Emmaus bags FDA approval for sickle cell therapy; now comes the hard part

An FDA greenlight for sickle cell disease therapy Endari has catapulted its developer, Emmaus Medical, into the spotlight, but commercializing the new drug could be challenging.

The approval means the privately-held biotech has ended a 20-year drought in new therapies for sickle cell disease (SCD), an inherited disease in which red blood cells are abnormally shaped and can't deliver oxygen as effectively to body tissues. Prior to this, the only other drug approved for the disease in the U.S. was hydroxyurea.

Most of the 100,000 people in the U.S. with SCD are covered by Medicare and Medicaid, so the company will need to pitch the price of the drug at a level that will ensure access to patients is not obstructed by payer resistance. Its job is made harder by the fact that the active ingredient is already widely used as a dietary supplement.

For now, the California biotech, led by Yutaka Niihara M.D., is playing its cards pretty close to its chest. It said it was planning a launch in the fourth quarter of the year, but isn't showing its hand on pricing just yet, limiting itself to a statement that it will price Endari at a "reasonable" level to ensure patient access. An Endpoints report suggested the company is looking at charging somewhere between $11,000 and $18,000 a year for the product.

Endari is an oral powder formulation of L-glutamate, an amino acid the company already sells as a nutritional product they claim helps manage short bowel disease. The rationale for using it in SCD is that glutamine is a precursor of an enzyme called NAD, which is thought to be important for the functioning of the oxygen-carrying hemoglobin molecule.

People with SCD can elect to self-medicate with L-glutamate supplements, but these are not reimbursable and cost tens of dollars per month at the doses required to show an effect in SCD. These products also have variable quality, so are a bit of a lottery for patients, and Emmaus said its pharmaceutical-grade version tackles that problem.

Early experiments showed that L-glutamate could reduce the sickling of red blood cells and help maintain hemoglobin's capacity to carry oxygen. And that promise was backed up in clinical trials that showed the drug could reduce the number of painful attacks or crises that afflict SCD patients by around one over a 48-week period.

There was a lot of debate over the clinical significance of that reduction at an FDA advisory committee meeting in May, but on balance, panelists concluded that was an important reduction, particularly in patents at the more severe end of the SCD spectrum who may have four or more attacks each year.

There was also concern about a high drop-out rate among patients on Endari compared to placebo, but a number of these came from a clinical investigation site suspected of misconduct. Emmaus opted to exclude those patients from its final analysis, and it seems the FDA was happy with its explanation.

The agency's decision to approve was also likely swayed by secondary endpoint data, including a 41% reduction in hospital days and a 58% cut in acute chest syndrome—one of the most serious complications of SCD—and the fact that the benefit came on top of hydroxyurea therapy.

Meanwhile, other drugs for SCD are winging their way through development, including Pfizer and GlycoMimetics' rivipansel, Novartis' crizanlizumab and Global Blood Therapeutics' GBT440, as well as a gene therapy candidate from Bluebird Bio.