Anavex Life Sciences Corp (AVXL)

[XenaLives]

More on the Japanese accelerated approval program:

Criteria for designation

Regenerative medical products for diseases in urgent need of innovative therapy that may satisfy the following four conditions:

 
 1. Innovativeness of the products,with novel mechanism of action; 
 2. The target medical condition should be one of the following: 
     a. serious or life threatening medical condition; or 
     b. medical condition with persistent symptoms (conditions  
     interfering with normal activities of daily  living)  
     for which there is no other curative treatment 
 3. Highly effective treatment against the target medical condition. There is no other therapy for the target medical condition, or the symptoms of patients 
  are expected to be significantly improved through use of the product as compared to the efficacy of existing therapies (including the case where 
  safety is expected to be improved significantly); 
 4.  Develop the product rapidly and file an application for approval in Japan, ahead of other countries. The sponsor of the product intend to file an initial  
 application for approval in Japan, including the case where simultaneous applications are planned to be made in both Japan and other countries. 
  

Advantage of designation

The SAKIGAKE designation system should allow the production of innovative medical products ahead of other countries with the shortest possible development and
review process. The following measures shall be used:
1. Consistent prioritized consultation by the Pharmaceutical Medical Devices Agency (PMDA);
2. Preapplication consultation in which de facto review is started with data that can be submitted before the application for approval;
3. Prioritized review aiming for a further reduction in the total review period (target total review time is 6 months);
4. Assigning a manager as a concierge. Concierge coordinates sponsor and MHLW/PMDA to toward approval including conformity assurance,
quality management, safety measures and review;
5. Strengthening postmarketing safety measures including the extension of the reexamination period.

Preapplication consultation includes the following five menus:
1. Quality;
2. Nonclinical;
3. Clinical including plan for postmarketing data collection;
4. Good Clinical Practice (GCP)/ Good Laboratory Practice (GLP) compliance; and
5. Good Gene, Cellular and Tissuebased Products Manufacturing Practice (GCTP) compliance. After the PMDA’s de facto review and onsite inspection,
the sponsor of the product files the application for approval in Japan (Table 1).

Steps for the SAKIGAKE designation Under the current framework, MHLW solicits candidate products
that satisfy the above criteria, and conducts a hearing on the candidate products in preparatory evaluation. The potential candidates meeting these specified criteria are invited to apply as candidates
for SAKIGAKE designation. MHLW evaluates the applied products based on priorities set through review of the applications by PMDA and the products judged to be excellent are selected or SAKIGAKE designation. MHLW reports to the Pharmaceutical Affairs and Food Sanitation Council and then designation results are made public. After the three rounds of applications, nine regenerative medical products (Table 2), 16 pharmaceuticals, six medical devices and one in vitro diagnostic have been assigned for SAKIGAKE designation [10].


ACCELERATED DEVELOPMENT OF INNOVATIVE REGENERATIVE MEDICAL PRODUCTS
Early approval system for regenerative medical products On November 2014, the Pharmaceutical Affairs Law was revised and renamed the Pharmaceuticals, Medical Devices and Other Therapeutic Products Act (PMD Act) [11]. Regenerative medical products are defined as:
1. Processed (more than minimal manipulation) live human/animal cells that are intended to be used for either:
a. The reconstruction, repair or formation of structures or functions of the human body; or
b. The treatment or prevention of human diseases
2. Gene therapy The regenerative medical prod ucts considered are mainly those satisfying unmet medical needs (serious or life threatening illnesses). Given that, in regenerative medicine products, there is a high vari ability in the quality of cells, manufacturing capacity, mechanism of action, number of patients with the target medical condition, clinical positioning of products etc., it would require longterm collection of clinical data for confirmation of effectiveness and safety. The PMD Act provides the option of a new pathway to obtain conditional and time-limited approval for regenerative medical products to achieve the early practical application. To obtain conditional and time limited approval, exploratory clinical trials are required that predict a reasonable likelihood of clinical benefit (for example, by using a surrogate endpoint). Following the conditional and time-limited approval, a confirmatory clinical study and followup patient safety measures are required to prepare for a further approval process within a maximum period of 7 years. Toward the full approval (second approval) review after the conditional and time-limited approval (first approval), it is necessary to construct a feasible plan to confirm effectiveness and safety before the expiration of conditional and time-limited approval. In order to ensure that products with uncon firmed effectiveness do not remain on the market, the new regulation gives MHLW a clear legal author ity to withdraw approval during the second approval process. In September 2015, HeartSheet, a skeletal myoblast sheet product for the treatment of severe heart failure, was the first product granted conditional and time-limited approval [12] (available online; for assessment report see [13]). The regenerative medical products that received SAKIGAKE designation as regenerative medical product targets for a serious or life threatening medical condition are good candidates to obtain conditional and time-limited approval.

insights.bio/cell-and-gene-therapy-insights/wp-content/uploads/sites/2/2018/07/Maruyama-Expert-Insight.pdf