Fulcrum’s Clinical Hold Challenges the Sickle Cell Space

Fulcrum Therapeutics’ hopes for its potential sickle cell disease (SCD) treatment, FTX-6058, have been put on hold after the US Food and Drug Administration (FDA) placed a full clinical hold on the Investigational New Drug application. The setback has put a pause on the development of the drug, whose potential to improve the lives of those suffering from SCD could be game-changing.

Fulcrum has been forced to suspend the dosing of all patients in the Phase Ib trial of their candidate, due to the FDA’s verbal order issued on Thursday. In the next 30 days, a formal Clinical Hold Letter is expected to be released by the regulatory authorities.

The FDA has placed a hold on further clinical trials, citing previously reported data as the cause. This decision has raised questions about the safety and efficacy of the drug in question.

Robert Gould, Ph.D., interim president and CEO of Fulcrum, has expressed that patient safety is of the utmost importance. “Patient safety remains paramount to me,” he stated.

The company is working diligently with the FDA to swiftly resolve the hold and move forward.

Fulcrum is committed to shedding light on the modulation of the PRC2 complex and its preclinical data. With the aim of uncovering answers to important questions, Fulcrum is taking the initiative to make meaningful progress in this area.

Fulcrum has uncovered a remarkable new oral small molecule inhibitor, FTX-6058, that targets the Embryonic Ectoderm Development (EED) subunit of the PRC2 protein complex. This complex plays an integral role in human development, and by targeting EED with FTX-6058, Fulcrum has been able to increase fetal hemoglobin levels. This groundbreaking discovery could have far-reaching implications for the future of medicine.

In August 2021, a Phase I, multiple-ascending dose study of FTX-60589 revealed promising results in healthy adults, demonstrating increases in immature red blood cells carrying fetal hemoglobin in a dose-proportional manner, providing evidence of the drug’s biological activity.

SCD Trips Up the Industry

Last week was a tough one for the Sickle Cell community, as Graphite Bio pulled the plug on their SCD program, nulabeglogene autogedtemcel (nula-cel), after pausing the trial back in January due to a serious adverse event likely linked to the drug. It was a major blow to hopes of finding a potential new treatment option for those with the condition.

On the same day, Novartis made a bold move, discontinuing its ex vivo Sickle Cell Disease program in partnership with Intellia Therapeutics. The decision came as a surprise to many in the scientific community, indicating a shift in Novartis’ research focus.

In January, Novartis experienced a setback when its approved SCD therapeutic, Adakveo (crizanlizumab), failed its Phase III clinical trial. Although the Swiss multinational is currently working with regulators to determine the next steps for Adakevo, the results of the trial have certainly been disappointing.

Sangamo Therapeutics announced in its full-year financial results that it will be ceasing further material investment in its SCD program BIVV003 after completing its Phase I/II study. Instead, the company will be seeking partnerships to propel BIVV003 into Phase III.

Safety has become a major obstacle for those developing gene-based therapies for Spinal Cord Diseases, making the drug discovery process a challenge. Despite the difficulties, the commitment to finding a successful treatment remains strong.

In December 2021, bluebird bio’s SCD candidate lovotibeglogene autotemcel was briefly placed on partial suspension after a patient receiving the gene therapy developed transfusion-dependent anemia. However, the FDA lifted the suspension a year later in December 2022, allowing the therapy to continue on its journey to becoming a potentially revolutionary treatment for sickle cell disease.

Despite the challenges that come with it, some businesses have achieved remarkable success in the field. Whether it be through innovative strategies or sheer perseverance, these companies have demonstrated that success is still achievable in the face of adversity. From creating new opportunities to finding ways to maximize potential, these companies have shown that dedication and hard work can pay off in a big way.

Vertex Pharmaceuticals and CRISPR Therapeutics are eagerly awaiting the launch of exagamglogene autotemcel, a revolutionary one-time treatment for SCD. After being granted an expedited review from the FDA in September 2022, the pharma partners are expecting to complete the review in the first quarter of 2023. This groundbreaking treatment promises to be a game changer for SCD patients.

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