Aiming to brush last year's flop aside, Fulcrum sees shares skyrocket on early look at sickle cell program
Fulcrum Therapeutics $FULC is looking to rebound after the Phase II flop of an old GlaxoSmithKline drug slashed their market value in half last August. And if Tuesday’s stock movement is any indication, investors like what they see.
At an interim analysis of a Phase I study, Fulcrum reported that their program designed to treat inherited blood disorders hit a statistically significant rate in two key measurements, the company announced Tuesday morning. The results sent Fulcrum shares skyrocketing more than 125%, sending the stock price back above what it had been before last year’s whiff.
The program, known as FTX-6058, is being developed for sickle cell disease and non-sickle cell hemoglobinopathies, such as beta thalassemia.
Tuesday’s results come from a randomized and double-blinded study looking at healthy volunteers over the course of 14 days. Fulcrum ran both single-ascending dose and multiple-ascending dose portions of the trial, with Tuesday’s data coming from the latter where individuals received either 2 mg, 6 mg or 10 mg doses daily.
Across the cohorts, researchers saw dose proportional inductions in HBG mRNA and accompanying increases in F-reticulocytes, two markers on which investors keyed in. The 10 mg dose in particular proved positive, Fulcrum noted, with FTX-6058 reaching mean changes of 4.5-fold and 4.2-fold in each measure, respectively.
The program hit the 4.5-fold increase for HBG mRNA mean fold induction at the 14-day mark, while notching the 4.2-fold increase in F-reticulocytes at the 21-to-24-day safety follow-up. Both assessments hit p-values of p<0.0001.
“Preclinically, we demonstrated consistent 2-3-fold induction of HBG mRNA and HbF protein both in vitro and in vivo,” CEO Bryan Stuart said in a statement. He continued that the clinical results “demonstrate the first evidence that FTX-6058 can achieve or exceed these preclinical thresholds predicted to provide meaningful clinical benefits to individuals with SCD.”
Analysts were surprised but pleased with the increases, with Stifel’s Dae Gon Ha noting any HBG mRNA induction would have been seen as a positive. Ha highlighted, however, the small trial population, the short duration and the fact that participants did not have sickle cell disease are “key caveats” to the safety aspect of Tuesday’s results.
Fulcrum reported few trial discontinuations and only one serious side effect at Grade 4, an asymptomatic increase in creatine phosphokinase at the 10 mg dose.
“As an epigenetic-targeting drug that likely requires chronic dosing in patients, at this time we cannot rule out potential safety/tolerability signals upon extended period of dosing,” Ha wrote to investors. “Thus, while we are encouraged by the safety progress to-date in this 14-day study, we anticipate a more comprehensive safety overview to emerge from subsequent trials.”
Looking ahead, Fulcrum plans to launch a Phase Ib study in sickle cell patients in the fourth quarter, which will dose participants over three months. Both Ha and SVB Leerink’s Joseph Schwartz wrote they’ll be keeping an eye on how the longer treatment period affects the two measurements reported Tuesday, as well as the durability of treatment effect.
Fulcrum also expects to submit an IND in non-SCD hemoglobinopathies by the end of 2021.
Tuesday’s news comes almost a year to the day after Fulcrum took a nosedive off a Phase II fail of the old GSK drug losmapimod. Researchers had been looking at whether the p38α/β MAPK inhibitor could significantly reduce a certain gene’s expression in facioscapulohumeral muscular dystrophy after 16 weeks.