Report on the European Regulatory Status of Pridopidine for Huntington’s Disease

Executive Summary

A recent recommendation from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has advised against the marketing approval of the experimental oral medication pridopidine for the treatment of Huntington’s disease in adults. This decision represents a significant challenge in the pursuit of new therapies for neurodegenerative disorders, directly impacting progress toward Sustainable Development Goal 3 (Good Health and Well-being). In response, the developers, Prilenia Therapeutics and Ferrer, have affirmed their commitment to further research, aligning with the principles of SDG 9 (Industry, Innovation, and Infrastructure) by planning a new registrational clinical trial to substantiate the therapy’s efficacy.

Regulatory Decision and Implications for Sustainable Development Goals

CHMP Negative Opinion

The CHMP has concluded that the benefits of pridopidine, intended for marketing as Nurzigma, do not outweigh its risks based on the submitted data. The committee’s formal recommendation against approval will be forwarded to the European Commission, which holds the final authority for granting marketing authorisations within the European Union. While the Commission is not bound by the CHMP’s opinion, it typically aligns with its recommendations.

Impact on SDG 3: Good Health and Well-being

The lack of new approved treatments for Huntington’s disease, a debilitating genetic disorder causing progressive nerve cell death in the brain, underscores the challenges in achieving key targets of SDG 3. This goal aims to ensure healthy lives and promote well-being for all, including those with rare and complex diseases. The committee’s decision temporarily halts the availability of a potential new therapeutic option for this patient community.

• Delays access to a potential new therapy for a high-need patient population.
• Highlights the stringent evidence requirements in pharmaceutical regulation, which serve to protect public health but can also slow the introduction of innovative treatments.
• Reinforces the need for continued investment and research to address unmet medical needs in neurodegenerative diseases.

Drug Development, Partnerships, and Innovation

Pridopidine’s Clinical Profile

Pridopidine is an oral small molecule designed to activate the sigma-1 receptor, a protein crucial for nerve cell function and survival. Its development pathway has included several key studies:

1. Phase 2 PRIDE-HD Study: Indicated that pridopidine could slow the progression of functional decline in patients.
2. Phase 3 PROOF-HD Study: Did not meet its primary endpoint of showing a difference in overall functional decline between the treatment and placebo groups. However, a subgroup analysis suggested benefits in motor and cognitive function for patients not concurrently taking antipsychotic or chorea-suppressing medications.

The regulatory application for conditional approval was based on this specific subgroup analysis, which the CHMP ultimately found to be insufficiently robust.

Alignment with SDG 9 and SDG 17

The development and regulatory review of pridopidine are intrinsically linked to several SDGs:

• SDG 9 (Industry, Innovation, and Infrastructure): The research into pridopidine represents a significant investment in scientific innovation aimed at creating new health technologies. The regulatory process itself is a critical part of the infrastructure governing this innovation.
• SDG 17 (Partnerships for the Goals): The collaboration between Prilenia Therapeutics and Ferrer to co-develop and commercialize the therapy in Europe is a clear example of a public-private partnership working towards a common health goal.

Basis for Recommendation and Path Forward

Rationale for Rejection

The CHMP’s primary reason for the negative recommendation was the lack of demonstrated validity and relevance of the subgroup analysis from the PROOF-HD study. The agency concluded that the evidence provided was not sufficient to confirm the efficacy of pridopidine in the proposed patient population (adults with early Huntington’s disease not treated with antipsychotics and/or chorea medicines).

Future Commitments to Research and Development

Despite the setback, Prilenia and Ferrer have announced plans to initiate a new global, potentially registrational, clinical trial to further confirm the safety and efficacy of pridopidine. This commitment to generating more conclusive data demonstrates a continued dedication to achieving the objectives of SDG 3 and SDG 9 by pursuing innovative solutions for complex health challenges. The new study is expected to commence as soon as possible, signaling a resilient approach to pharmaceutical development in the face of regulatory hurdles.

Which SDGs are addressed or connected to the issues highlighted in the article?

SDG 3: Good Health and Well-being

• The entire article focuses on health, specifically the development and regulatory review of a new medication, pridopidine, for Huntington’s disease, a non-communicable neurodegenerative disorder. This directly relates to ensuring healthy lives and promoting well-being for all at all ages. The efforts of companies like Prilenia and Ferrer to bring an “effective therapy to patients” and the role of the European Medicines Agency (EMA) in evaluating its safety and efficacy are central to this goal.

