Sickle cell disease has drawn attention from drug developers seeking to prevent or treat the painful vaso-occlusive crises that occur when misshapen blood cells block key vessels and damage organs.

With rivipansel, GlycoMimetics and Pfizer were aiming for a specific niche: shortening hospital stays for patients experiencing VOCs by reducing cell adhesion and inflammation. GlycoMimetics and Pfizer hypothesized that rivipansel would do so because it blocks several proteins that contribute to cell adhesion.

Payers would be eager to see a treatment that can achieve earlier discharges, because the average hospital sickle-cell related hospital stay costs $15,000. Taken together, they account for 57% of the $3 billion the U.S. spends annually to treat this condition.

The RESET trial enrolled 341 patients. In addition to pain management and other standard-of-care treatments, patients received either rivipansel or a placebo with the hope that those receiving the active treatment would meet readiness-to-discharge criteria.

Failure on this primary measure, and secondary metrics such as time to discharge and opioid pain-reliever consumption, means that at best rivipansel will need a second pivotal trial to enable regulatory submission.

Pfizer paid $22.5 million in 2011 for rights to rivipansel in a deal that promised $115 million in fees for clinical achievements, $70 million for regulatory filings and approvals, $135 million in sales milestones, and royalties. The regulatory and sales-based reimbursement look all but impossible now, cutting GlycoMimetics, which has no marketed products, off from a key revenue source.

The company reported $184 million in cash as of June 30, which it says will be enough to fund pipeline development. Research and development expenditures totaled $13.1 million during the second quarter, while general and administrative costs amounted to $3.8 million.

With its market capitalization now at $154 million, investors clearly will need to be persuaded of the promise of GlycoMimetics’ Phase 3 drug for acute myeloid leukemia, uproleselan, before shares rise again.

Two other drugs are in late-stage development as preventive treatments for sickle-cell-driven VOCs. Novartis has submitted crizanlizumab to the U.S. Food and Drug Administration for approval, while Global Blood Therapeutics is in Phase 3 development with voxelotor.

Bluebird bio’s gene therapy Zynteglo, now approved for beta thalassemia in the European Union, is also being tested in sickle cell patients.