dm+d

Unassigned

New Medicines

Information

New molecular entity
Omeros
Omeros

Development and Regulatory status

None
Phase III Clinical Trials
Not recommended for approval (Negative opinion)
Yes
Yes
Oct 21The FDA have issued a complete response letter. According to Omeros, the FDA expressed difficulty in estimating the treatment effect of narsoplimab and additional information is needed to support regulatory approval. Omeros are confident in its efficacy and safety data and are working with the FDA on a clinical development plan [15].
Oct 21As part of the on-going review of the BLA the FDA has identified deficiencies that preclude discussion of labeling and post-marketing requirements/commitments at this time. FDA stated that the notification does not reflect a final decision on the information under review. The FDA expressed its intention to work with Omeros to resolve any issues as expeditiously as possible, but the company does not currently expect any such resolution to occur by the October 17, 2021 target action date under the Prescription Drug User Fee Act (PDUFA) [14]
Mar 21Omeros annual report indicates EU filing by end of 2021 [13].
Nov 20Omeros report rolling submission of BLA to FDA for narsoplimab for treatment of HSCT-TMA is completed [12].
Dec 19Omeros report plans to publish data from its pivotal PIII (NCT03205995) trial at the international congresses in the first part of 2020. Data from this trial will support the MA for HSCT-TMA in Europe [9].
Nov 19Omeros reported the initiation of its rolling BLA [9].
Oct 19Narsoplimab receives Positive Opinion from European Medicines Agency for a Paediatric Investigation Plan to evaluate the safety and effectiveness of the drug for HSCT-TMA in patients from 1 month through 17 years of age [8].
Sep 19FDA agrees with Omeros a schedule for the rolling review of a Biological License Application (BLA) for narsoplimab in HSCT-TMA. Omeros will submit first sections of the BLA in the first half of Q4 19. The first sections of the BLA will include the nonclinical and clinical pharmacology data [7].
Apr 19Omeros receives positive feedback from the EMA Pediatric Development Committee on its Pediatric Investigational Plan, for use of narsoplimab for the treatment of HSCT-TMA. They also intend to meet the rapporteurs assigned to their application in Q2 19 [7].
Oct 18US FDA grants orphan drug status for narsoplimab for treatment of HSCT-TMA [5].
Aug 18Granted orphan drug status in EU for treatment of HCT-TMA. Omeros is in discussion the US FDA and the European Medicines Agency regarding the most expeditious path for approval of OMS 721 in HCT-TMA, & is also seeking the PRIME status [5].
Apr 18US FDA grants breakthrough therapy designation to OMS 721 for treatment of patients with high-risk HSCT-TMA, specifically in patients who have persistent TMA despite modification of immunosuppressive therapy. The designation was based on positive PII clinical trial data evaluating OMS 721 in patients with high-risk HSCT-TMA [5].

Category

Human monoclonal antibody that targets mannan-binding lectin-associated serine protease-2 (MASP-2).
TMAs are a family of rare, debilitating and life-threatening disorders characterised by excessive thrombi in the microcirculation of organs, most commonly kidney and brain [1].
Haematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT-TMA)
Intravenous

