Clinical Catch-Up: January 6-10, 2020

Clinical research

The first full business week of the new year began with plenty of clinical trial news. Here’s a look.

Pfizer and EMD Serono, the biopharmaceutical unit of Merck KGaA, Darmstadt, Germany, announced that their Phase III JAVELIN Bladder 100 trial hit its primary endpoint at a planned interim analysis. The primary endpoint was overall survival (OS). Bavencio is a checkpoint inhibitor of PD-L1.

The trial looked at patients with previously untreated locally advanced or metastatic urothelial carcinoma (UC) whose disease didn’t progress on induction chemotherapy. They were randomized to receive first-line maintenance therapy with Bavencio (avelumab) and best supportive care (BSC). Those receiving the drug lived significantly longer than patients who received BSC alone.

BridgeBio Pharma’s QED Therapeutics dosed first patients in its PROOF Phase III trial of oral infigratinib in adults for first-line treatment of advanced cholangiocarcinoma with FGFR2 gene fusions or translocations. They also announced the FDA had granted the drug Fast Track Designation and Orphan Drug Designation. Cholangiocarcinoma is a cancer of the bile ducts of the liver. The PROOF trial will enroll about 384 patients with first-line cholangiocarcinoma with FGFR2 fusions or translocations. The primary endpoint is progression-free survival compared to standard-of-care chemotherapy.

Merck & Co. released results from the Phase III KEYNOTE-604 trial of its checkpoint inhibitor Keytruda (pembrolizumab) with chemotherapy in extensive stage small cell lung cancer (ES-SCLC). The study met one of its dual primary endpoints, progression-free survival (PFS), but missed the other endpoint, overall survival (OS). KEYNOTE-604 was a randomized, double-blind, placebo-controlled Phase III study of Keytruda in combination with chemotherapy, in this case, etoposide plus cisplatin or carboplatin, compared to chemotherapy alone in patients with newly diagnosed ES-SCLC. The dual primary endpoints were OS and PFS. Secondary endpoints were objective response rate (ORR), duration of response (DOR), safety and quality of life. It enrolled 453 patients.

Apellis Pharmaceuticals announced that its pegcetacoplan beat out Alexion Pharmaceuticals Soliris in its Phase III PEGASUS study in adults with paroxysmal nocturnal hemoglobinuria (PNH). PNH is a rare, chronic, life-threatening disease of the blood linked to abnormally low hemoglobin levels caused by the destruction of red blood cells. The PEGASUS study evaluated 80 adults with PNH, comparing pegcetacoplan to Alexion’s Soliris (eculizumab). The primary endpoint was the superiority of pegcetacoplan to eculizumab, which it met, with a statistically significant improvement in adjusted means of 3.8 g/dL of hemoglobin at week 16. Pegcetacoplan also showed promise in key secondary endpoints, such as non-inferiority on transfusion avoidance and absolute reticulocyte count.

Vitalis Pharmaceuticals announced results of Type C meeting with the FDA for VTS-72.VTS-72 is being developed for treatment of patients with relapsing/remitting multiple sclerosis (RRMS) who experience the Fumarate Flush, a common side effect of fumaric acid. It is a proprietary combination of fumarate and VTS-Aspirin. Based on the results of the meeting, Vitalis plans to pursue an initial approval of VTS-72 and initiate the necessary dose ranging and bioequivalence studies soon, followed by a Phase III trial.

The Immune Tolerance Network (ITN) opened the BEAT-MS clinical trial for enrollment. The trial will evaluate high dose immunosuppression followed by AHSCT, a type of transplant using the patient’s own immune stem cells.

Advaxis announced the FDA had cleared its IND for the launch of a Phase I trial of ADXS-504. The compound is the company’s ADXS-HOT candidate for prostate cancer. ADXS-HOT is its off-the-shelf neoantigen clinical program targeting hotspot mutations that include over 10 cancer-type specific drug constructs.

CureVac AG announced positive data from an interim analysis of safety and immunogenicity in its Phase I trial of CV7202. CV7202 is a novel prophylactic mRNA-based rabies vaccine. In the trial, all patients who received two doses of the lowest dose of the vaccine showed a strong adaptive immune response with protective virus-neutralizing antibody titer levels.

Sequana Medical NV dosed the first patient in its RED DESERT trial of alfapump DSR for diuretic-resistant heart failure patients. The prospective, single-arm, repeated dose trial is expected to include up to 10 heart failure patients who are on high-dose diuretics. The trials will be in Belgium and Georgia.

TLC dosed the first group of patients in Part 2 of its Phase II trial of TLC590 in patients after bunionectomy surgery. TLC590 is a non-opioid, proprietary BioSeizer sustained release formulation of ropivacaine. It is being tested for managing postsurgical pain for three days or more with a single dose. Phase I completed last year. All three doses of TLC590 were well tolerated with a safety profile similar to ropivacaine.

Galera Therapeutics dosed the first patient in a Phase IIa trial of avasopasem manganese to decrease the incidence of radiation-induced esophagitis in patients with lung cancer. Avasopasem manganese is a highly selective small molecule superoxide dismutase (SOD) mimetic. Its initial development is to reduce radiation-induced severe oral mucositis (SOM). The trial will look at about 60 adults with pathologically confirmed unresectable Stage 3A/3B or post-operative Stage 2B non-small cell (NSCLC) or limited-stage small cell (SCLC) lung cancers.

