Alnylam Announces Positive Long-Term Data from ONPATTRO Trial
Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) announced data from its Global Open Label Extension study of ONPATTRO for treating polyneuropathy of hereditary ATTR (hATTR) amyloidosis in adults. This interim 24 months data evaluated the drug candidate’s long-term efficacy and safety in eligible patients who completed the Phase 2 OLE (N=25) and APOLLO Phase 3 (N=186) studies.
The APOLLO Phase 3 trial was a randomized, double-blind, placebo-controlled, global study. The primary endpoint of the study was the change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) relative to placebo at 18 months. Its secondary endpoints include the composite autonomic symptom score-31 (COMPASS-31), timed 10-meter walk (10-MWT) and Rasch-built Overall Disability Scale (R-ODS) among others. The trial also involved exploratory cardiac assessments such as echocardiography.
The APOLLO Phase 3 trial enrolled 225 hATTR amyloidosis patients with 39 genotypes and these patients were then randomized on 2:1 basis to be given patisiran and placebo respectively. The drug candidate was given at 0.3 mg/kg once every three weeks for 18 months. All the participants completing the APOLLO Phase 3 study were qualified to screen for the Global OLE study, where they had the opportunity of receiving ONPATTRO on continuous basis.
The reported data included 178 patients who had 24 months or greater of exposure as of the cutoff data of October 7, 2019. The study showed that the reduction in serum TTR levels in patients treated with the drug candidate was maintained with continued dosing in the Global OLE study. Patients on treatment for 42 months showed continued improvement in neuropathy impairment and quality of life relative to APOLLO study baseline. This factor was measured by negative changes in modified Neuropathy Impairment Score + 7 and Norfolk Quality of Life – Diabetic Neuropathy scores. Patients on treatment from the Phase 2 OLE population also showed an improvement in mNIS+7 score over the period of 48 months.
The long-term safety profile of the drug candidate was in line with that observed and previously reported in the APOLLO Phase 3 study and the Phase 2 OLE study. Eric Green, SVP and General Manager of the TTR Program said, “As of March 2020, thirteen patients who rolled onto the Global OLE study have received ONPATTRO for more than six years, the longest-running clinical experience with an RNAi therapeutic. In addition, the interim post-OLT data demonstrated robust TTR knockdown in this very high unmet need population and point to the breadth of patients that may benefit from treatment with ONPATTRO.”
The company also provided data for the patients which were in APOLLO placebo group but were treated with atisiran for 24 months in the OLE study. These patients demonstrated notable decline in neuropathy progression and their QOL also improved. However, during the APOLLO study, these patients had shown rapid progression while on placebo and did not show return to their baseline score later on.
Geron to Initiate Phase 3 Clinical Trial in Myelofibrosis
Geron Corporation (GERN) announced that it plans to start Phase 3 clinical trial for patients suffering from Myelofibrosis, who are refractory to treatment with a janus kinase inhibitor. The company provided details regarding the trial design, expected timelines and future data announcements. Geron took the step after its meeting with the FDA.
The upcoming trial will be an open label study and will be randomized 2:1. This controlled trial will seek to assess imetelstat, 9.4 mg/kg (administered by intravenous infusion every three weeks) in patients suffering from Intermediate-2 or High-risk MF. The trial is expected to have approximately 320 participants. John A. Scarlett, M.D., Chairman and Chief Executive Officer said, “We are very pleased to announce that following a productive meeting with the FDA, we plan to move forward with a randomized Phase 3 clinical trial in refractory Myelofibrosis. Our planned Phase 3 clinical trial in refractory MF will compare imetelstat to best available therapy that excludes JAK inhibitors and has overall survival as the primary endpoint.” The company intends to use the data for differentiating imetelstat from current therapies.
The participants are required to be refractory to a JAK inhibitor to be eligible for the trial. The criterion is defined as having an inadequate spleen response or symptom response after treatment with a JAK inhibitor for at least six months, including an optimal dose of a JAK inhibitor for at least two months. The control arm will received Best Available Therapy excluding JAK inhibitors.
The primary endpoint for the trial will be Overall Survival while planned key secondary endpoints will include spleen response, symptom response complete response and progression free survival, amongst others. Currently, the prospective Phase 3 clinical trails has been formulated with more than 85 percent power for detecting a 40 percent reduction in the risk of death for the patients treated with imetelstat.
Atara Bio Reports Encouraging Data from Phase 1 MS Trial
Atara Biotherapeutics (ATRA) stock jumped up as the company reported positive interim data from its Phase 1 dose escalation trial for ATA188. The drug candidate is an off the shelf allogeneic Epstein-Barr Virus (EBV) T-cell immunotherapy and seeks to treat patients suffering from progressive multiple sclerosis. The estimated primary completion date for the trial is in September 2022.
The data presented is a six months clinical results for the dose escalating cohorts of 1-4 and 12 months results for cohorts 1-3. The company will be presenting 12 months cohort 4 data during the second half of this year. The Part 1 of the study involved the participants receiving 2 cycles of the drug candidate and then proceed to 12 months follow up period after the last dosage. The Part 2 of the study involved randomizing the participants in 5:4 ratio for receiving the drug candidate at the RP2D or matching placebo.
The data showed that the drug candidate led to disease reversal in two of the total six patients included in the high dose cohort. The change was measured by a scale known as The Expanded Disability Status Scale or EDSS. It is a tool for measuring the extent of disability in multiple sclerosis patients and thereby carrying on monitoring of the changes. The scale ranges from 0 to 10 representing higher levels of disability.
Epstein-Barr Virus (EBV) is associated with a wide range of conditions such as hematologic malignancies, solid tumors and autoimmune conditions such as multiple sclerosis. T-Cells form a critical part of the human body’s immune system. These cells are believed to be capable of targeting EBV selectively and thus may be useful in treating these conditions. The drug candidate demonstrated the potential to target EBV-infected B-cells and plasma cells in the central nervous system.
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