Replies to post #494894 on Anavex Life Sciences Corp (AVXL)

[Investor2014]

From the EMA opinion on pridopidine - the closest match in category and MoA at present to A2-73.:

How does Nurzigma work?
The active substance in Nurzigma, pridopidine, activates a protein called sigma-1 receptor (S1R). S1R
is found inside the cells and is involved in cellular processes that contribute to the health and survival
of nerve cells. By activating S1R, pridopidine was expected to improve cellular processes that are
involved in nerve cell damage and Huntington’s disease.

What did the company present to support its application?
The company presented results from a main study involving 499 adults aged 25 years and older with
early Huntington’s disease. Patients in the study were given either Nurzigma or placebo (a dummy
treatment). The main measure of effectiveness was the change in the total functional capacity (TFC)
score after 65 weeks of treatment. The TFC score measures how well a person with diseases that affect
the nervous system can perform daily tasks and activities. The company also presented results from
analyses in a subgroup of 208 patients from the main study, namely adults with early Huntington’s
disease who were not treated with antidopaminergic medicines. In addition, the company presented
results from 3 supportive studies in adults with Huntington’s disease.

What were the main reasons for refusing the marketing authorisation?
The Agency considered that the main study and the supportive studies failed to provide evidence that
Nurzigma is effective in patients with early Huntington’s disease. The Agency noted that the validity
and relevance of the results of the analyses in the subgroup of patients (adults with early Huntington’s
disease who were not treated with antidopaminergic medicines) from the main study have not been
demonstrated.

Therefore, the Agency’s opinion was that the effectiveness of Nurzigma had not been demonstrated.
Although the company applied for a conditional marketing authorisation, the medicine did not meet the
criteria for granting this type of authorisation. As a result, the Agency recommended refusing the
conditional marketing authorisation.

Once sponsor's analysis stray off the clinical trial protocol it makes approval more difficult. In this case the primary endpoint failed and the company tried to justify approval in subgroups analysis outcomes.

I will stick with my likely too generous 25% chance of approval for A2-73 based on existing trials data - until perhaps we see an EMA clock restart indicating that at least Anavex were able to provide LoQ answers complete enough to continue the review process, which includes of course a deep dive into LoQ responses.

NAARDEN, Netherlands & WALTHAM, Mass. & BARCELONA, Spain--(BUSINESS WIRE)-- Prilenia Therapeutics B.V. and Ferrer today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the refusal of the marketing authorization for pridopidine’s marketing authorization application for Huntington’s disease (HD).

We are disappointed, but undeterred in our commitment to bring what we believe is an effective therapy to patients and will explore all options collaboratively with regulators.

Prilenia and Ferrer are focused on bringing pridopidine to people living with HD and amyotrophic lateral sclerosis (ALS) worldwide as quickly as possible. Near-term plans are in place to initiate a potentially registrational global HD study, to provide confirmation of the previously observed pridopidine results, and a pivotal global Phase 3 ALS study, with recruitment for both expected to start as soon as possible.

Prilenia is now planning to initiate a confirmatory / registrational study in HD. The kind of study Anavex originally planned to initiate in parallel with discussing an approval path with regulators based on the P2b/3 trial results. I wish Anavex had done as they said they would instead of Missling's pennywise pound foolish approach that risks a big set back.