Certara.com

Modeling and Simulation Supports Competitive Product Profile
Assessment and In-Licensing Decision for Diabetes Compound
Modeling Strategy Provided Sponsor Timely and Compelling Support for
Positive Efficacy Signal of In-Licensing Candidate, Helping to Secure $23
Million Financing Round and Advance Compound to Phase IIB

Background: A specialty pharmaceutical company was seeking to provide rapid, quantitative
support to fund its in-licensing strategy for an oral Type 2 anti-diabetic agent. Limited data from a
single Phase IIa study was available on the drug candidate.
Challenge: As the sponsor worked to finalize its in-licensing strategy and secure deal terms, it
became critical to provide investors with rapid yet rigorous early quantitative support for the
potential of the compound’s efficacy and safety profile versus currently marketed oral diabetes
treatments, notably Avandia (rosiglitazone) and Actos (pioglitazone). In the absence of
randomized controlled trials that directly compared the drug candidate’s performance to that of
established competitors, making an “apples to apples” assessment would be particularly
challenging.
Solution: First, Pharsight developed models of the diabetes treatment landscape for key clinical
endpoints (e.g., FPG and HbA1c) using its in-house database of mean trial results from publicly
available data sources. Public-source references extracted from the database for modeling
included FDA Summary Basis of Approval (SBA) documents for Avandia and Actos, as well as
relevant articles from the published scientific literature The literature-based disease models
described the relationship of FBG and HbA1c as a function of time, and also accounted for the
differences in response due to factors such as disease baseline value, dose, patient
characteristics, and run-in length of monotherapy trials. The models were then simulated to
generate predictions of competitor trial arms that matched the exact characteristics of the
available Phase IIa trial data for the drug candidate. Finally, the existing Phase IIa data from the
drug candidate’s short-term trial (e.g., at 4 weeks) were compared with the matched, model-
based simulations for Avandia and Actos to facilitate a robust evaluation of the NCE’s early
efficacy signal. A similar analysis was performed for key safety endpoints.
Benefit: The model-based meta analysis established the NCE’s parity with, and at higher doses
superiority to, its competitors based on efficacy. This approach enabled the sponsor to simulate
active control arms for the NCE that hadn’t yet been run – in effect to conduct virtual “head to
head trials” to demonstrate the compound’s clinical and commercial potential.
Impact: The sponsor secured a $23 million round of financing to successfully in-license the
compound and initiated a Phase IIb trial1. The modeling and simulation strategy helped the
sponsor provide rigorous and timely support of a positive efficacy and safety signal for the drug
candidate versus competing treatments to support their in-licensing strategy and advance the
compound with greater confidence into later-stage clinical development2.
1 Sponsor press releases and data on investigational program.
2 The literature-based models developed to support the in-licensing decision also offer the potential to be extended and combined with Phase IIb NCE data to support downstream trial design and program strategy decisions (e.g., making predictions about steady-state HbA1c response to facilitate the design of pivotal trials).

Source: http://www.certara.com/images/uploads/files/Diabetes_Case_Study_Modeling_and_Simulation_Supports_Competitive_Product_Profile_Assessment_and_In-Licensing_Decision.pdf