Clinical Catch-up from Last Week: May 13-17
Biopharma companies never sit still. Almost every week they release results from ongoing clinical trials. Here’s a roundup of some of the top clinical trial news from the previous week.
Switzerland-based Polyphor temporarily halted enrollment for two Phase III clinical trials of its pneumonia treatment due to safety concerns. The two studies are PRISM-MDR and PRISM-UDR, evaluating murepavadin in patients with nosocomial pneumonia. Enrollment was halted because of “higher than expected acute kidney injury incidences” in the murepavadin arm of the PRISM-MDR trial. They were observed in 56% of patients treated in the study, much higher than the expected 25-40%. Murepavadin is a pathogen-specific antibiotic whose novel mechanism of action involves binding to an outer membrane protein of Pseudomonas aeruginosa.
The trial met its primary endpoint and six key secondary endpoints. For the primary endpoint, 73.4% of patients receiving once-daily doses of relugolix hit the responder criteria compared to 18.9% of women who received placebo. The response was defined as menstrual blood loss volume of less than 80 mL and a 50% or greater decrease from baseline in menstrual blood loss volume during the last 35 days of the 24-week treatment. On average, women receiving the relugolix combination therapy had an 84.3% reduction in menstrual blood loss from baseline, which was a key secondary endpoint.
Patients receiving the drug also maintained bone mineral density to levels comparable to those on placebo over 24 weeks. The therapy was generally well tolerated.
In its first-quarter financial report, Solid Biosciences updated on its Phase I/II IGNITE DMD clinical trial. The progress was marred by adverse events. One patient was dosed with 2E14 vg/kg of SGT-001 and another patient was added to the control group. Not long after dosing, however, the patient in the treatment group was diagnosed with a gastrointestinal infection. It was classified as a serious adverse event but was not believed to be related to the study drug. The patient also showed a transient decline in platelet count that was believed to be a non-serious adverse event related to the drug.
The events have fully resolved.
Zealand Pharma, based in Denmark, reported successful results in its Phase III trial of dasiglucagon for severe hypoglycemia in diabetes. The drug is a potential first-in-class soluble glucagon analog. In the trial, a single dose of dasiglucagon administered with the HypoPal rescue pen quickly increased blood glucose levels in patients with Type 1 diabetes after insulin-induced hypoglycemia (low blood sugar). The median time to blood glucose recovery was 10 minutes for dasiglucagon, superior to placebo, which had a median of 35 minutes.
Pfizer announced that its abrocitinib had positive top-line results in its Phase III trial in severe atopic dermatitis (AD). The trial, B7451012, evaluated abrocitinib as a monotherapy for 12 weeks. The top-line data indicated that by week 12 the proportion of patients who hit each co-primary efficacy endpoint and each key secondary endpoint with either dose, 100 mg or 200 mg, were statistically significantly higher than placebo.
The co-primary endpoints were the percentage of patients who hit an Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin and greater than or equal to 2-point improvement. The second co-primary endpoint was proportion of patients who hit at least a 75% or greater change from baseline in their Eczema Area and Severity Index (EASI) score.
Paris-based GenSight Biologics reported the first set of data from Week 96 of its REVERSE Phase III clinical trial in 11778-ND4 Leber Hereditary Optic Neuropathy (LHON). The trial evaluated the safety and efficacy of the company’s single intravitreal injection of GS010, a gene therapy, in 37 patients with LHON. The patients all had reported vision loss due to the disease between 6 and 12 months prior to treatment. Week 96 is the last scheduled readout for the study. It is also the time when the data was unmasked, providing the researchers with access to individual patient profiles.
LHON is a rare maternally-inherited mitochondrial genetic disease. It is marked by the degeneration of retinal ganglion cells. This results in irreversible vision loss that can lead to legal blindness. It primarily affects adolescents and young adults. It is associated with sudden loss of central vision in the first eye, with the other eye becoming sequentially impaired. About 97% of patients have bilateral involvement in less than a year after initial vision loss, and in 25%, vision loss in both eyes happens at the same time. In the U.S. and Europe, it is estimated that LHON affects 1,400 to 1,500 new patients every year.
ImmunoGen, based in Waltham, Mass., announced that the U.S. Food and Drug Administration (FDA) recommended it run a new Phase III clinical trial of mirvetuximab soravtansine in high folate receptor (FRα)-positive, platinum-resistant ovarian cancer.
