Expedited development and registration resulting in successful uptake of generic, pediatric dolutegravir products for low- and middle-income countries through an innovative public-private partnership

BACKGROUND: There are 1.7M children living with HIV (CLHIV) globally, with only 54% on treatment and 100,000 deaths each year. Poor viral suppression is observed in CLHIV due to lack of accessible, effective child-friendly formulations. A significant contributor is the time delay between adult and pediatric formulation development, followed by generic development via voluntary licensing mechanisms. Dolutegravir (DTG) was originally approved in 2013 by the US FDA for HIV treatment in adults and children ('¥12 years, '¥40kg). In 2018, WHO guidelines recommended DTG, in combination with NRTI backbone, as the preferred first-line treatment for adults and children. However, ViiV Healthcare''s child-friendly formulation ('¥4 weeks, '¥3kg), under development, was not yet available and generic development had not yet commenced.
DESCRIPTION: A public-private partnership, consisting of CHAI (funded by Unitaid), ViiV, Mylan and Macleods, was initiated to expedite the development and registration of generic, pediatric DTG dispersible tablets for use in low- and middle-income countries (LMICs) within ViiV''s pediatric licensing territory. CHAI/Unitaid provided a financial incentive for product development. ViiV provided a comprehensive technical package. CHAI and ViiV provided ongoing technical and regulatory support. A novel regulatory strategy enabled generic filing to the US FDA under the PEPFAR program during ViiV''s review period. FDA tentative approvals for pediatric DTG were obtained by Mylan and Macleods within 5 and 9 months of ViiV''s approval, respectively. The financial incentive enabled a global price agreement (75% price reduction from the existing standard of care).
LESSONS LEARNED: Technical support throughout the generic development process was critical to reducing timelines. Early engagement with the US FDA prior to generic filing was key to gain alignment on the proposed novel regulatory strategy and timing.
CONCLUSIONS: The collaborative partnership between CHAI, ViiV, Mylan and Macleods significantly accelerated development and registration of generic, pediatric DTG products. The gap between innovator and generic US FDA product approvals was reduced to months. The generic products launched at an affordable and sustainable price improving pediatric patient access in LMICs.

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