Pediatric Praziquantel (PZQ) Formulation Program: Sitting next to each other led to partner with Astellas

An Interview with Jutta Reinhard-Rupp of Merck

Jutta Reinhard-Rupp, who leads the Global Health R&D organization at Merck, was interviewed by Nikkan Yakugyo in Tokyo during her business trip in Japan in the context of the recently announced Merck participation, as new funding partner, in the Global Health Innovative Technology (GHIT) Fund – a collaboration that will expand investments into research and development for neglected diseases worldwide.

She stated that "some years ago, sitting next to the person in charge of formulation development of Astellas Pharma Inc., Japan at an international conference by chance led to the joint development of the pediatric PZQ tablets for the treatment of schistosomiasis in pre-school aged children (<6 years old) living in African countries".

The pediatric PZQ formulation is being developed through an international, non-for-profit, public-private partnerships (Consortium) among six partners offering technical support and/or funds, including: the two pharmaceutical companies, Merck and Astellas Pharma Inc., a Swiss public institution, and a Brazilian pharmaceutical manufacturer. Aiming to initiate the supply at the end of 2019, the Consortium is currently conducting a Phase II (PII) clinical study in the Ivory Coast (West Africa).

Image: Reinhard-Rupp, Merck, explaining the difference in the tablet sizes:  current Cesol 600 mg and the new pediatric 150 mg tablets.

Schistosomiasis is caused by immune responses to schistosome larvae parasitic on fresh water snails as intermediary hosts, which enter from the skin, grow, and lay eggs in the human body. Left untreated, the disease can lead to anemia, stunted growth, reduced leaning ability and chronic inflammation of the organs which can be fatal in the most serious cases. African residents account for 90% of all infected people worldwide. There are 258 million patients on a global basis; about 10% are younger than 6 years.

More than 30 years have passed since PZQ tablets were launched; generics are also available today. However, there have been no clinical data regarding PZQ treatment of pediatric patients younger than 6 years; in addition, the current 600-mg tablets are large and bitter, making the treatment of young children extremely difficult.

Reinhard-Rupp, who had been considering measures to address the treatment gap for pediatric patients, looked back, and stated: "At an international conference held in The Netherlands at the end of 2011, I shared my thoughts with the responsible of the formulation development at Astellas Pharma Inc., who was sitting, by chance, next to me; he clearly showed a certain interest in the issue".

The idea of a partnership for a joint development, involving Merck and Astellas Pharma Inc., was soon after materialized, and the Pediatric PZQ Formulation program started in July 2012 under the Consortium of the several partners. Astellas Pharma Inc. offered their technologies for developing orodispersible formulations (not requiring water for administration), reducing the size of the tablet to a quarter (150 mg), and improving the taste (adding sweetness).

"Our encounter was an anecdote; as we say, life is about taking chances", Reinhard-Rupp observed, adding: "But our company usually applies and implements diverse strategies for development".

The GHIT Fund also favorably evaluates the development of the pediatric PZQ tablets, and it has been supporting both PI and II development phases of the program.

The GHIT Fund was originally a foundation financed by local pharmaceutical companies in Japan, but it has also begun to be supported by foreign-affiliated pharmaceutical companies as of June 2016. Regarding Merck's reasons for participating in the GHIT Fund, Reinhard-Rupp explained: "Beyond our collaboration with GHIT Fund in the context of the pediatric PZQ formulation program, Merck has always been interested in partnering with foundations, like the GHIT Fund, achieving successful global health outcomes. As the scope of participation has recently been extended to foreign-affiliated companies, we decided to become a funding partner of the GHIT Fund".

In line with this, she concluded: "Limited access to medical services is a challenge for developing countries facing poverty. We wish to address it together through this new collaboration".

Source:  Nikkan Yakugyo article (in Japanese) of July 4, 2016 / English Adaptation of the Article