FORWARD I is a Phase III clinical trial of 366 patients. They were randomized 2:1 to receive either mirvetuximab soravtansine or the doctor’s pick of single-agent chemotherapy (pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel). Eligible patients were diagnosed with platinum-resistant ovarian cancer that expressed medium or high levels of FRα and had received treatment up to three other times. The primary endpoint was progression free survival (PFS).
Mirvetuximab soravtansine is a humanized FRα-binding antibody that targets the antibody-drug conjugate (ADC) specifically to FRα-expressing cancer cells with a chemotherapy agent, DM4.
On March 1, ImmunoGen announced that the drug didn’t meet its primary endpoint in the FORWARD I trial. In the overall study population, confirmed overall response rate (ORR) was higher for the drug than chemotherapy alone, 22% to 12%, respectively, but without a significant difference in the primary endpoint of PFS. PFS was longer in patients receiving the ADC compared to chemotherapy alone in a subgroup with high FRα.
Agios Pharmaceuticals, headquartered in Cambridge, Mass., announced that its Tibsovo (ivosidenib) hit its primary endpoint in the Phase III ClarIDHy trial in patients with cholangiocarcinoma with an isocitrate dehydrogenase 1 (IDH1) mutation. Cholangiocarcinoma is a family of cancers that originate in the bile ducts.
The ClarIDHy trial was a global, randomized Phase III trial in previously treated IDH1 mutant cholangiocarcinoma patients whose disease had progressed after one or two systemic therapies. The trial involved 185 patients who were randomized 2:1 to receive either Tibsovo 500 mg once a day or a placebo with crossover to Tibsovo permitted at the time of documented radiographic progression per RECIST 1.1. The primary endpoint was progression-free survival (PFS) by independent radiology review. The drug met the primary endpoint.
MacroGenics announced positive data from its Phase III SOPHIA clinical trial of margetuximab in breast cancer. The trial evaluated margetuximab in patients with HER2-positive metastastic breast cancer who had already been treated with anti-HER2-targeted therapies. The drug is an immune-enhancing monoclonal antibody developed with MacroGenics’ proprietary Fc Optimization technology platform.
The trial met its first sequential primary endpoint, which was progression-free survival (PFS). Patients receiving margetuximab and chemotherapy had a median PFS of 5.8 months compared to patients receiving trastuzumab (Genentech’s Herceptin) and chemotherapy, who had a median of 4.9 months PFS.
In a pre-specified subpopulation in the study, patients carrying the CD16A 158F allele, which made up about 85% of the study, PFS was extended by 1.8 months in those receiving margetuximab compared to the trastuzumab arm. The objective response rate (ORR), which was a secondary endpoint, was 22% in the margetuximab arm and 16% in the trastuzumab arm.
AbbVie announced that it has halted its Phase III INTELLANCE-1 clinical trial of depatuxizumab mafodotin (Depatux-M) in patients with newly diagnosed glioblastoma (GBM) whose tumors have epidermal growth factor receptor (EGFR) amplification. An Independent Data Monitoring Committee (IDMC) recommended the trial be stopped because of lack of survival benefit for patients receiving the drug compared to placebo.
The trial compared the efficacy and safety of Depatux-M compared to placebo when given with concurrent radiation and temozolomide and with adjuvant temozolomide in patients with newly diagnosed EGFR-amplified GBM. The primary endpoint was overall survival (OS). The interim analysis was based on data from 639 patients.
Ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, Puma Biotechnology presented a meeting abstract. In it, the company’s Nerlynx (neratinib) in combination with Roche’s chemotherapy drug Xeloda (capecitabine) was compared to Novartis’ Tykerb (lapatinib) and Xeloda in breast cancer. The Nerlynx-Xeloda combination showed a treatment advantage.
The NALA clinical trial is a multinational, randomized, open-label, Phase III trial in patients with stage IV HER2+ metastatic breast cancer who had received two or more previous HER2-directed treatments. Patients were randomized 1:1 to receive Nerlynx and Xeloda or Tykerb and Xeloda. Co-primary endpoints were progression-free survival (PFS) and overall survival (OS).
The trial evaluated 621 patients. PFS for the Nerlynx-Xeloda cohort at 6 and 12 months were 47% and 38%, respectively. For the Tykerb-Xeloda cohort, the PFS at 6 and 12 months were 29% and 15%, respectively. In addition, overall survival at the same time points was higher for the Nerlynx-Xeloda group, 33% compared to 27% for the Tykerb-Xeloda group, but that wasn’t statistically significant.