SDG 9: Industry, Innovation, and Infrastructure

• The article highlights the process of pharmaceutical innovation and research and development (R&D). It details the journey of an experimental drug through different phases of clinical trials (Phase 2 PRIDE-HD, Phase 3 PROOF-HD) and the significant investment by private companies (Prilenia, Ferrer) in scientific research. The discussion of “fast track designations” and the plan to launch a “new global study” exemplify the push for innovation within the industrial sector to address health challenges.

SDG 17: Partnerships for the Goals

• The article explicitly mentions a key partnership to achieve the goal of delivering a new therapy. It states, “Prilenia agreed with Ferrer this year to codevelop and commercialize the therapy in Europe and other markets.” This private-private partnership is crucial for pooling resources and expertise for drug development and commercialization. Furthermore, the interaction between these companies and the public regulatory body (EMA) represents a form of public-private engagement essential for achieving health outcomes.

What specific targets under those SDGs can be identified based on the article’s content?

• Target 3.4: Reduce premature mortality from non-communicable diseases

  Huntington’s is a non-communicable disease. The development of pridopidine, which aims to “slowed the progression of functional decline,” is a direct attempt at treatment to improve the quality of life and potentially reduce premature mortality associated with the disease.

• Target 3.8: Achieve universal health coverage, including access to quality and affordable essential medicines

  The article revolves around the regulatory approval process for a new medicine. The goal of the companies is to gain approval to make pridopidine available to patients. The EMA’s role is to ensure that any medicine made available is “safe and effective.” The mention of “orphan drug” status is a mechanism designed to encourage the development of treatments for rare diseases, thereby promoting access to essential medicines for these specific populations.

• Target 3.b: Support the research and development of vaccines and medicines

  The article is a case study of R&D for a medicine targeting a non-communicable disease. It describes the extensive clinical trial process (“PRIDE-HD,” “PROOF-HD”), the investment from pharmaceutical companies, and the use of regulatory mechanisms like “fast track designations” to “expedite a drug’s clinical development and regulatory review.”

• Target 9.5: Enhance scientific research and encourage innovation

  The article details the scientific research process, from the mechanism of the drug (activating sigma-1 receptor) to the execution of large-scale clinical trials. The companies’ decision to “launch a new global study of pridopidine to confirm its benefits” despite the initial setback shows a continued commitment to R&D and innovation in the pharmaceutical industry.

• Target 17.17: Encourage and promote effective public, public-private and civil society partnerships

  The collaboration between Prilenia Therapeutics and Ferrer to “codevelop and commercialize the therapy” is a direct example of a private-private partnership aimed at achieving a common goal. This partnership leverages the strengths of both companies to navigate the complex process of drug development and regulatory approval.

Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

• Rate of disease progression

  This is a direct clinical indicator mentioned in the article. The Phase 2 study suggested that pridopidine “slowed the progression of functional decline,” and the Phase 3 study measured “overall functional decline.” This is a key metric for evaluating the effectiveness of treatments for non-communicable diseases like Huntington’s.

• Motor and cognitive measures

  The article specifies that in subgroup analyses of the PROOF-HD trial, “benefits in motor and cognitive measures observed” were a key finding. These are specific clinical endpoints used to measure the impact of a therapy on the symptoms of a neurodegenerative disease.

• Number of new medicines under regulatory review/approved

  The entire article is about the regulatory process for one new medicine, pridopidine (to be marketed as Nurzigma). The EMA’s decision to “review the application” and the CHMP’s subsequent recommendation are steps in a process that tracks the pipeline of new, potentially essential medicines.

• Investment in research and development (R&D)

  While a specific monetary value is not given, the article implies significant R&D investment through its description of multiple large-scale clinical trials involving hundreds of patients (“more than 400 adults” in PRIDE-HD and “nearly 500 adults” in PROOF-HD) and the plan to launch another “new global study.”

• Number of research and development partnerships

  The article explicitly identifies one such partnership: the agreement between “Prilenia and Ferrer” to codevelop and commercialize pridopidine. This serves as a concrete indicator of collaboration within the industry.

SDGs, Targets, and Indicators Analysis

Source: huntingtonsdiseasenews.com