The negotiated delay, in getting access to our data, is not doing us any favors in getting our BLA completed. Aaron, on YMB has posted several reasons why this delay weakens our position. I found his latest post drives one point home, with eye opening clarity. At the very least, we need to know if this data even exists. If not, the BLA might be much farther, from reach, than we hope. This is the kind of information they may not be able to reconstruct by revisiting the documentation from the original trial sites. Please, comment freely about this.
Aaron
"FROM PAGE ONE RTF:
To Cytodyn Inc:
Attention:Kazem Kazempour, PHD
Regulatory agent on behalf of Cytodyn
20201 Century Blvd, 4th floor Germantown, MD, 20874
NOTE THE ADDRESS IS FOR AMAREX AND LETTER IS ADDRESSED TO AMAREX CEO
FROM PAGE 8 OF RTF:
Submission of Unagreed Upon Population PK (Pop PK) Analysis:
A thorough assessment of dose selection is critical to ensure the safe and effective use of drugs. Methodologies such as Pop PK analysis are used to assess dose selection and to evaluate the impact of intrinsic and extrinsic factors on drug exposure. Hence, it is critical that the data used to build and validate population pharmacokinetic models are robust. Therefore, we requested a Pop PK analysis to support the selection of a higher dose [700 mg, based on the dose-finding study in the monotherapy study (CD03)] than the dose evaluated in the pivotal trial (CD02), because you only analyzed the PK data at the proposed dose (700 mg) using Pop PK analysis method. In your correspondence dated January 16, 2019, you described plans to use studies CD02, CD03, and CD06 studies for the Pop PK model development and covariate analysis. Rather than submitting a Pop PK analysis as described in that correspondence, the submitted analysis in your BLA includes data from CD02, CD03, and Study 2101 without a clear rationale for including the results from study 2101 and excluding the results from trial CD06. Of note, the formulation used in Study 2101 (formulation two) is significantly different from the formulation used in CD02, CD03, and CD06 (formulation four) and the current PK sampling times across the formulations do not support a comparative test via Pop PK. In the absence of comparability data between formulations two and four, a substantive review of the Pop PK analysis to assess the proposed dosing regimen cannot be conducted."
Aaron
"FROM PAGE ONE RTF:
To Cytodyn Inc:
Attention:Kazem Kazempour, PHD
Regulatory agent on behalf of Cytodyn
20201 Century Blvd, 4th floor Germantown, MD, 20874
NOTE THE ADDRESS IS FOR AMAREX AND LETTER IS ADDRESSED TO AMAREX CEO
FROM PAGE 8 OF RTF:
Submission of Unagreed Upon Population PK (Pop PK) Analysis:
A thorough assessment of dose selection is critical to ensure the safe and effective use of drugs. Methodologies such as Pop PK analysis are used to assess dose selection and to evaluate the impact of intrinsic and extrinsic factors on drug exposure. Hence, it is critical that the data used to build and validate population pharmacokinetic models are robust. Therefore, we requested a Pop PK analysis to support the selection of a higher dose [700 mg, based on the dose-finding study in the monotherapy study (CD03)] than the dose evaluated in the pivotal trial (CD02), because you only analyzed the PK data at the proposed dose (700 mg) using Pop PK analysis method. In your correspondence dated January 16, 2019, you described plans to use studies CD02, CD03, and CD06 studies for the Pop PK model development and covariate analysis. Rather than submitting a Pop PK analysis as described in that correspondence, the submitted analysis in your BLA includes data from CD02, CD03, and Study 2101 without a clear rationale for including the results from study 2101 and excluding the results from trial CD06. Of note, the formulation used in Study 2101 (formulation two) is significantly different from the formulation used in CD02, CD03, and CD06 (formulation four) and the current PK sampling times across the formulations do not support a comparative test via Pop PK. In the absence of comparability data between formulations two and four, a substantive review of the Pop PK analysis to assess the proposed dosing regimen cannot be conducted."
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