Discontinued Products from the MATRIX Critical Path Portfolio

Early research and development is an inherently unpredictable process due to technical challenges, regulatory hurdles – even changes in the broader HIV prevention field can impact the viability of products. MATRIX was designed to approach early research and development in HIV prevention in a nimble and responsive way, employing a process for each of our products that is milestone- and benchmark-driven with clearly defined “Go/No Go” criteria to ensure that only the most promising products will advance to the first clinical trials of the product. A scientific advisory committee (SAG) plays an integral role in this process by providing independent unbiased assessment of each product’s progress in meeting its timelines and milestones within the five-year MATRIX award period. The SAG is an independent group of international experts in the fields of social behavioral research, drug development, clinical trials, pharmacology and regulatory affairs.

The MATRIX product developers are asked to submit progress reports every six months, and these are carefully reviewed by the SAG. The SAG makes recommendations to USAID regarding each product and then USAID makes the final decision. Following the February 2024 SAG, USAID has decided to discontinue further critical path product development of the Griffithsin fast-dissolving insert, which has been under development by the Population Council, and all four cabotegravir-based prevention products (injectable depot and dissolvable pellet implants with and without levonorgestrel), which have been under development by CONRAD. USAID’s decision was based on its assessment according to USAID’s stated strategic priorities that consider what the potential added value of the product may be and the likelihood for its successful implementation in low- and middle-income countries.

Why did this happen?  Both the Population Council and CONRAD have been working this past year to address technical challenges with their respective products, and it became clear that solving these issues would require more investment and time. Meanwhile, at the Conference for Retroviruses and Opportunistic Infections (CROI) earlier this month, ViiV reported that they have developed a 4-month cabotegravir injectable and are targeting a 6-month injectable. At the same time, Gilead’s Phase 3 trials evaluating a 6-month lenacapavir injectable is expected to be completed later this year (in women) and early next year (in men and transwomen). The HIV prevention landscape is changing and new ultra long-acting products, which could be “game-changers,” would have to have advantages over the 6-month injectables being developed by pharmaceutical companies. MATRIX hopes to support the development of 12-month ultralong-acting products through our Independent Special Project (ISP) funding mechanism. We are also actively seeking new products to add to the critical path product portfolio.

We understand that this news can make people wonder whether MATRIX, or any of our product developers, is struggling. The answer is no. These changes demonstrate that MATRIX is carrying out its mission of expediting the research and development of promising HIV prevention products for women by doing exactly what it was designed to do— to respond quickly and decisively to technical challenges and changes in the field and prioritizing those products that have the greatest chance for added value and success. There is nothing to hide, and hence, we intend to communicate these changes to our stakeholders and partners in the weeks and months ahead.

We would like to thank the teams at CONRAD and Population Council for their work on these MATRIX products. Their teams have worked with a great deal of professionalism and energy to bring these products to where they are today, helping to push the boundaries and advance the field. Their efforts should be recognized. Work under their MATRIX subawards will continue to bring ongoing studies to a close in the months ahead, so that although the products will depart MATRIX, the investigators can continue to seek funding and support with what they have learned during the products’ tenure within MATRIX. Women still need choices in HIV prevention, and we hope new pathways for the Griffithsin FDI and the dual prevention products with cabotegravir can be identified.

We thank the entire MATRIX family and our SAG for their input into these critical decisions, as well as USAID for their support of this research.