Trial or other data

Nov 20Omeros announce final data from pivotal trial of narsoplimab in HSCT-TMA. In trial (n=28) narsoplimab IV once weekly for 8 weeks showed a 61% (95% CI: 40.6% to 78.5%) complete response rate (CRR) in the full analysis set (FAS; patient receiving at least one dose of narsoplimab; p<0.0001 compared to 15% efficacy threshold agreed with FDA) 74% (95% CI: 51.6% to 89.8%) CRR in the per-protocol (PP) population (patients receiving the protocol-specified narsoplimab treatment for at least 4 weeks; p<0.0001 compared to the 15% threshold). Adverse events included fever, diarrhoea, vomiting, nausea and neutropenia). Six deaths occurred in the study and were attributed to causes common in HSCT [11].
Jul 19Omeros has reached an agreement with the FDA on the full set of criteria for the primary endpoint for narsoplimab pivotal trial. As per the agreement, the response-based primary endpoint for HSCT-TMA must exhibit both a beneficial effect on the underlying HSCT-TMA disease process and improvement in patients’ clinical status. The endpoint includes laboratory measures and markers of organ function as well as platelet and red blood cell transfusion burden [7].
Feb 18Omeros reports that PIII study is in progress for OMS 721 in HCT-TMA [5].
Feb 18Omeros announces new results from the ongoing PII study (NCT02222545). The data demonstrate an increase in median overall survival in HCT-TMA patients treated with OMS721 compared to a matched historical control (347 days vs. 21 days, respectively, by Kaplan-Meier analysis; p < 0.0001 by log-rank test). Historical control data are typically used for comparison when it is impractical or unethical to include a placebo arm in a clinical trial. In addition to and consistent with the survival data reported today, updated assessments of platelet count, lactate dehydrogenase (LDH) and haptoglobin – all markers of TMA activity – continue to demonstrate clinically meaningful and statistically significant improvements in the HCT-TMA patients treated with OMS721. A total of 19 HCT-TMA patients have been treated to date with OMS721, 18 in the ongoing study and one patient under a compassionate use protocol. An historical control that best matched the OMS721-treated population was identified from the literature. The literature reference selection criteria were those studies that specified: (1) individual patient data (required for analysis), (2) adult and/or adolescent populations, (3) allogeneic stem cell transplant recipients only, and (4) no or partial response to immunosuppressive regimen modification. Overall median survival demonstrated greater than 16-fold improvement in survival in the OMS721-treated group (p < 0.0001). Markers of TMA activity in study participants, specifically mean platelet count, mean LDH, and mean haptoglobin, continue to demonstrate statistically and clinically significant improvements following OMS721 treatment. At the end of protocol-allowed treatment, the mean platelet count (normal range: 150,000 – 400,000 x 106/mL) increased from 18,100 x 106/mL at baseline to 52,300 x 106/mL (p = 0.017). The mean LDH (normal range: 125-220 U/L) decreased from 591 U/L at baseline to 250 U/L (p < 0.001). The mean haptoglobin (normal range: 14-268 mg/dL) increased from 8 mg/dL at baseline to 141 mg/dL (p = 0.003). Mean creatinine remained stable at approximately 120 µmol/L (normal range: 63-104 µmol/L) but a majority of patients had co-existing conditions for which they were receiving nephrotoxic medications. Other serious co-existing conditions included graft versus host disease (GvHD), cytomegalovirus and human herpes virus 6 infections, prior sepsis, diffuse alveolar hemorrhage, and residual underlying malignancies [6].
Jan 18Omeros announces its intention to amend the ongoing PII protocol, following discussion with the US FDA and/or the EMA, to transit into a PIII/pivotal trial [5].
Aug 15PII data reported (NCT02222545). Three patients were treated in the second or mid-dose cohort, two of whom have aHUS and one with TTP. Both patients with aHUS were on renal dialysis prior to and at the time of study enrollment. Based on the positive data from the mid-dose cohort, the high-dose cohort was initiated and an aHUS patient has already completed the study treatment period. No patient with HSCT-related TMA has yet completed dosing with OMS721. In the trial, platelet counts in all three aHUS patients in the mid- and high-dose cohorts (two in the mid-dose and one in the high-dose cohort) were normal after the treatment period, with a statistically significant mean increase from baseline of approximately 68,000 platelets/mL (p=0.0055). In the mid-dose cohort, the two patients with plasma therapy-resistant aHUS demonstrated a 47% increase in mean platelet count, resulting in both patients having counts in the normal range, an 86% decrease in mean schistocyte count, with schistocytes disappearing in one patient, a 71% increase in mean haptoglobin with both patients reaching the normal range during treatment, one slipping slightly below normal at one week following the last dose, and a 5% decrease in the mean levels of LDH, with levels in both patients remaining slightly elevated above normal range [1].
Aug 15As in Alexion´s clinical trials supporting US and EU approval of Soliris for treatment of aHUS, the OMS-721 PII trial has no placebo arm. Soliris trials also used change from baseline in platelet count as a primary endpoint [1].
Aug 15Omeros announces data from a small, three-pronged PII trial. Patients getting the middle dosage of OMS-721 showed an increase in platelet counts, lower dangerous blood cell fragmentation and a boost in the blood protein haptoglobin. Omeros is still enrolling the high-dose arm of the study, but the one patient who has completed four-week OMS-721 therapy showed signs consistent with both the middle group and the low-dose cohort disclosed earlier in 2015. No serious drug-related adverse events were reported [1].
Aug 14Two-stage dose-escalation PII trial to assess the efficacy, safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of OMS 721 in adult patients with TMAs, including atypical haemolytic uraemic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP) and haematopoietic stem cell transplant (HSCT)-related TMAs starts (NCT02222545). The randomised, open-label trial is designed to enrol approximately 29 patients in the US, Belgium, Poland and Lithuania. The pre-specified primary endpoint is change from baseline in platelet count [5].

Atypical haemolytic uraemic syndrome (aHUS) in patients aged ≥12 years

Information

Licence extension / variation
Omeros
Omeros

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

Human monoclonal antibody that targets mannan-binding lectin-associated serine protease-2 (MASP-2).
HUS is a rare disorder with an annual incidence of 6.1 cases per 100,000 children aged under 5 years (compared with an overall incidence of 1 to 2 cases per 100,000). About 10% of HUS cases are atypical and are not caused by Shiga toxin-producing bacteria or streptococci. Patients without evidence of underlying infection should be fully investigated, in particular looking for complement gene mutations [1].
Atypical haemolytic uraemic syndrome (aHUS) in patients aged ≥12 years
Intravenous and
Subcutaneous injection

Immunoglobulin A (IgA) nephropathy (Berger disease)

Information

Licence extension / variation
Omeros
Omeros

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

Human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a key component in the lectin pathway of complement activation.
IgA nephropathy is the most common form of idiopathic glomerulonephritis leading to chronic kidney disease (CKD) in developed countries. In most cases it follows a benign course, however between 30% to 40% of patients will progress to end-stage renal disease within 20 years [2].
Immunoglobulin A (IgA) nephropathy (Berger disease)
Subcutaneous injection