Nanobiotix plans to launch a late-stage head and neck cancer registration trial. It is working with The University of Texas MD Anderson Cancer Center in the U.S. and PharmaEngine in Asia to accelerate plans for advancing the Nanobiotix immuno-oncology program and evaluating NBTXR3 in other indications, such as lung, pancreatic, esophageal, HCC, prostate, and rectal cancers. NBTXR3 is a first-in-class radioenhancer designed to destroy tumors without increasing damage to surrounding healthy tissues.

SCYNEXIS announced positive results from the second interim analysis of its Phase III FURI study of oral ibrexafungerp as a salvage treatment in difficult-to-treat mucocutaneous and invasive fungal infections that are refractory to or intolerant of current standards of care or that require a non-azole oral step-down therapy for azole-resistant Candida species. Ibrexafungerp is the first representative of a novel antifungal family, the “fungerps,” which are being developed for oral and IV treatment of multiple serious fungal infections.

VBL Therapeutics published clinical data from its Phase II and Phase III trials of VB-11 (ofranergene obadenovec) in recurrent glioblastoma (rGBM). They are published separately in the journal Neuro-Oncology. In the Phase II study, patients with rGBM were primed with VB-111 monotherapy that was continued after progression with the addition of Avastin showed significant survival and PFS advantage compared to the patients with limited exposure to VB-111. In the Phase III trial, concomitant administration of VB-111 without priming and Avastin added to bevacizumab monotherapy did not improve OS and PFS in rGBM. The contradictory outcomes, they speculate, are related to the lack of VB-111 priming.

Tyme Technologies dosed the first patient in Part 2 of the TYME-88-Panc pivotal trial in metastatic pancreatic cancer. SM-88 (racemetyrosine) is being evaluated for third-line treatment of metastatic pancreatic cancer. CMBTs are investigational compounds believed to disrupt cancer cells’ protein synthesis. SM-88 has shown encouraging tumor responses across 15 different types of cancers, including pancreatic, prostate, sarcoma, breast, lung, and lymphoma.

Locus Biosciences opened enrollment for a Phase IB trial of LBP-EC01, a CRISPR Cas3-enhanced bacteriophage that will target E. coli causing urinary tract infections. LBP-EC01 is a bacteriophage cocktail engineered with a CRISPR-Cas3 construct targeting the genome of E. coli. It works via a unique dual mechanism of action that uses both the natural lytic properties of the bacteriophage with the DNA-targeting activity of CRISPR-Cas3.

Regeneron Pharmaceuticals reported its Phase II LUMINA-1 trial of garetosmab in fibrodysplasia ossificans progressive (FOP) showed almost a 90% decrease in the formation of new lesions. FOP is an ultra-rare genetic disorder with no approved treatments. It leads to abnormal bone formation that can cause skeletal deformities, progressive loss of mobility and premature death. Garetosmab is a monoclonal antibody that neutralizes the Activin A protein.

DBV Technologies released positive long-term data from its Phase III PEPITES trial looking at Viaskin Peanut in peanut-allergic children aged 4 to 11 years. After three years, 85.9% of children in the trial, 107 out of 141, increased their eliciting dose (ED) from baseline. And about 51.8% hit an ED of at least 1,000 mg peanut protein by the third year.

Zai Lab and NovoCure enrolled the first patient in a Phase II trial evaluating Tumor Treating Fields in combination with chemotherapy as first-line treatment in gastric adenocarcinoma. Tumor Treating Fields is already approved for glioblastoma and malignant pleural mesothelioma in the U.S. It is a cancer therapy that utilizes electric fields tuned to specific frequencies to disrupt cell division, inhibit tumor growth and possibly kill cancer cells.

Acepodia announced the FDA has cleared its IND to initiate a Phase I trial of its natural killer cell therapy and lead candidate ACE1702 in HER2-expressing solid tumors. ACE1702 was developed from the company’s ACC platform. It targets human HER2-expressing solid tumors using anti-HER2 antibody conjugated oNK cells.

Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals, initiated the CARDIO-TTRansform Phase III trial of AKCEA-TTR-LRX in transthyretin-mediated amyloid cardiomyopathy. AKCEA-TTR-LRX is an antisense drug developed using Ionis’ Ligand Conjugated Antisense (LICA) technology platform designed to inhibit production of TTR. The trial is a global, double-blind, randomized, placebo-controlled Phase III cardiovascular outcome study comparing the therapy to placebo.

Elysium Health initiated a clinical trial at Duke Clinical Research Institute to study correlations between biological age and circulating NAD+ levels in healthy adults. Biological age will be determined using Elysium Health’s next-generation epigenetic platform, Algorithmic Platform for Epigenetic Examination (APEX). NAD+ is an essential coenzyme involved in numerous metabolic processes. In its reduced form, NADH, it is required for mitochondrial metabolism and energy production.

Seelos Therapeutics announced interim data from its Phase I study of Intranasal Racemic Ketamine (SLS-002). The data showed that 60 mg of SLS-002, given as a monotherapy and in combination with an oral antidepressant, was generally safe and well-tolerated. All adverse events except one were mild or moderate and transient in nature. The trial is a single-center, open-label study of 42 healthy volunteers studied over 14 days.

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