FDA Puts MacroGenics Phase 1 On Partial Hold After Liver Complications Arise

The U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on MacroGenics’ Phase 1 trial for the single dose and combination studies of the MGD009 cancer drug after patients developed liver complications.

Following the partial clinical hold, no new patients will be enrolled for clinical trials of the MGD009 drug. The company said that although no new patients could be enrolled, existing participants would continue with the study.

MacroGenics hopeful to bounce back soon

In a statement, MacroGenics said the study had to be stopped after patients recorded “adverse hepatic” events on the MGD009 monotherapy trial. The company said it had also recorded “reversible elevations of transaminases with or without concurrent elevations of bilirubin.”

Reversible elevations of transaminases could be illustrative of inflammation or damage to cells in the liver. Higher than normal levels of bilirubin in the blood might indicate liver problems.

MacroGenics is a clinical-stage biopharmaceutical company working on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, described the liver side effects as uncomplicated and short-lived in duration. The company says that the FDA knows of its plans to amend the existing MGD009 studies with additional supportive care to mitigate these events.

“The FDA has placed the trials on partial clinical hold, pending review of additional details regarding these events, and satisfactory review of the planned amendments to the monotherapy and combination study protocols and related documents. MacroGenics will be working closely with the FDA to review these events and seek to resolve this clinical hold,” the statement read.

The president and  chief executive officer of the Rockville, Maryland-based MacroGenics, Scott Koenig said they were working with the FDA and they would provide an update as soon as they had one. “As we’ve identified to the FDA, we believe that transaminitis observed in patients administered MGD009 was likely a cytokine-mediated event,” Koenig said.

Koenig was quick to point out that this setback will not affect ongoing clinical studies for other therapies in the company’s pipeline, which are “enoblituzumab and MGC018, our other B7-H3-targeted molecules.”

MacroGenics expects that the partial hold will be resolved quickly, allowing the MGD009 clinical trials to continue as early as January 2019.

Bispecifics industry hits turbulence

Not everyone is optimistic that MacroGenics can bounce back so soon, amid fears that this setback could have a contagion effect on other companies in the bispecifics field.

The Evaluate website said the bispecifics field was not developing as rapidly as anticipated and has recently recorded several setbacks. It pointed out that in the autumn, Johnson & Johnson’s CD3/CD123-targeting project had been halted for the second time.

In addition, the website said Affimed’s AFM11 was put on hold in October after a patient died and two more experienced life-threatening events, while last year, Johnson & Johnson “handed back another Macrogenics project, the CD19-targeting duvortuxizumab, at least partly over toxicity concerns.”

MacroGenics, which recruited 118 patients for the Phase 1 clinical trials, is testing the MGD009 bispecific in patients with non-small cell lung, bladder and head and neck cancer, mesothelioma, melanoma, and other B7-H3 positive tumors.

The therapy is one of MacroGenics’ humanized dual-affinity re-targeting antibodies or DART bispecific drug candidates which combines CD3 and B7-H3 targeting and is being developed for solid tumors.

The MGD009 Phase 1 study is designed to characterize the safety and tolerability of the therapy and establish the maximum tolerated dose (MTD) of MGD009 administered to patients every two weeks, the company said on its website.

The study is also assessing pharmacokinetics, pharmacodynamics, and the anti-tumor activity of the drug.

In preclinical studies, MGD009 was shown to enable “the death of B7-H3-producing human cancer cell lines by T-cells. The therapy had also showed that it leads to the prevention of tumor growth and the regression of B7-H3-producing tumors in mice. MGD009 also demonstrated a prolonged half-life (five to six days) when injected into monkeys.”

Predictably, news of the partial clinical hold triggered a massive fall in the company’s stock price, as it reportedly fell by up to 32 percent.

However, the Motley Fool website projected that if the FDA was to accept MicroGenics’ modifications of the MGD009 therapy, the company’s shares could reclaim most, if not all, of their lost ground in the not-so-distant future.