As background, particularly in the area of rare disease, disease-specific patient organizations play a crucial role in helping to driving forward the development of treatments.
These patient organizations can be a valuable source of disease knowledge and data, of patients for clinical trial participation, sometimes of funding, of advocacy when dealing with regulatory authorities and of a patient market, if and when a treatment is developed.
For fellow-ASX biotech, Neuren, the role of patient organizations was vital in its development of a therapeutic for Rett syndrome and this continues to be the case with the other four rare diseases that Neuren is now pursuing.
ADPKD is fortunate to have such an organization, the PKD Foundation, an NFP that funds research, advocates for patients, and builds a community for those impacted by polycystic kidney disease. The Foundation has also established a registry of ADPKD patients with 2774 patients registered as of last year.
Another important aspect in rare disease development is educating regulatory authorities on the disease, its impact on the lives of patients and families and what the greatest needs are from the patient and family’s perspective.
One of the ways in which this can happen is through FDA-led Patient Focused Drug Development (PFDD) Meetings as well as Externally-led PFDD Meetings. In April this year, a PFFD was held for ARPKD.
Another way in which regulatory authorities have been engaged for PKD was a PKD Regulatory Summit held in May 2021, which brought together representatives from academia, industry, regulatory agencies (FDA and EMA), and the patient community to discuss the unmet needs in ADPKD and ARPKD drug and regulatory development. The conference was organized by the PKD Outcomes Consortium from Critical Path Institute in partnership with the PKD Foundation*. The issues discussed at the summit covered topics including obstacles to drug development for early ADPKD and ARPKD, clinical trial design in ADPKD, development of novel biomarkers for disease progression, development of clinical outcome assessment tools, and disease progression modelling. Summaries of topics covered at this summit were subsequently published and can be found here,here and here.
Use of accelerated and conditional approval pathways for ADPKD was one of the topics discussed and the summary of the discussion provides evidence that Rohan’s planned accelerated pathway to regulatory approval for PYC-003 is not a pipe dream – this pathway is actually encouraged.
Tolvaptan’s approvals in 2015 and 2018 by Health Canada, the European Medicines Agency (EMA) and the US Food and Drug Administration, respectively, were on the basis in the clinical studies of positive outcomes for a combination of surrogate end points (eGFR, TKV, and kidney pain) in ADPKD (9). Developers should consider using accelerated and conditional approval pathways that leverage the use of surrogate end points with a study that can be conducted in a timely fashion while generating an interpretable and confirmable result. Negotiations with HAs have set a precedent for using a reasonably likely surrogate efficacy biomarker (TKV) toward accelerated approval after an interim analysis, with full approval contingent on the success of an accepted clinical end point (e.g., 30% decline in eGFR by the conclusion of the trial) (3). HAs expressed the importance of taking measures to ensure the completion of the full study cohort, despite patients potentially having access to the drug commercially during the confirmatory portion of the ADPKD study. Studies should be fully enrolled at the time of the accelerated approval and have measures in place to address any missing patient data due to dropouts. Although TKV has not been validated in the pediatric population as a prognostic surrogate, children with increased TKV experience early hypertension and an accelerated rate of kidney growth (10).
* Funding for the 2021 PKD Regulatory Summit was provided by Otsuka Pharmaceutical and the PKD Foundation. Critical Path Institute is supported by the Food and Drug Administration (FDA) of the US Department of Health and Human Services (HHS) and is 54.2% funded by FDA/HHS, totalling $13,239,950, and 45.8% funded by nongovernment source(s), totalling $11,196,634.
PYC Price at posting:
7.3¢ Sentiment: Hold Disclosure: Held
(20min delay)