Focus Group 2 - Long-acting oral drugs and formulations: how do they stack up compared to other routes of drug delivery?
Oral Formulations vs Injectables, Patches and Implants
Current use indications for oral LA agents.
- Osteoporosis (Qday and Qweek); malaria; and TB prevention (Qweek).
- ISL and LEN are in development for HIV.
Possible demise of ISL as a LA oral agent for HIV treatment (once weekly in combination) and PrEP (once monthly).
- All studies are on hold as of 18 Nov 2021.
- The only AE is a selective reduction in TLC – mean 30% reduction in CD4 count and TLC was observed across treatment and prevention trials; the effect appears to be dose related.
- Many questions remain:
- Mechanism?
- Could the effect be mitigated by a different delivery method?
- Is there less concern with HIV prevention? CD4 counts are not typically monitored in HIV-neg people, and a drop may not be as serious as it is in a person with a low CD4 count to begin with.
- Can ISL be salvaged using different doses?
Overall enthusiasm for LA oral options compared to other routes of delivery.
- Familiarity/status quo – most feel comfortable with oral.
- Self-administration is a huge advantage. LAIs (CAB IM) need to be administered in a clinic setting. Greater burden on the client and stretching the health system.
- No extra high tech support needed (refrigeration, syringes, etc).
- No extra visits – in LMICs, systems are now using multi-month prescribing and 3 to 6 month visits. No extra health care workers and less HCW training.
Dr Tia Morton (DAIDS) – integration of behavioral social science research and development of LA agents.
- A portfolio of researchers are looking at discrete choice experiments where consumers weigh various pros and cons (e.g., oral vs injectable).
- Unveils interesting trade-offs and informs what attributes patients are willing to give up.
- Looking for ways to work with LEAP – pairing biomedical and biobehavioral researchers to address issues early in development to foster uptake and use.
How Long is Long Enough?
Need a range of options suitable for different preferences – choice is important, but logistics need to be simple.
- Any one approach does not have to be the solution for everyone, but if it works for a sizable proportion of population, then it should be pursued.
- The simpler the better for patients and facilities – need to be mindful of patient support issues during development (counseling, reminder process, linkage to care, peer HCWs).
- Dosing schedule needs to be equally simple to remember as daily (the status quo) – should be a regular interval that can be linked to other regular events (e.g., the first of the month or every week after Church, etc).
- There is not one solution – learn from the family planning space –there needs to be choice to allow for personal preference, especially for prevention.
General enthusiasm for once weekly or once monthly – anything more complicated was considered a disadvantage.
- Qweek vs Qday – some improved adherence data with weekly administration (higher adherence and longer persistence).
- Every other anything (week or month) becomes difficult to consistently remember and other logistical issues arise, such as insurance company coverage of refills (only allowed a certain # of refills per month).
- Qmonth may be the upper limit for oral formulations – there are pharmacological barriers to dosing intervals.
How to Monitor Adherence?
Most people would prefer traditional HIV support methods over newer digital strategies – there are scenarios where higher tech options may be preferred.
- Higher tech monitoring options.
- Digital pills with sensors that track whether a patient has taken the medication – first implemented in psychiatry (Abilify) without huge uptake.
- Digital monitoring platforms (digital adherence).
- Pediatric monitoring.
- Parents and caregivers might be more open to additional support when there are multiple caregivers, multiple households, or parents are juggling their own treatment with administering to their child.
- Digital tablets could help ensure that the child receives their medication.
- People taking PrEP may not consider themselves patients in need of monitoring.
Optimal Patient Populations for LA Orals?
- “Everyone” – anyone struggling with adherence, but certain populations are particularly vulnerable.
- Newborn prophylaxis, infants, children and adolescents.
- The postpartum period is characterized by many changes and transitions – women could link LA oral HIV agent to contraception (e.g., vaginal ring once-monthly).
- Patients already receiving directly observed therapy (e.g., methadone maintenance, syringe exchange etc) could link LA oral to this – DOT program is burdensome and would welcome less frequent dosing (i.e., TB).
- Any life circumstance with a sudden increase in burden or decreased access to care.
- Choice – ability to go back and forth between strategies.
Considerations for Development
How to roll out LA oral to pregnant women and children. A one-time “squirt” would be useful for neonatal prophylaxis.
- Breastfeeding infants (3TC/NVP).
- Mother fully suppressed (pregnant women)
Regulatory barriers unique to LA oral.
- There are no extra regulatory or manufacturing issues for tablets.
- Fewer concerns about price and supply issues with fewer meds to take or deliver.
- HIV treatment regimen needs to be one cadence – need to settle on one cadence for multiple active agents. Weekly ART could have potential for everyone, preferably in a combined tablet.
The issue is how people will engage with the health system.
Need to maintain regular conversations with generic manufacturers – LEAP can help with this.