LONDON (ShareCast) - (Sharecast News) - Commercial-stage pharmaceutical company Shield Therapeutics updated the market on the 'AEGIS-H2H' clinical trial on Tuesday, the data of which was primarily designed to be used in health economic analyses, pricing and reimbursement applications, as well as marketing purposes.
The AIM-traded firm said the update had no impact on existing marketing authorisations in the EU, the US and Switzerland, nor on any approved prescribing information, adding that the data from the AEGIS-H2H study had not been used in any of the regulatory submissions that led to the approval of 'Feraccru' and 'Accrufer' in either Europe, the US or Switzerland .

It explained that, based on a range of positive clinical trials, Feraccru and Accrufer was approved for the treatment of iron deficiency in adults with or without anaemia in those three territories.

Commercial partners including Norgine and Beijing Aosaikang Pharmaceutical had licensed the rights to the products in the European Union, Australia, New Zealand and China, with a partnering process for the commercial rights in the Us currently being conducted.

The company said it was continuing to work "diligently" towards the appointment of a suitable commercial partner.

On 4 March, Shield announced that the AEGIS-H2H clinical trial had delivered positive results, demonstrating that Feraccru and Accrufer was "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 and 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.

"The above statement was made in relation to the 'per protocol' (PP) analysis of the study results," Shield explained on Tuesday.

"These data have been published and presented at both the United European Gastroenterology Week (UEGW) and European Crohn's and Colitis Organisation (ECCO) scientific congresses.

"The PP analysis 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 endpoint was measured."

With an open-label design, as was used in the study, the true efficacy of the different oral and intravenous treatment arms was better determined by using the PP population, which accounted for low compliance and early withdrawal, the board explained, whereas the 'intention to treat' (ITT) population was liable to overestimate the adverse events and underestimate the efficacy of the oral agent, as those were given via daily administration, whereas the comparator is administered as a bolus dose.

"The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) advises caution in the use of ITT analyses in non-inferiority trials.

"Therefore, it was decided to use the PP population for the primary efficacy analysis."

However, Shield said the pre-defined success criteria of the 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 the target.

"In the ITT analysis, which refers to all patients who were randomised into the study, whether or not they completed the entire 12-week period and fully complied with the study design, Feraccru [and] Accrufer clearly demonstrated effectiveness, but did not achieve non-inferiority compared to the IV iron therapy," the board said.

"The 4 March 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 that finding, which Shield said had just come to light, the board had instigated an immediate independent review into the analysis of both datasets, which was being overseen by a non-executive director.

The company said it would update the market on the review in due course.

"As stated above, 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 and Accrufer in either Europe, the US 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 and Accrufer is an important treatment alternative for many patients, combining efficacy with good tolerability, without the need for hospital administration."

In the meantime, Shield said it was working closely with its commercial partners to ensure relevant information was "clearly communicated" to all stakeholders in a timely manner.

At 1421 GMT, shares in Shield Therapeutics were down 41.84% at 57p.

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