As with recent rejections for Biogen and Scholar Rock, manufacturing issues stymied a regulatory bid from Fortress Biotech and Sentynl Therapeutics. Fortress said the FDA did not flag problems with the drug’s safety or efficacy.
The FDA has rejected Fortress Biotech and Sentynl Therapeutics’ investigational treatment for Menkes disease, a rare, genetic disorder that usually leads to death by 3 years of age.
In its complete response letter, the regulator cited issues at the manufacturing facility where the drug is produced, Fortress announced Wednesday, noting that the plant in question has already responded to these observations. The FDA did not find any other deficiencies with the application, nor did it flag problems with the drug’s efficacy or safety data, according to Fortress.
Manufacturing has become a recurring theme in recent FDA rejections. Biogen’s high-dose formulation for Spinraza and Scholar Rock’s apitegromab were both also rejected due to issues at a manufacturing site, as opposed to anything about the therapies themselves. Sentynl acquired the asset, called CUTX-101, in February 2021 for $20 million. The company plans to seek a meeting with the agency to discuss a resubmission. If approved, Fortress, through a subsidiary, will be entitled to up to $129 million in aggregate development and sales milestones, plus royalties on net sales.
Afflicting 1 in 100,000 infants, Menkes disease is characterized by sparse and depigmented hair, seizures, intellectual disability and developmental delays. Patients with the disease also fail to gain weight or grow as expected and suffer from the deterioration of the nervous system.
Menkes disease is caused by mutations to the ATP7A gene, which under healthy conditions produces a protein that helps maintain levels of copper throughout the body. Genetic alterations in Menkes disease disrupt the otherwise normal distribution of copper, resulting in deficiencies in some organs but toxic excesses in others.
CUTX-101 is a subcutaneous formulation of copper histidinate, which in an October 2021 readout reduced the risk of death by 80% in treated patients as compared with untreated historical controls. The midstage trial also found that early intervention with CUTX-101 resulted in a median overall survival of 177.1 months, versus 16.1 months in controls.
The FDA in January 2020 gave CUTX-101 its rare pediatric disease designation. If approved, the drug could receive a priority review voucher, which Sentynl has agreed to transfer to Fortress.
The rare disease space has seen a rush of activity in recent months. FDA Commissioner Marty Makary has publicly said multiple times that his office is open to granting expedited approval for drugs in this space, but drugmakers are still being hit with surprise rejections. In July, for instance, Capricor’s Duchenne muscular dystrophy drug was turned away, and Ultragenyx was handed a denial in Sanfilippo syndrome type A. The following month, however, the FDA signed off on four industry firsts in the rare disease space: Jazz Pharmaceuticals’ Modeyso for Glioma, Insmed’s Brinsupri for non-cystic fibrosis bronchiectasis, Precigen’s Papzimeos for recurrent respiratory papillomatosis and Ionis’ Dawnzera for hereditary angioedema.
