Out of the starting gate
November 2017
by Jeffrey Bouley  |  Email the author


To kick off our look at early-stage trials and beginnings of new phases, Oct. 19 brought news from Esanex Inc., a clinical-stage company developing heat shock protein (Hsp) inhibitors for the treatment of cancer, announcing that the first patient had been dosed in an open-label study of SNX-5422 added to ibrutinib in chronic lymphocytic leukemia (CLL) subjects with residual disease.
“Resistance to ibrutinib is a serious concern in CLL,” says Dr. Jennifer A. Woyach, of Ohio State University. “SNX-5422 is designed to attack cancer cells by a different, complementary mechanism, making their escape from cell death much harder. There is a critical need to develop drugs and drug combinations for the patients suffering from this life-threatening disease.”
The study is designed to investigate the safety of combining SNX-5422 and ibrutinib and provide information on whether the addition of SNX-5422 to an established dose of ibrutinib will provide clinical benefit in subjects who have stable, residual disease on ibrutinib alone. In each cycle, subjects will receive SNX 5422 (56 mg/m2) in the morning once every other day for 21 days (11 doses), followed by a seven day period without SNX-5422 treatment. Subjects will continue to receive daily oral ibrutinib at their established dose level in the afternoon.
“The initiation of this clinical trial marks a major milestone for our company,” said Dr. Steve Hall, president and CEO of Esanex. “The new mechanistic understanding of SNX-5422 that Esanex has uncovered, which differentiates our compound from other Hsp90 inhibitors, has enabled us to rationally approach monotherapy and select combination therapies for distinct indications. We believe we are only beginning to see the potential of SNX-5422 and Hsp90 inhibition as a treatment for cancer and possibly other diseases.”
SNX-5422 is a chemically unique, orally active Hsp90 inhibitor that has provided durable clinical responses in open-label trials in non-small cell lung cancer and neuroendocrine tumors before the company began to test the potential of SNX-5422 in hematologic cancers in humans, beginning with CLL.

ARGX-113 vs. autoimmune disease
BREDA, the Netherlands & GHENT, Belgium—In late September, argenx, a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, announced the initiation of a Phase 2 proof-of-concept clinical trial of ARGX-113 in pemphigus vulgaris (PV) patients.
“PV is a chronic, severe and potentially life-threatening orphan autoimmune disease of the skin for which limited treatment options exist. Disease severity is directly correlated to pathogenic antibodies of the immunoglobulin G (IgG) type targeting desmoglein-1 and -3 in the skin, leading to painful blister formation and skin damage,” commented Nicolas Leupin, CEO of argenx. “Current treatment options are limited to high-dose steroids and chronic immunosuppression. We are thrilled about the therapeutic potential of ARGX-113 in PV, based on its mode of action of clearing IgGs. PV represents a clean and rapid proof-of-concept indication and, we believe, is therefore our ideal beachhead into the field of severe autoimmune blistering diseases of the skin.”
The open-label, non-controlled trial will enroll up to 12 patients with mild to moderate PV who are either newly diagnosed or relapsing. The primary endpoints of the trial are safety and tolerability, and secondary endpoints include efficacy and an assessment of pharmacokinetics and pharmacodynamic markers. ARGX-113 is currently being tested in two additional Phase 2 clinical trials in myasthenia gravis and immune thrombocytopenia, top-line data for which are expected in the first quarter and second half of 2018, respectively.

Gene therapy for wet AMD
ROCKVILLE, Md.—REGENXBIO Inc., a clinical-stage biotechnology company working on the curative potential of gene therapy based on its proprietary NAV technology platform, recently announced that the first cohort of six patients has been dosed in a Phase 1 clinical trial evaluating RGX-314 for patients with wet age-related macular degeneration (wet AMD).
“All six study sites are now active to support enrollment in the next dose cohort that is projected to start after review by the Data Safety Monitoring Board this month,” said Dr. Stephen Yoo, chief medical officer of REGENXBIO. “Our goal with this trial is to confirm prior observations in preclinical animal models that treatment with RGX-314 can deliver rapid and sustained therapeutic effects to provide long-lasting treatment for patients with wet AMD.”
Six leading retinal surgery centers across the United States are participating in the Phase 1 trial of RGX-314. This multicenter, open-label, multiple-cohort, dose-escalation clinical trial is designed to assess the safety and tolerability of RGX-314 as a one-time therapy for patients with previously treated wet AMD. The company plans to share an interim trial update by the end of 2017.

