Economic Benefits

How does Xceleron Reduce the time and Expense of Pharmaceutical R&D?

Xceleron has demonstrated that the combination of robust analytical chemistry with AMS detection can save significant time and development expense. The majority of our experience is with human therapeutic doses by the intended therapeutic dose route.  Certain generalizations apply with regard to clinical PI de-risking and PII/III removal from the critical path and are discussed below.

More asset-related examples exist for the preclinical development of complex molecules such as antibody-drug conjugates.  In such cases 14C and AMS are used to understand the disposition of payload as distinct from payload and associated conjugates. Asset-related examples also exist to describe how 14C and AMS have been used in the choice of congeners for full human development. Please contact Xceleron for more information.

 


Application of 14C and AMS Detection in reducing the time and Expense of Pharmaceutical R&D

De-risking the critical path

 


Human AME – Conventional Approach

Human AME – Conventional Approach

Human AME – Xceleron Approach

Human AME – Xceleron Approach

Human absorption metabolism excretion (AME) studies are typically conducted to satisfy a regulatory requirement.  Traditionally human AME studies were conducted using a large amount (macrotracer c.100uCi per subject) of 14C labeled drug to overcome the limited sensitivity of liquid scintillation counting (LSC) in clinical sample analysis.  Increasingly, high sensitivity AMS is being used to measure 14C labeled drug in human AME studies.  The study is conducted using significantly lower amount of 14C (microtracer c.1uCi per subject) which can reduce the length and expense of the investigation by more than seven months and $0.45MM, respectively. This is possible because :

  1. Non-GMP 14C label can be used where the 14C labeled component is less than 0.15% of the total drug mass dose
  2. Animal dosimetry studies are not required to support the radiolabel dose administration to humans
  3. No formal approval is required from radiological protection agencies for such low doses of radioactivity to humans

 


Human PK – Conventional Approach

 Human PK – Conventional Approach

Human PK – Xceleron Approach

Human PK – Xceleron Approach

Knowledge of the pharmacokinetic behavior of drugs and in particular their absolute bioavailability has been requested by regulators in America and Europe. In Australia, knowledge of absolute bioavailability is required for registration.  Xceleron’s customers are also using knowledge of pharmacokinetic parameters such as absolute bioavailability, clearance and volume of distribution to guide their early treatment of oncology patients and women of child-bearing age and to inform drug product manufacturing decisions.

Investigations of pharmacokinetic parameters were traditionally conducted using a cross over (extravascular-washout-IV) design with unlabeled drug.  This approach has been calculated as requiring an additional 12 months and $2MM.

Xceleron pioneered the use of a concomitant extravascular and 14C IV microtracer clinical design.  This approach is better scientifically because there are no temporal effects and it saves six months and $1.5MM compared to the conventional design because:

  1. Formulation of the IV dose is significantly reduced as very low doses (10ug) can be used
  2. No specific IV toxicology is required because toxicology enabling the extravascular therapeutic human dose also covers the tiny sub-therapeutic IV mass dose
  3. Clinical costs can be significantly reduced by incorporating the IV microtracer into an existing clinical study e.g. Phase I SAD/MAD, food effect
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