The FDA has placed a phase 1/2 trial of Passage Bio’s GM1 gangliosidosis gene therapy PBGM01 on clinical hold pending further assessment of the risks associated with its delivery device, delaying the start of the study until around the end of the year.
Passage Bio, a James Wilson-founded gene therapy startup, raised two private megarounds last year and completed a $216 million IPO in February, giving it the means to advance a pipeline led by its GM1 prospect into the clinic. That plan advanced in June when Passage Bio filed an IND for PBGM01 but has now hit a snag.
After receiving the filing, the FDA placed the IND on clinical hold pending additional risk assessments of the biocompatibility of the proposed delivery device. PBGM01, like all of Passage Bio’s lead prospects, is delivered through intra cisterna magna (ICM) injection at the craniocervical junction.
Passage Bio thinks ICM delivery gives improved biodistribution to the brain and spinal cord, as well as lower toxicity and reduced impact of neutralizing antibodies. The potential for ICM delivery to yield greater protein expression than other delivery routes led Passage Bio to select it as the likely method of administration for its lead candidates.
However, Passage Bio knew the ICM delivery method carried some potential or perceived risks, as it described to investors in the IPO paperwork it published earlier this year.
“While this method of administration has been available for decades, its use for therapies is relatively new, no therapies are currently approved using ICM administration, and it may be perceived as having greater risk than more common methods of administration, such as intravenous injection,” Passage Bio wrote.
The clinical hold suggests the FDA thinks those perceptions of greater risk may have some merit. Passage Bio, which is still waiting for written feedback from the FDA, is “evaluating options for conducting additional risk assessments” to allay the concerns and get the clinical hold lifted.
As it stands, Passage Bio only expects a short delay. At the time of its IPO filing, Passage Bio planned to start the phase 1/2 trial in the second half of 2020. With the IND on clinical hold, Passage Bio now expects to dose the first patient in the fourth quarter of 2020 or first quarter of 2021. Passage Bio expects to report 30-day safety and biomarker data late in the first half of 2021.