Brian Culley, CEO of Adventrx Pharmaceuticals Inc., is a busy man these days. Not only is his company readying itself for an important Phase III trial, but he also is in the midst of organizing the first Sickle Cell Disease Therapeutics Conference that will be held this week, Sept. 19, in New York City.

The meeting grew out of the idea of holding a company-sponsored "open house" for healthcare analysts and key opinion leaders, but then expanded to a much broader concept, Culley told BioWorld Insight.

The one-day conference is intended to serve as a forum to raise awareness for sickle cell disease (SCD) and will include presentations from companies in the SCD space and discussions with experts describing the latest advancements and future trends for patients.

A Timely Event

"The event is certainly timely because new therapies for sickle cell disease are on the horizon," Culley explained. "Although the disease was first identified over 100 years ago, only one FDA-approved drug is available, and none are available to treat an ongoing vaso-occlusive crisis or the underlying ischemia and infarction that reduce the average life expectancy of people suffering from the disease to less than 40 years. Fortunately, the situation is about to change because several companies are reporting that they are advancing innovative potential treatments for sickle cell disease and its associated complications into clinical trials."

SCD is a genetic disease causing amino acid substitution on the beta-chain of hemoglobin. The red blood cells become sickle-shaped (crescent shaped) and have difficulty passing through small blood vessels. Normal red blood cells live for about 120 days before they are replaced. In contrast, sickle red blood cells are destroyed in about 16 days, and cannot always be replaced quickly enough. As a result, people with SCD are often anemic. The complications of sickle cell disease occur when sickle-shaped red blood cells block veins which then can cause pain in the arms, legs, back and stomach, bones, skin and other parts of the body.

The disease is most common in West and Central Africa, and, according to the Sickle Cell Disease Association of America Inc., approximately 70,000 to 100,000 individuals in the U.S. have sickle cell disease and 3 million carry the sickle cell trait.

Adventrx is currently in discussions with the FDA to finalize a Phase III trial design of ANX-188 for alleviating the painful crisis in sickle cell anemia, Culley said. ANX-188, which the company acquired the rights to last year, is an aqueous solution of a purified form of poloxamer 188, a nonionic, block copolymer that has been found to improve microvascular blood flow by reducing viscosity.

A 250-patient Phase III trial, performed by GlaxoSmithKline plc, the previous sponsor, narrowly missed the primary endpoint in patients of all ages. Adventrx plans to repeat the trial with about 400 patients enrolled at 30 to 40 centers.

The company has more than $43 million in the bank to fund the SCD trial. However, to maximize the potential of ANX-188 that protects tissue from ischemic injury and reduces end-organ damage, it has been evaluating the product in other indications but would need partners to carry the programs forward, Culley noted.

SCD Therapies Move to Trials

There are several companies presenting at the Sickle Cell Disease Therapeutics Conference including AesRx LLC, of Newton, Mass., which has started a Phase I/IIa trial of its orally bio-available Aes-103 anti-sickling agent in patients with sickle cell disease. The trial, conducted as part of an ongoing collaboration with the National Institutes of Health, will examine the safety and tolerability of the oral small molecule in patients with stable disease, and also evaluate Aes-103's pharmacokinetic and pharmacodynamics properties. (See BioWorld Today, May 15, 2012.)

Discovered by researchers at Virginia Commonwealth University, Aes-103 works by increasing the affinity of sickle hemoglobin for oxygen. Because only red blood cells with no bound oxygen will sickle, increasing the ability of sickle red blood cells to bind oxygen reduces the number of cells that can sickle.

Another conference participant, Erytech Pharma, of Lyon, France, has a sickle cell treatment, Enhoxy, a human erythrocytes encapsulating inositol hexaphosphate, which enhances the oxygenation properties of red blood cells by reducing their oxygen-hemoglobin affinity and allowing them to release more oxygen. (See BioWorld Today, June 14, 2012.)

In March 2012, HemaQuest Pharmaceuticals Inc. closed a $13 million extension of its Series B financing to fund a randomized, double-blind, placebo-controlled Phase IIb clinical study evaluating lead product candidate HQK-1001 in patients with sickle cell disease. The study will enroll patients at a dozen or more sites in the U.S. and at sites in Lebanon, Egypt and Jamaica – countries with a high prevalence of sickle cell.

HQK-1001 belongs to a class of compounds designated as short chain fatty acid derivatives (SCFADs), which have been shown to stimulate fetal hemoglobin expression and red blood cell production. (See BioWorld Today, March 13, 2012.)

Emmaus Medical Inc., a specialty pharmaceutical and regenerative medicine company, and subsidiary of Emmaus Life Sciences Inc., is conducting a Phase III trial on levoglutamide (L-glutamine) as a treatment for sickle cell disease. Research is being conducted at more than 30 clinical trial sites around the country with more than 175 people presently enrolled. The company anticipates total enrollment of more than 200 and aims to complete the trial in 2013. (See BioWorld Today, July 18, 2012.)

bluebird bio, of Cambridge, Mass., which is developing gene therapies for severe genetic disorders including SCD, completed a $60 million Series D financing to fuel its clinical programs. (See BioWorld Today, July 25, 2012.)

Based on promising early clinical proof of concept results, bluebird bio plans to initiate a Phase II/III clinical study in childhood cerebral adrenoleukodystrophy (CCALD) in the U.S. and Europe in 2013, as well as a second U.S.-based Phase I/II study in beta thalassemia next year. In addition, the company said that it expects to initiate a more extensive sickle cell disease development program and invest in manufacturing, clinical and commercial infrastructure to support the upcoming clinical trials and pre-commercial launch activities.