Summary

• Omeros' OMS721 is in Phase III trials for 2 disorders.
• OMS721 just was awarded FDA Breakthrough Therapy Designation for yet another disorder; to treat patients at significant risk of dying after Hematopoietic Stem Cell Transplant.
• Many expect the FDA to short-circuit the normal procedure and get this life-saving treatment on the market, without the need of a Phase III trial.

INTRODUCTION
Omeros' (NASDAQ:OMER) MASP-2 Inhibitor drug candidate, OMS721, already enrolled in FDA accelerated programs for 2 indications, was recently awarded Breakthrough Therapy Designation (BTD) for treatment of High-Risk Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (abbreviated HSC-TMA or HSCT-TMA).

These patients often have serious, life threatening co-existing conditions, and mortality rates have been reported to be as high as 100 percent. As reported previously, the estimated median survival for OMS721-treated patients was an order of magnitude greater than that for a matched historical control (p<0.0001). Further analysis of the data examined 100-day mortality, an important endpoint previously used as an approval endpoint in HSCT. That analysis also showed that OMS721-treated patients had improved survival relative to the historical control (53% vs 10%; p = 0.0002).

FOCUS
Many Omeros shareholders have been wondering how the latest FDA action will affect the amount of time it will take before OMS721 can be marketed to save the lives of high-risk HSC-TMA patients. There seems to be an expectation that the FDA may grant early approval based upon the FDA special program called "Accelerated Approval"

In this article, I am going to suggest that, based upon a recent read of the FDA AA program details and the latest information from Omeros, OMS721 does not need the typical benefit of the AA program and may be approved is short order.

FACTS & ANALYSIS

1. AA provides an accelerated path to MARKETING approval and ultimately FULL approval. I am going to refer to these two types of approval by the capitalized words to be clear of what I mean.

Keep in mind that Omeros was recently granted BTD, not AA.

2. AA's biggest help to a drug candidate is to allow the use of a surrogate endpoint.

As reported by Omeros, patients treated with OMS721 demonstrate significant improvement in the biomarkers of the condition/disease. These biomarkers (mean platelet count and mean levels of lactate dehydrogenase and haptoglobin) can be considered surrogate endpoints.

But OMS721 for HCS-TMA does not need to be evaluated on the basis of surrogate endpoints.

Overall Survival is the ultimate endpoint. In cancer and research on treatment of life-threatening diseases, the standard primary endpoint is how long the patients survive after treatment. For the transplant patient population with HSC-TMA that does not respond to cutting immunosuppressive dose, the end is not long in coming.

3. For a drug candidate granted AA status, the FDA would normally look at the surrogate endpoint data to decide whether there was enough evidence that the drug works and would not do more harm than good to the patient population.

OMER has this data definitive endpoint date, survival. Using the ultimate Primary Endpoint that can be compared to the establish Mortality Rate for HSC-TMA patients who fail existing treatment (which is ~90% mortality).

4. The FDA has requested the Omeros provide their data and a compilation of existing disorder etiology to which the progression of OMS-721 treated patients can be compared. The CEO, Dr. Gregory Demopulos, has indicated the company is compiling the OMS721 data and the general HSC-TMA survival data to submit to the FDA.

5. The FDA may be convinced by the existing data or require a larger sample from the patient population and then decide whether OMS721 clearly helps patients survive compared to currently standard treatment. OMER is going to show about 80% survival for a ~year for those treated with OMS721 and that about 90% of the population of patients who are not treated with the drug are dead earlier than those who are treated.

Rafael Duarte, M.D., Ph.D., F.R.C.P.(Lon), Associate Professor, Head of Hematopoietic Transplantation and Hemato-oncology Section, University Hospital Puerta de Hierro Majadahonda, Madrid, Spain, and Secretary of the European Society for Blood and Marrow Transplantation, quoted in the OMER press release about the Breakthrough Therapy Designation reward, explained why time is of the essence in getting OMS721 to these patients.

“Patients with HSCT-TMA who cannot undergo or do not respond to modification of immunosuppressive therapy are at very high risk of death from this complication. Currently, there is no approved treatment for HSCT-TMA, which remains one of the most pressing therapeutic needs in the field of HSCT. The impressive effect on survival and other results seen in OMS721-treated patients are quickly apparent following initiation of OMS721 therapy and can’t be explained by other factors. The HSCT community looks forward to the drug’s broad availability for our patients.”

6. If the FDA concludes OMS721 works and is a significant net benefit to prolong the lives of people who will almost surely die relatively quickly, the FDA will also review Omeros' proof of their ability to make, store, and deliver the drug safely.

7. If/when the FDA is satisfied the drug needs to be on the market to save lives and that OMER can safely provide the drug, the remaining issues are the instructions to physicians and the agreement with OMER for the design of the post-Marketing-Approval Phase IV trial.

8. If the FDA approves OMS721 for Marketing after Phase III has started, the Phase III trial may just become the Phase IV post-marketing trial.

CONCLUSIONS:

- The data collected so far indicate that OMS721 saves lives of HSC-TMA patients who do not respond to existing methods to stop them from dying.

- Even with significant therapeutic benefits for a number of life-threatening disorders, OMS721 has been shown, across multiple trials, to have negligible side effects, especially considering the consequences of no treatment.

- OMS721 research to treat HSC-TMA patients uses the ultimate endpoint, survival, and needs no surrogate endpoint to show that it works... or to speed up the trial to hasten approval... because the HSC-TMA patients most in need of treatment do not survive long without OMS721.

Therefore, my view is that there is NO NEED for Accelerated Approval or a Phase III, because there is NO SURROGATE ENDPOINT required. If/when the FDA is convinced that the data indicate OMS721 saves lives with little risk, they can approve the drug with or without an AA approval. I also note that there are no fixed application rules for AA and the FDA can review drug candidates whenever they want.

People with TMAs from a hematopoietic transplant (usually of bone marrow, peripheral blood, or umbilical cord blood), typically to treat cancer, are at significant risk of dying from their transplant treatment. OMS721 gives them a chance to survive that they now do not have, without OMS721.

There are no data on FDA procedures that allow us to predict if/when the FDA will act to provide potentially life-saving OMS721 treatment. Given that the risk to patients is low and the risk of dying without treatment is high, a compassionate FDA should approve it as soon as possible. To gain approval, Omeros needs to provide
- the treatment and disease information the FDA requested, now being compiled
- substantiation of the ability to manufacture and supply adequately labeled and safe drugs to the market

Whether and when the FDA will act is an unknown.