Head to toe: Treatment approvals throughout the industry

A quick review of some recent treatment approvals, clinical studies and general news in curing diseases, affecting patients from top to bottom.

Head and neck above the rest

A late clinical-stage nanomedicine company, Nanobiotix, is extending its head and neck cancer programme with its lead product NBTXR3.

Head and neck cancer is an aggressive form of the disease and although highly curable if detected early, more advanced forms may require surgery in combination with chemotherapy and radiotherapy. However, surgical intervention can lead to severely debilitating side effects as a result of the area involved, such as swallowing or breathing issues post-op.

NBTXR3 is an aqueous suspension of specially coated nanoparticles that has been designed to enhance radiotherapy energy in tumour tissue. Based on the value of Phase I/II clinical data, being presented in June, the company will determine the fastest pathway to both the US and European markets.

Penetrating the brain

Funding was awarded to Cypralis by the Alzheimer’s Drug Discovery Foundation (ADDF) to assist in the development of new cyclophilin inhibitors for neurodegenerative diseases.

This money will be used to extend Cypralis’ ‘hit-to-lead’ medicinal chemistry and broaden its library of novel brain-penetrant cyclophilin inhibitors while also continuing to partner with Janssen in the generation of a new class of CNS penetrant.

There is a lot of potential in cyclophilin D as a novel target for degenerative diseases but no group has published on compounds that combine sub-type selectivity and brain penetration, noted Dr Michael Peel, CSO of Cypralis. “If data from the ADDF funding is encouraging, Cypralis would expect to initiate a lead optimisation campaign in early 2018 with the goal of generating a novel pre-clinical candidate for this extremely challenging and devastating disease.”

Eyes front

Aura Biosciences has enrolled and dosed the first patient in its Phase Ib clinical trial of light-activated AU-011, a targeted therapy for the treatment of ocular melanoma.

Ocular melanoma is a rare and aggressive form of eye cancer with no current targeted therapies available. AU-011 is administered through an intravitreal injection into the eye and once activated with an ophthalmic laser targets the membranes of tumour cells selectively.

The trial will evaluate the safety of two dose levels of AU-011 for the treatment of patients with small-to-medium primary ocular melanoma. Patients enrolled in the trial must be treatment-naïve and have a confirmed ocular melanoma diagnosis.

This treatment has been granted fast track designation by the FDA.

Keeping abreast with abemaciclib

Lilly revealed Phase III results of its MONARCH 2 breast cancer study, evaluating abemaciclib in combination with fulvestrant in the treatment of advanced breast cancer.

Designed to evaluate the efficacy and safety of abemaciclib in combination with fulvestrant, in patients with advanced (locoregionally recurrent or metastatic) breast cancer, the primary endpoint of progression-free survival was met.

“We are excited about the outcome of our first Phase III study for abemaciclib. These data are an important milestone in our goal of bringing abemaciclib to patients with advanced breast cancer, and we look forward to our upcoming conversations with regulators,” said Dr Levi Garraway, PhD, senior vice president, global development and medical affairs, Lilly Oncology.

Breathing easier

Positive interim Phase II results were reported by Heat Biologics for its trial assessing HS-110 in combination with a checkpoint inhibitor in the treatment of lung cancer.

In the trial 12 of the 15 patients that completed the HS-110/nivolumab (Bristol-Myers Squibb anti-PD-1 checkpoint inhibitor Opdivo) combination treatment were evaluated with ELISPOT analysis. The results of the evaluation suggest that HS-110 is important in tumour reduction and may enhance the efficacy of checkpoint inhibitors in lung cancer patients.

“Our results appear to further validate the expected mechanism of action of our approach in combination with checkpoint inhibitors, with a continuing trend towards early and sustained T cell activation in the peripheral blood cells. All patients who mounted a sustained immune response to HS-110 exhibited substantial tumour reduction,” said Jeff Hutchins, PhD, Heat’s chief scientific officer and senior vice president of preclinical development.

Orphan designation for inebilizumab

Orphan designation was granted to AstraZeneca’s inebilizumab by the EMA for the treatment of neuromyelitis optica spectrum disorder (NMOSD).

NMOSD is a rare-life-threatening autoimmune disease of the central nervous system in which the body’s immune system attacks healthy cells, most commonly un the optic nerves and spinal cord, resulting in severe damage. With no current cure or approved medicine for this condition there is a significant unmet need for NMOSD patients.

Developed by AstraZeneca’s global biologics research and development arm, MedImmune, inebilizumab is currently in Phase IIb of clinical development.

Progressing therapy for MS

A new drug to treat multiple sclerosis (MS) was approved by the FDA. Ocrevus (ocrelizumab) is the first drug approved in the US for primary progressive MS. It is administered through intravenous infusion by a healthcare professional.

Dr Billy Dunn, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research said, “This therapy not only provides another treatment option for those with relapsing MS, but for the first time provides an approved therapy for those with primary progressive MS.”

A diabetes cure?

Researchers from the University of California have released findings, published in New Scientist, that a daily dose of a new drug could effectively ‘cure’ type 2 diabetes.

The drug works by inhibiting an enzyme called low molecular weight protein tyrosine phosphatase (LMPTP), which is found in the liver and appears to cause cells to become resistant to insulin. Researchers administered the drug orally to mice daily without incurring any side effects.

“This could lead to a new therapeutic strategy for treating type 2 diabetes,” said Stephanie Stanford, University of California, San Diego.

Emily Burns of Diabetes UK added, “If this new drug works as described, it could be used to reverse insulin resistance, but we need to know first if it does that safely in people.”

Implantable AIDS treatment

The NIH has awarded a grant to researchers to the University of North Carolina at Chapel Hill for the development of a new implantable drug delivery system for the treatment of HIV/AIDS.

This new system is in the form of an injectable formulation that contains an anti-HIV drug, a polymer and a solvent. Once injected, the compounds solidify in the skin and then as the polymer slowly degrades the anti-HIV drugs gets released slowly into the patient’s system.

Current treatment to prevent HIV-infection is in the form of a pill taken once-daily, however, adherence is an issue. An injectable implant would solve this issue.

APPROACH-ing success

The Phase III APPROACH study of volanesoren met its primary endpoint of reducing triglyceride levels in patients with familial chylomicronaemia syndrome (FCS).

FCS is a severe, rare genetic disorder that is characterised by extremely high levels of triglycerides and the risk of recurrent, potentially fatal pancreatitis. Volanesoren is an antisense drug in development designed to reduce the production of ApoC-III (a protein produced in the liver that is important in the regulation of plasma triglycerides).

There are currently very few effective treatment options for patients with FCS. “The success of APPROACH represents an important milestone towards our first regulatory submissions for volanesoren in the US, Europe and Canada in 2017,” reported Dr Louis O'Dea, chief medical officer of Akcea Therapeutics. “We seek to bring this new treatment as expeditiously as possible to FCS patients who have a high unmet need with potentially life-threatening consequences.”

Never neglect your feet

A Geneva-based non-profit R&D organisation (Drugs for Neglected Diseases initiative – DNDi) and Eisai are combining to tackle eumycetoma using a compound that is already available.

Eumycetoma is a fungal infection that causes swelling of the hands and feet and in severe cases can lead to amputations. Although there is a current treatment for the condition it is ineffective and expensive.

Eisai will develop and manufacture an investigational reagent based on the active form of fosravuconazole. DNDi will then conduct a comparative study with this agent and will publish the results in 2019.