Two years after an errant statistical analysis derailed Emmaus Life Sciences Inc.'s initial efforts to gain approval for its pharmaceutical-grade L-glutamine, a treatment for adults and children with sickle cell disease (SCD), the Torrance, Calif.-based company is back on track, seeking priority review for its new drug application (NDA). If approved, its NDA, could clear the path for the candidate to become the first new therapy approved for the condition in nearly 20 years.

Though L-glutamine is widely sold as a nutritional supplement, Emmaus' CEO and co-founder, Yutaka Niihara said he expects that doctors' concerns about the purity of such over-the-counter products and the assurance conveyed by FDA approval of the company's version will help the firm capture market share among patients who would take as much as 30 grams of the amino acid daily for life. While challenging, the feat is not unprecedented, having been accomplished by products such as Lovaza (omega-3-acid ethyl esters, Glaxosmithkline plc) and Niaspan (nicotinic acid), both of which approached $1 billion in annual sales before generic competition eroded sales.

Data from Emmaus' pivotal phase III trial – a 230-patient randomized, double-blind study that concluded in 2014 – demonstrated a 25 percent reduction in the median frequency of sickle cell crises for patients with sickle cell anemia or sickle beta 0-thalassemia provided with L-glutamine vs. placebo at 48 weeks, the study's primary endpoint. Investigators also found a 33 percent reduction in the median frequency of hospitalizations at week 48.

Niihara has been actively engaged in SCD research and SCD patient care for more than 20 years, primarily at the University of California, Los Angeles, and the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. In research with his mentors he found that "sickled red blood cells suck L-glutamine like a dry sponge sucking up water," he told BioWorld Today. That led him to first study the need for L-glutamine in red blood cells and then to explore its function. What he found was that L-glutamine helped improve the regulation of oxidative stress on red blood cells, helping normalize their shape and, in turn, reducing endothelial adhesion, or "stickiness" of red blood cells, leading to better blood flow. (See BioWorld Today, Oct. 12, 2012.)

While errors in an initial analysis of the company's phase III study of the effect conducted by Emmaus's former clinical research organization led to a delay in what had been planned as a 2014 filing of the NDA, an independent third-party evaluation the company provided the agency in February addressed the situation, leaving the company "very confident" in the outcomes of the trial and alignment of the analysis with the agency's expectation, Niihara said.

If approved, the company plans to market its L-glutamine treatment in the U.S. either through a strategic partnership or by building its own targeted sales force of about 30 sales representatives. Outside the U.S., it would rely on strategic partnerships, Niihara said.

Emmaus' L-glutamine, currently sourced from Ajinomoto North America Inc. and Kyowa Hakko Bio Co. Ltd., has orphan drug status in both the U.S. and Europe and a fast track designation from the FDA. The company plans to submit a marketing authorization application to the EMA before the end of this year. The company also sells L-glutamine powder as a prescription product for short bowel syndrome under the brand name Nutrestore.

SCD is an inherited blood disorder caused by a single gene mutation. It's characterized by the production of an altered form of hemoglobin which polymerizes and becomes fibrous, causing red blood cells to become rigid and change form so that they appear sickle-shaped instead of soft and rounded. Patients with SCD suffer from lifelong complications, including anemia, infections, stroke, tissue damage, organ failure, intense painful episodes and premature death. Sickle cell crisis causes excruciating pain as a result of insufficient oxygen being delivered to tissue.

The only FDA-approved treatment for the condition is hydroxyurea, a chemotherapeutic agent first approved for adults with SCD by the FDA in 1998, though often used off-label in children. It is available in both generic and branded formulations. But, unfortunately, despite the National Heart, Lung, and Blood Institute's recommendations, hydroxyurea is not regularly prescribed and adherence to the therapy is poor, according to a new report on the condition, recently published by the American Society of Hematology.