Going after psoriatic arthritis
PLANEGG, Germany—MorphoSys AG announced recently that its licensee Janssen Research & Development has initiated two Phase 3 clinical trials to evaluate the efficacy and safety of Tremfya (guselkumab) in the treatment of patients with psoriatic arthritis (PsA), a chronic, immune-mediated inflammatory disease affecting both the joints and the skin. Tremfya is a fully human anti-IL-23 monoclonal antibody developed by Janssen, and was generated utilizing MorphoSys's proprietary HuCAL antibody technology.
MorphoSys will receive a milestone payment from Janssen in connection with the start of Phase 3 development in PsA. Specific financial details were not disclosed.
“We are very pleased that our licensee Janssen has started pivotal Phase 3 development with Tremfya in psoriatic arthritis. If successful, this could result in a further expansion of the therapeutic range of the compound,” said Dr. Markus Enzelberger, interim chief scientific officer of MorphoSys. “Through Janssen's innovative development of Tremfya leading to U.S. FDA approval, it recently became the first therapeutic antibody based on MorphoSys's technology platform that has been made available to patients in the U.S.”

Immunotherapy for gastric cancer
TEL AVIV, Israel—BioLineRx Ltd., a clinical-stage biopharmaceutical company focused on oncology and immunology, announced in September that Genentech, a member of the Roche Group, has commenced a Phase 1b/2 study for the treatment of gastric cancer with BL-8040 in combination with atezolizumab (Tecentriq), Genentech’s anti-PDL1 cancer immunotherapy agent.
Up to 40 patients are planned to be enrolled in this multicenter, randomized, controlled, open-label study to evaluate the clinical response, safety and tolerability—as well as multiple pharmacodynamic parameters—of BL-8040 in combination with atezolizumab. Initially, patients will receive BL-8040 injections as priming monotherapy, after which they will receive both BL-8040 and atezolizumab, and continue with multiple treatment cycles for up to two years or until disease progression, clinical deterioration or unacceptable toxicity.
The clinical study collaboration between BioLineRx and Genentech is part of MORPHEUS, Roche's novel cancer immunotherapy development platform. MORPHEUS is a Phase 1b/2 adaptive platform to develop combinations of cancer immunotherapies more rapidly and efficiently.
“This is the third trial to commence under our collaboration with Genentech for the combination of our CXCR4 inhibitor lead oncology platform and their anti-PDL1 inhibitor, following initiation of a pancreatic cancer study in July and initiation of an AML study in September,” noted Philip Serlin, CEO of BioLineRx. “We are therefore hopeful that combining atezolizumab with BL-8040 can lead to a significant advancement in the treatment of gastric cancer, and of other solid tumors that are difficult to treat. BL-8040 has shown to induce robust mobilization of immune cells, improve the infiltration of T cells into solid tumors and affect the immunosuppressive tumor micro-environment. We look forward to the results of this trial and the initiation of an additional combination study under this collaboration, planned for later this year."

First patients randomized in acromegaly trial
WALTHAM, Mass.—Chiasma Inc., a clinical-stage biopharmaceutical company focused on improving the lives of patients with rare and serious chronic diseases, in late September provided an update on both of its international Phase 3 clinical trials of its octreotide capsules product candidate, conditionally trade-named Mycapssa, for the maintenance therapy of adult patients with acromegaly.
The company announced the randomization of the first patient in its new Phase 3 trial, referred to as CHIASMA OPTIMAL, meeting its previous guidance that enrollment in the study would begin during the second half of 2017. The CHIASMA OPTIMAL study is being conducted under a Special Protocol Assessment with the Division of Metabolism and Endocrinology Products of the U.S. Food and Drug Administration (FDA).
Chiasma also announced that it recently surpassed 50 percent patients randomized in its international Phase 3 clinical trial, referred to as MPOWERED. It is a global, randomized, open-label and active-controlled, 15-month trial.
“This is an important day for Chiasma, as we achieved two significant milestones toward advancing octreotide capsules as a maintenance treatment for adult acromegaly patients,” said Mark Fitzpatrick, president and CEO of Chiasma. “Beginning enrollment in our CHIASMA OPTIMAL Phase 3 study is an important step toward our goal of resubmitting a New Drug Application with the FDA. We also are encouraged by our progress in enrolling patients in MPOWERED, Chiasma’s international Phase 3 study of octreotide capsules, to potentially support regulatory approval in Europe. We strongly believe in Mycapssa as a potential new treatment option for adult patients with acromegaly, and we look forward to continuing this important mission.”
Octreotide capsules are an investigational new oral drug proposed for the maintenance therapy of adult patients with acromegaly. Acromegaly is most commonly caused by a benign tumor of the pituitary gland that produces excess growth hormone, ultimately leading to significant health problems and early death if untreated. The current standard of care is somatostatin analog injections.
Code: E111719

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