Pridopidine now under review in Europe as Huntington’s treatment
Prilenia seeking approval of oral therapy to slow disease progression
The European Medicines Agency (EMA) has agreed to review Prilenia Therapeutics’ application seeking approval of pridopidine, an oral therapy candidate for adults with Huntington’s disease, the company announced.
The regulatory application is based on safety and efficacy data from pridopidine’s clinical development program, which showed the therapy has the potential to slow Huntington’s progression.
“Pridopidine has delivered consistent efficacy benefits across multiple key measures of HD [Huntington’s disease] and has demonstrated a placebo-like safety profile in a large safety database,” Michael R. Hayden, PhD, CEO of Prilenia, said in a company press release. “We have submitted a compelling suite of evidence and pridopidine presents the opportunity for a much-needed paradigm shift in HD therapy.”
The submission follows positive discussions with European regulators on a potential path for approval for the twice-daily therapy. Given that the EMA’s review process typically takes about 12 to 14 months, the treatment, should it be approved, could be available to patients as soon as the second half of 2025.
A potential path for pridopidine’s approval is also being discussed with the U.S. Food and Drug Administration, and Prilenia is considering regulatory submissions in other countries once the review process in Europe is complete.
Pridopidine is also on a fast track for US approval
Pridopidine was granted orphan drug status both in the European Union and the U.S. for the treatment of Huntington’s, and was also given fast-track designation in the U.S. These designations are meant to accelerate the therapy’s clinical development and regulatory review.
The EMA’s decision to review the treatment for potential approval was welcomed by patient advocacy groups.
“We applaud the progress regulators are making in trying to support the urgent needs of people with HD,” said Astri Arnesen, president of the European Huntington Association. “If we can come out of the other end of this process with a new therapeutic approach, offering the potential to slow down disease progression, we will have taken a huge step forward for the whole community.”
Huntington’s is caused by a mutation in the HTT gene, which contains a region where three DNA building blocks — C, A, and G — are repeated 10 to 35 times. People with Huntington’s have an excessive number of CAG repeats, often 40 or more, resulting in a longer than usual huntingtin protein.
This abnormally long protein is prone to forming toxic clumps inside nerve cells, disrupting their function and eventually causing their death. The neurodegenerative disease is characterized by motor, psychiatric, and cognitive symptoms.
Pridopidine is an orally available small molecule that’s able to reach the brain and spinal cord, and works by binding and activating the sigma-1 receptor. This protein regulates a range of cellular pathways essential for nerve cell function and survival that are commonly impaired in Huntington’s.
Thus, the treatment is designed to help ease disease symptoms and slow its progression.
Pridopidine could, for the first time, provide an option that may slow down decline in several functionally relevant disease domains and thus potentially offer patients and their families an extension to the quality time they have together.
In the Phase 2 PRIDE-HD clinical trial (NCT02006472), which enrolled 408 adults with Huntington’s, twice-daily treatment with pridopidine at a dose of 45 mg worked better than a placebo at slowing patients’ functional decline.
However, the subsequent Phase 3 PROOF-HD trial (NCT04556656), which involved 499 adults with early Huntington’s, failed to confirm pridopidine’s superiority over a placebo.
Still, subgroup analyses indicated the therapy could slow disease progression in patients who were not on antipsychotics or medications for chorea, which are the involuntary, jerky movements that are a hallmark of Huntington’s. Importantly, benefits were seen among both motor and cognitive measures.
“Pridopidine could, for the first time, provide an option that may slow down decline in several functionally relevant disease domains and thus potentially offer patients and their families an extension to the quality time they have together,” said Ralf Reilmann, MD, a neurologist and the founding director of the George-Huntington-Institute in Muenster, Germany. “Since its safety profile appears favorable and it is taken orally, pridopidine can be easily made available to patients.”
Prilenia also is evaluating pridopidine as a potential treatment for amyotrophic lateral sclerosis, another progressive neurodegenerative disease.
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