Manufacturing & Analytical Characterization
Stephanie Barrett, PhD
Director, Sterile & Specialty Products
Merck & Co., Inc.
Rahway, New Jersey
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Maria Cruanes, PhD Chemistry (she/her/hers)
Director Analytical Chemistry
Organon
Spring House, Pennsylvania
Despite significant medical advances, patient adherence remains a major hurdle to more broadly successful therapeutic regimens, independent of disease area. Efficacy, and the patient’s well-being, requires strict adherence to treatment regimens. Poor adherence can have serious adverse consequences to patient health and/or quality of life, as well as to the health care system as a whole. The lack of patient adherence can be attributed to a number of causes, including psychological factors, social stigma, high pill burden, challenges of managing multiple prescriptions, undesirable side effects, duration of therapy, or forgetting to take the medication. Alternatives to daily oral medications, including injectable long-acting formulations, have the potential to provide patients with more convenient therapeutic options. For example, long-acting implants such as Nexplanon® have offered women a convenient and robust method of contraception over conventional daily oral products.
Patient adherence is particularly important in the treatment of HIV infection. Highly durable regimens are required that mitigate the potential for the development of drug resistance that can render entire classes of drugs ineffective. Inadequate drug concentrations resulting from imperfect use of regimens that do not provide forgiveness for late or missed doses significantly increase the likelihood of the development of drug resistance. Long-acting injectable formulations of HIV antivirals could greatly improve adherence by increasing the duration between dosing, providing improved pharmacokinetics, and enabling health care providers the ability to track dosing status and compliance when administered in a clinical setting. Islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) with sub-nM potency is currently in clinical development for the treatment and prevention of HIV. The potency, pharmacokinetic, and physical properties of Islatravir make it an ideal candidate for extended duration dosing, including as a long-acting formulation. Implant formulations of Islatravir exhibited continuous, extended-duration drug release in rodents and rhesus with Islatravir plasma levels supportive of a dosing duration exceeding 6 months. The impact of long-acting parenteral formulations, preclinical and clinical studies on Islatravir implants will be discussed.