Shield Therapeutics plc (LSE: STX) has provided an update and clarification relating to the AEGIS-H2H clinical trial.
On 4 March 2019, Shield announced that the AEGIS-H2H clinical trial had delivered positive results, demonstrating that Feraccru®/Accrufer® is non-inferior to a market-leading intravenous (IV) iron therapy in treating iron deficiency anaemia in adults with inflammatory bowel disease (IBD).
The announcement stated that primary analysis of the AEGIS-H2H study demonstrated the response to Feraccru®/Accrufer® at 12 weeks was within 9% of the response seen with the IV iron therapy and within the 20% limit required by the study protocol to confirm non-inferiority (p = 0.022, subsequently adjusted to p = 0.017 after detailed analysis).
The above statement was made in relation to the per protocol (“PP”) analysis of the study results and refers to those patients who fully complied with the study design and remained on the study for the full 12-week period, at the end of which the primary end point was measured.
With an open-label design, as was used in this study, the true efficacy of the different oral and intravenous treatment arms is better determined by using the PP population, which accounts for low compliance and early withdrawal, as opposed to an intention to treat (“ITT”) population that is liable to overestimate the adverse events and underestimate the efficacy of the oral agent as these are given via daily administration, whereas the comparator is administered as a bolus dose.
However, the pre-defined success criteria of this clinical study, as set out in the statistical analysis plan, inadvertently required that ferric maltol could be considered non-inferior to IV iron if the difference in the proportion of responders in each arm at week 12 was less than 20% in both the ITT and the PP analyses, but should have allowed for non-inferiority if either the PP or ITT populations achieved this target. The 4 March 2019 announcement should therefore have made it clear that the study did not achieve non-inferiority in both of the ITT and PP analyses.
In light of the above finding which has just come to light, the Board has instigated an immediate independent review into the analysis of both datasets, which is being overseen by a non-executive director. The Company will update the market on this review in due course.
Importantly for shareholders, this clarification has no impact on existing marketing authorisations, nor on any approved prescribing information and the data was not used in the regulatory submissions that led to the approval of Feraccru®/Accrufer® in either Europe, the USA or Switzerland. Shield remains confident that data from the AEGIS-H2H study including the long term extension results, together with the existing positive efficacy and safety data on the product provide compelling evidence that Feraccru®/Accrufer® is an important treatment alternative for many patients, combining efficacy with good tolerability, without the need for hospital administration.
Shares in Shield are currently trading down 56% following this clarification announcement