Omeros Corporation: OMS721

The data presented in BLA 761152 fails to demonstrate substantial evidence of effectiveness for OMS721 for the treatment of hematopoietic stem cell transplantationthrombotic microangiopathy (HSCT-TMA).

It appears you are attempting to establish substantial evidence of effectiveness by proposing a single adequate and well-controlled trial plus confirmatory evidence, instead of two adequate and well-controlled trials.

The LDH response was transient, and tacrolimus was stopped the same day as OMS721 so we cannot conclude that the LDH response or renal response was due to OMS721.

Your application does not contain sufficient data that could serve as confirmatory evidence of effectiveness.

Although there appears to be partial attenuation of complement activation and a delay in thrombotic onset by OMS721 in animal and in vitro models, you have not shown evidence that this translates into a measurable clinical benefit, either directly or indirectly.

HSCT-TMA by a sufficient magnitude to persuasively demonstrate a clinical benefit.

In addition, if you use only a single adequate and well controlled trial to support your BLA, you will also need to provide adequate confirmatory evidence; what this evidence will consist of can be discussed in a post action meeting.

For example, if the current trial in atypical Hemolytic Uremic Syndrome (aHUS) were to be successful, that data might be used as confirmatory evidence for HSCTTMA.

We have the following comments/recommendations that are not approvability issues, but that you should address in subsequent discussions and/or a resubmission:

The PK sampling design and the collected PK data from clinical studies were not informative enough to allow for a reliable assessment of the effect of PE on OMS721 clearance, thus impeding our ability to verify the proposed OMS721 supplemental dose of 2 mg/kg.