ultra-long-term delivery via an injectable system remains a major challenge. Implants have demonstrated potential for long-term delivery of both hydrophobic and hydrophilic drugs; however, they require invasive insertion process in a sterile setting, which restricts their suitability for resource-limited settings. Furthermore, implants tend to be more susceptible to local inflammation when compared to injectable alternatives. Here we report a solvent free, injectable, biodegradable, and in situ crosslinking depot (ISCD) platform for ultra-long term release of hydrophilic drugs. ISCD consists of a low molecular weight liquid pre-polymer methacrylated polycaprolactone (PCL). Both hydrophilic and hydrophobic drugs can be suspended/dissolved in the liquid polymer, and when injected along with a radical initiator and an accelerator, the polymer crosslinksin situ, resulting in a solid monolithic and degradable depot, integrating the unique advantages of injectability and retrievability. Low molecular weight PCL forms a dense mesh, which limits water influx/efflux and hence reduces the drug release. Liquid state of the polymer obviates the need for solvent, minimizing initial burst release due to the solvent exchange process, as observed within situforming implants. Drug release and ISCD degradation can be tailored by modifying their polymer network via altering the concentration of accelerator and initiator, molecular weight of methacrylated PCL, or by incorporation of a hydrophilic polymer or a non-crosslinking polymer. We demonstrated sustained release of seven hydrophilic drugs with varying solubility or drug combinations for over seven monthsin vitro. Ultra-long term drug release and depot degradation was also demonstrated in rats for at least six months without any evidence of local inflammation or fibrosis. Excitingly, the platform also enabled ultra-long term release of a model hydrophobic drug – tacrolimus for at least six months. To the best of our knowledge, this marks the first successful demonstration of an ultra-long term delivery of hydrophilic drugs using an injectable formulation. This platform holds promise for developing ultra-long acting therapies across a wide range of diseases.

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Section: Discussionmentioning

confidence: 99%

An injectable in situ crosslinkable platform for ultra-long-acting delivery of hydrophilic therapeutics

Lee,

Zhao,

Chen

et al. 2023

Preprint

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“…In a clinical trial comparing once-daily orally administered Rybelsus with once-weekly subcutaneously administered dulaglutide, a patient questionnaire indicated significantly higher quality of life with the oral Rybelsus in the total score, the “anxiety and dissatisfaction with treatment” domain, and the “satisfaction with treatment” domain . Sales of Rybelsus ($553 M in 2020), and its expected growth (575% by 2025), also indicate patient acceptance of the oral product, which was achieved by the DDS.…”

Section: Amount-controlled Ddsmentioning

confidence: 99%

Oral Drug Delivery Systems Applied to Launched Products: Value for the Patients and Industrial Considerations

Yoshida,

Kojima

2023

Mol. Pharmaceutics

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Drug delivery systems (DDS) control the amount, rate, and site of administration of drug substances in the body as well as their release and ADME (absorption, distribution, metabolism, excretion). Among the various types of DDS, amount-controlled DDS for solubilization and absorption increase the bioavailability. Time-and amount-controlled DDS are controlled release formulations classified as (1) membrane-type, (2) matrix-type, (3) osmotic-type, and (4) ion-exchange type. Timed-release formulations also control the time and amount of release and the absorption of drugs. Site-and amount-controlled DDS are characterized by colonic delivery and intestinal lymphtargeting to improve release and ADME of drug substances. Finally, site-, time-, and amount-controlled DDS are gastroretentive formulations and local delivery in the oral cavity to improve site retention, release, and ADME of drugs. DDS can enhance efficacy, reduce adverse effects, and optimize the dosing frequency of various drug products to increase patient value. This review focuses on patient value and industrial considerations of launched oral DDS. We provide a technological overview of candidate and marketed DDS, as well as the pros/cons of the technologies for industrialization with consideration to excipients, manufacturing, and storage stability. Moreover, to demonstrate the usefulness of the technology and support the selection and development of the best technologies for patients, we also describe patient value from clinical studies and analyses, particularly with regard to increased new medical options, higher efficacy, reduced adverse effects, reduced number of doses and clinic visits, easier administration, higher quality of life, greater adherence, and satisfaction.

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“…2,9,10 Less frequent dosing of ASOs, such as more than once in a month, could improve patient convenience and possibly result in higher patient adherence and more optimal therapeutic outcomes particularly when treating chronic diseases. 11 Long-acting injectable (LAI) formulations represent a means for achieving sustained drug release to enable less frequent dosing. 11−15 The most common LAI formulation strategies are biodegradable/biocompatible polymeric or oil-based formulations or crystalline drug suspensions.…”

Section: Introductionmentioning

confidence: 99%

“…, givosiran) or even less frequently ( e.g. , vutrisiran every third month or inclisiran every sixth month). ,, Less frequent dosing of ASOs, such as more than once in a month, could improve patient convenience and possibly result in higher patient adherence and more optimal therapeutic outcomes particularly when treating chronic diseases …”

Section: Introductionmentioning

confidence: 99%

“…Long-acting injectable (LAI) formulations represent a means for achieving sustained drug release to enable less frequent dosing. − The most common LAI formulation strategies are biodegradable/biocompatible polymeric or oil-based formulations or crystalline drug suspensions. However, these strategies suffer from either the inability to handle high drug load as would be required for monthly or less frequent dosing of ASOs where weekly/monthly doses are in the order of 100s of milligrams ,, or are suitable only for poorly soluble drugs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Injectable Biodegradable Silica Depot for Controlled Subcutaneous Delivery of Antisense Oligonucleotides with beyond Monthly Administration

McGowan,

Gennemark,

Akieh-Pirkanniemi

et al. 2023

Mol. Pharmaceutics

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Smart design of patient-centric long-acting products: from preclinical to marketed pipeline trends and opportunities

Cited by 18 publications

References 73 publications

An injectable in situ crosslinkable platform for ultra-long-acting delivery of hydrophilic therapeutics

An injectable in situ crosslinkable platform for ultra-long-acting delivery of hydrophilic therapeutics

Oral Drug Delivery Systems Applied to Launched Products: Value for the Patients and Industrial Considerations

Injectable Biodegradable Silica Depot for Controlled Subcutaneous Delivery of Antisense Oligonucleotides with beyond Monthly Administration

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