Niemann-Pick Type C PFDD Meeting Highlights & Next Steps

On March 18, 2019, the Niemann Pick Type C (NPC) community came together for a landmark patient-focused drug development (PFDD) meeting with the Food and Drug Administration (FDA).  Based on the model for PFDD meetings created by the FDA, this meeting focused on two overarching topics: 1) symptoms of NPC and how the disease impacts daily life and 2) current approaches to treating NPC.  A total of 140 people attended the meeting, and over 70 NPC family members were present and many more tuned in to the webcast.  The meeting featured remarks by representative panels of people with NPC and caregivers, presentations by the FDA and an expert NPC clinician, and live-polling discussion sessions with audience members.  The PFDD meeting provided an important opportunity for people with NPC and their caregivers to inform the FDA and developers about their experiences with the disease and their priorities as treatments for NPC are discovered, developed, and reviewed. 

The NPC PFDD meeting organizers are preparing a “Voice of the Patient” report to capture and organize the key elements of the March 18 meeting.  In addition, the report will include data and analysis from a pre-meeting survey completed by 83 people with NPC or their caregivers.  The report will focus on the same overarching topics as the meeting and will note similarities and differences in symptoms and/or treatment approaches across the different ages of onset for NPC: early infantile (0-2 years), juvenile (2-15 years), and adult (>15 years).  The report also will include a section on important findings that the NPC community may use to inform future PFDD activities.  In order to set the stage for the comprehensive information in the report, the meeting organizers have identified several topics to be covered in the following summary.

Symptoms of NPC and Impacts on Daily Life

Panelists, audience members, and survey respondents repeatedly emphasized the daily challenges presented by both the neurological and physical symptoms of NPC, which impact almost all activities of daily living.  They cited cognitive impairment as having a significant impact giving examples such as NPC patients understanding speech but having difficulty forming sentences or having trouble with school work that previously posed no difficulty.  In addition to cognitive challenges, many individuals with adult-onset NPC also experienced psychological symptoms that might be mistaken for bipolar disorder or schizoaffective disorder.

Several meeting participants spoke about how NPC impacts a person’s ability to walk or run.  As NPC progresses, many patients rely on devices including canes, walkers, and wheelchairs for mobility.  For many participants, a particularly worrisome aspect of the movement challenges was cataplexy and the likelihood of associated falls.  Difficulty in swallowing, aspiration, and seizures also were cited as symptoms that patients find burdensome as the NPC condition progresses.

A common theme echoed by many is the difficulty diagnosing this disease.  This concept is supported by the survey data: about half of survey respondents indicated that they had received at least one incorrect diagnosis before NPC was accurately diagnosed.  Specific symptoms that often led to a correct diagnosis were an enlarged spleen at birth and neurological symptoms.  For many meeting participants, one symptom alone did not lead to a diagnosis.  Instead, the coexisting, seemingly unrelated, symptoms provided the necessary clues.  The heritable nature of NPC also means that many patients were diagnosed, sometimes even when they were pre-symptomatic, because a sibling showed symptoms and was diagnosed first.

Current Approaches to Treating NPC

Meeting participants and survey respondents indicated that they—or the NPC patient they represented—have taken a variety of medications and experimental drugs to help manage the disease.  Per FDA guidelines, meeting participants were asked to avoid referring to brand-name drugs or specific clinical trials.  Two types of drugs that many NPC patients have tried, including those who are pre-symptomatic, are cyclodextrins and miglustat.  Many patients also have used anti-seizure and anti-cataplexy drugs to manage their disease. 

PFDD meeting participants and survey respondents also use medical devices to help manage NPC.  As mentioned above, many patients require devices to help them walk or rely on wheelchairs when they can no longer walk.  Many patients and caregivers also reported that a gastronomy tube (G-tube) was needed when swallowing became difficult.  Several panelists and meeting participants spoke about their children’s resistance to having to rely on such devices as they became less able to carry out everyday activities without assistance.

Although the focus of the meeting was current approaches to treating NPC, both the meeting and the pre-meeting survey also provided opportunities to solicit input on what patients and caregivers hope future treatments will achieve.  Reducing neurological symptoms was the most frequently requested benefit, more so than reducing physical symptoms or extending life span.  Live-polling results at the meeting indicate that the activities of daily living patients and caregivers would most like to see preserved or restored are eating/drinking and the ability to participate in social activities.  These points were reinforced by comments from caregivers who expressed hopes that their children could live their lives to the fullest just like children without NPC.

Other Points

Meeting participants and survey respondents raised other important details about the NPC experience.  Examples of these topics are included below and will be described further in the Voice of the Patient report.

  • The need for improved screening and specifically a new born screen, as well as diagnostic approaches to allow for earlier disease intervention.
  • Members of the NPC community are very supportive of research and the unmet medical needs of patients makes them eager to participate in trials and other research opportunities.  They frequently expressed a willingness to take substantial risk in order to advance therapy development and hopefully achieve a better quality of life; something that may be more deeply understood in the community’s future PFDD work.
  • Unlike in many other rare disease communities, there is a high level of exposure to experimental therapies through trials and expanded access programs.  This reality will need to be considered as a part of the overall strategy for NPC therapy development.

Stay tuned for the forthcoming Voice of the Patient report (anticipated publication August 2019).