Pharma Task Force (IDDI Global Alliance): Workstreams 2021-23

• Create and facilitate a platform to allow discussion and harmonisation of ideas between Pharma, Academia and Regulators to build awareness on the disease and explore options to early diagnosis and treatment.
• Explore innovative and suitable clinical trial designs, endpoints, biomarkers and re-purposing drugs opportunities for different forms of pulmonary hypertension (PH).
• Leverage deep phenotyping programmes at PH specialised centres to inform and enrich new clinical trial designs based on patient subsets (“Personalised Medicine”).
• Explore acceleration potential of clinical trials to bring novel or repurposed drugs as soon as possible to this critically ill group of pulmonary hypertension patients.
• Include the view of patients, regulators and nurses, and their advocacy groups.

• To be recognised as a centre of excellence for free, in-depth scientific exchange of information and its timely utilisation in the field of pulmonary vascular diseases.
• Drive the finding of innovative treatments, and potentially a cure for pulmonary hypertension and other PH related rare diseases.
• Successfully harmonise and develop protocol designs, biomarkers and endpoints to expedite availability of critical new treatments and drugs especially those for treating rare diseases.
• Provide scientific input to guidelines for the optimal diagnosis and treatment of all forms of pulmonary hypertension globally including those relevant to low, middle and high income countries .

The Innovative Drug Development Initiative (IDDI) was established in 2017 under the leadership of Paul Corris (PVRI Chair of the Board), Sylvia Nikkho (Bayer), Peter Fernandes ( Bellerophon Therapeutics). The IDDI is a unique core activity within the PVRI facilitating the development of novel treatments for patients with pulmonary vascular diseases (PVD) and establish them into clinical practice.

IDDI provides a platform for academia, the pharmaceutical industry, patient representatives and drug regulators to openly discuss questions surrounding the future of trials comprising novel drugs. Importantly, the four workstreams: clinical trial design; endpoints; biomarkers; and repurposed drugs were interlinked and mutually supportive, chaired by an expert from academia and one from pharmaceutical industry.

In 2020 the IDDI has completed its major goal to establish a series of guidance documents in Pulmonary Circulation:

• Clinical trial design in phase 2 and 3 trials for pulmonary hypertension. Pulmonary Circulation. October 2020. by Nikkho S, Fernandes P, White RJ, Deng C (CQ), Farber HW, Corris PA.
• Novel composite clinical endpoints and risk scores used in clinical trials in pulmonary arterial hypertension. Pulmonary Circulation. October 2020. by Sitbon O, Nikkho S, Benza R, et al.
• Role of biomarkers in evaluation, treatment and clinical studies of pulmonary arterial hypertension. Pulmonary Circulation. October 2020. by Hemnes A, Rothman AMK, Swift AJ, Zisman LS.
• Repurposing of medications for pulmonary arterial hypertension. Pulmonary Circulation. 2020 by Toshner M, Spiekerkoetter E, Bogaard H, Hansmann G, Nikkho S, Prins KW.

As noted in editorial, this collection of leading experts in the field reflects on previous experience, review present understanding, and consider how their respective areas of expertise may develop in years ahead.

There is more to come, PVD matters to patients. It is still a field of high unmet medical need. Although great progress has been made in Pulmonary Arterial Hypertension and Chronic Thromboembolic pulmonary hypertension with several treatment options available, there is still no cure for those indications and no disease specific treatment for other forms of PH. Studies are getting more and more complex with endpoints not seen as meaningful (6-minute walking distance) or feasible (time to clinical worsening) anymore. Ideas on novel clinical trial design and endpoints require regulatory acceptance based on evaluation of existing registry or clinical data bases using artificial intelligence. Further, PVD is not only a disease of developed countries, it needs to be recognised as a global burden of disease and access to medicine to be ensured.

Therefore, upon successfully completed work, the IDDI has been expanded to IDDI Global Alliance co-chaired by Raymond Benza (Ohio State University, Columbus, USA), Mark Toshner (Papworth Hospital, Cambridge, UK), Sylvia Nikkho (Bayer, Berlin, Germany) and Peter Fernandes (Bellerphon Therapeutics, New Jersey, USA).

Its mission is to get PVD recognised as a global burden of disease in collaboration with international health organisation beside “classical” IDDI topics to be initiated such as challenges of clinical trial design and endpoints, new modalities and technologies, real world evidence, patient engagement, specific features of PH groups, patient engagement and last but not least Covid-19’s impact on PH patients and PVD long-term sequalae.

The Emerging Biotechnology

Consortium (EBC), was initiated in late 2020 under the leadership of Peter Fernandes and Ray Benza, creating workstreams to focus on the development of newer technologies (covering both diagnostics and devices that provide a therapeutic benefit, patient monitoring/care or novel inhalation drug delivery roles. Each workstream will provide EBC members a much needed platform within PVRI and IDDI where the voice of smaller emerging biotechnologies will be heard and acted upon. The EBC is integrated formally within the broader umbrella of the IDDI/Global alliance.

A Note of Thanks

We would like to express our sincere thanks to the dedicated leaders and members of all the four IDDI workstreams. We greatly appreciate the support from all PVRI Roundtable members, who are part of the IDDI.