Biotech Companies Expected to Release Key Study Results in Early 2016

Targeted disorders include breast cancer, atopic dermatitis, and phenylketonuria

Four biotech firms plan to announce important clinical trial findings in the first quarter of 2016, according to a report posted on the 24/7 Wall St. website.

Zafgen Inc. is readying top-line results from a phase III study of beloranib in patients with Prader–Willi syndrome (PWS). The study’s objective is to evaluate the efficacy and safety of beloranib in PWS patients during six months of randomized treatment, followed by a six-month open-label extension. The study includes 108 patients with PWS enrolled at sites in the U.S.

Beloranib is being studied as a first-in-class methionine aminopeptidase 2 (MetAP2) inhibitor for the treatment of obesity, a key characteristic of PWS. MetAP2 inhibitors reduce the production of fatty-acid molecules by the liver and help to convert stored fats into useful energy. By targeting this key enzyme, beloranib restores the balance between the production and utilization of fat, resulting in positive metabolic cascades.

Aquinox Pharmaceuticals completed enrollment in its phase II study of AQX-1125 in mid 2015, and the company expects to release top-line results in the first quarter of 2016. AQX-1125 reduces immune-cell activation and migration to sites of inflammation in patients with atopic dermatitis.

The randomized, double-blind, placebo-controlled KINSHIP trial is evaluating the efficacy and safety of AQX-1125 in approximately 50 adult patients with mild-to-moderate atopic dermatitis at research centers in Canada. The trial’s primary endpoint is the change from baseline in the Total Lesion Symptom Score (TLSS) after 12 weeks of treatment.

AQX-1125 is an activator of SHIP1, which controls the PI3K cellular signaling pathway. If the PI3K pathway is overactive, immune cells can produce an abundance of pro-inflammatory signaling molecules and can migrate to and concentrate in tissues, resulting in excessive or chronic inflammation. SHIP1 is predominantly expressed in cells derived from bone-marrow tissues, which are mainly immune cells. Therefore, drugs that activate SHIP1 can reduce the function and migration of immune cells and have an anti-inflammatory effect. By controlling the PI3K pathway, AQX-1125 reduces immune cell function and migration.

BioMarin Pharmaceutical Inc. is scheduled to report phase III results for pegvaliase (pegylated recombinant phenylalanine ammonia lyase [PEG-PAL]) in the first quarter of this year. PEG-PAL is in pivotal studies as a potential treatment for adult patients with phenylketonuria (PKU).

Pegvaliase substitutes the phenylalanine hydroxylase (PAH) enzyme in PKU by breaking down phenylalanine (Phe). It is being developed as a potential therapy for patients whose blood Phe levels are not adequately controlled by sapropterin dihydrochloride (Kuvan, Biomarin) or who have trouble controlling and maintaining their Phe levels. The treatment has received an orphan drug designation from the FDA.

PKU is a genetic condition requiring lifelong management. In individuals with this disorder, the PAH enzyme is either missing or not working properly, which can cause a buildup of Phe in the blood. Phe is an amino acid found in many foods, especially those high in protein, such as chicken, meat, eggs, dairy, nuts, grains, and legumes. High or unstable blood Phe levels can cause a variety of symptoms, including mental, behavioral, neurological, and physical problems.

Puma Biotechnology Inc. plans to proceed with regulatory filing for neratinib (PB272) for the extended adjuvant treatment of breast cancer during the first quarter of 2016. Neratinib is an irreversible tyrosine kinase inhibitor (TKI) that blocks signal transduction through the epidermal growth factor receptors HER1, HER2, and HER4. Puma believes that neratinib has clinical application in the treatment of several cancers, including breast cancer and gastric cancer. The company’s initial focus is on the development of neratinib as an oral treatment for patients with HER2-positive breast cancer.

Results from a phase II study of neratinib monotherapy in 136 patients with HER2-positive metastatic breast cancer were published in the March 2010 issue of the Journal of Clinical Oncology. The efficacy results from this study showed that the objective response rates were 24% in patients who had received prior trastuzumab treatment and 56% for patients with no prior trastuzumab treatment. In addition, median progression-free survival was 22 weeks for the patients who had received prior trastuzumab and 40 weeks for the patients who had not received prior trastuzumab.

A significant amount of risk is involved in bringing drug candidates to market through clinical trials, and the FDA’s ultimate approval decision can make or break a company, the 24/7 Wall St. report notes.

Sources: 24/7 Wall St.; January 2, 2016; Zafgen Inc.; 2015; Aquinox Pharmaceuticals; 2015; BioMarin Pharmaceutical Inc.; 2016; and Puma Biotechnology; 2015.