Problems, both manufacturing and financial, with an Austrian fill-finish firm has resulted in a partial hold of a trial of Innate Pharma, the French biotech that has a list of development deals with some of the biggest players in pharma.
Innate today said the FDA has put its Tellomak clinical trial on partial hold because of issues surrounding its fill-finish contractor Rentschler Fill Solutions. The trial is testing lacutamab (IPH4102) in patients with advanced T-cell lymphomas.
The Rankweil, Austria, subcontractor in October suddenly stopped production and filed for bankruptcy.
The FDA is allowing currently enrolled patients to continue on the treatment but will not allow additional enrollees until a new GMP-certified batch is available. Innate said it is working to have the fill-finish work transferred to another contractor and anticipates it can have additional supply available in the second half of 2020.
The U.K.’s Medicines and Healthcare products Regulatory Agency has agreed the trial can continue with the available supply, and Innate is still awaiting word from regulators in France, its home country. It has already suspended the trial in Italy.
The French company pointed out that the FDA did not raise any safety issues related to the clinical supply. It says that is in line with a review by the independent data monitoring committee (IDMC), which “concluded there were no new, unexpected safety issues related to lacutamab, and the product appeared to be well-tolerated among current patients enrolled in the trial.”
Innate said the IDMC determined it would be acceptable to continue recruiting patients in the Tellomak trial if regulatory agencies agreed.
While Austrian regulators had reaffirmed their GMP approval of Rentschler Fill Solutions in October, the company “unilaterally withdrew the Certificate of Conformity of batches” they had produced, including the lacutamab batch being used in the Tellomak trial, and then filed for bankrutpcy.
According to a report in Die Press, Rentschler Fill Solutions, which is also known as Impletio Wirkstoffabfüllung, was formed in 2016. It started filling operations last year but then ran into problems. It laid off about 20 workers last summer. Citing the Alpine Vendor Association (AKV), Die Press reported the CMO had to stop production because of process flow defects.
"Since a restart of the system is not possible in a timely manner, no more bottling can take place in the foreseeable future and no more funds will flow to the company," AKV said. The bankruptcy listed assets of €2 million and liabilities of €28 million.
It is a blow to Innate, which has one FDA-approved drug on the market, Lumoxiti (moxetumomab pasudotox-tdfk) for hairy cell leukemia. Innate paid AstraZeneca $50 million to license the U.S. and EU commercial rights to the drug.
The biotech also has a development deal with AstraZeneca for its leading pipeline candidate monalizumab, a midstage checkpoint inhibitor designed to block functions of NK and cytotoxic T cells. AstraZeneca paid Innate $170 million (€148 million) in 2018 to license the anti-NKG2A antibody and secure an option on five other prospects. The U.K. drugmaker also took a 9.8% stake in Innate Pharma. AstraZeneca’s former cancer head, Mondher Mahjoubi, is CEO of Innate.
Innate has reached similar deals with Novo Nordisk, Sanofi, Bristol-Myers Squibb and others.