A trial participant treated with a single intravitreal injection of a high dose of the company’s ADVM-022 treatment has developed hypotony [clinically-relevant decrease in ocular pressure], with panuveitis [major inflammation of the eye] and loss of vision in the treated eye.
Following that discovery, Adverum said that, in the interests of patient safety, it had decided to immediately unmask the INFINITY Phase 2 study. The move would help it better understand the adverse event and to help identify and manage any similar potential risk to other patients in the trial, it remarked.
The California based gene therapy company is also conducting a thorough review of data from the ADVM-022 program and said it will report its findings as the analysis progresses.
Shares in Adverum went lower, seeing a drop of over just over 50% on Wednesday [April 28] following on from the news of the adverse event.
Laurent Fischer, Adverum’s CEO, said there will be ongoing monitoring of the patient in question and all patients treated with ADVM-022 as the company works with investigators, the data monitoring committee (DMC), the scientific advisory board, and healthcare authorities to thoroughly assess the case.
All clinical trial sites, as well as the US Food and Drug Administration (FDA), have been advised of this case, said the biotech.
The company said it is working closely with the DMC and the study sites to proactively develop additional recommendations for patient monitoring and management.
The INFINITY study is evaluating two doses of a single intravitreal (IVT) injection of ADVM-022 gene therapy, either a high dose 6 x 10^11 vg/eye or low dose 2 x 10^11 vg/eye. As of December 2020, the trial was fully enrolled, and all patients completed dosing of the single IVT injection of ADVM-022.
On top of those trial challenges, Adverum has been engaged in a proxy battle of late with a hedge fund that alleges governance failures and lack of oversight on the part of Adverum's board of directors.
Sonic, which is a 6.9% stockholder in the gene therapy company, has nominated three independent director candidates for election at the company's annual meeting, on May 12, stressing that Adverum needs gene therapy experts on its board; it claims the biotechnology company has “mismanaged” the scientific development process of of ADVM-022 to date.
Adverum, in response, said Sonic is looking to gain control of the board: its three proposed nominees, if elected, together with its two designees appointed in 2019, would constitute more than half of the board.
“Sonic’s nomination of three candidates for election to the board is not in the best interest of our stockholders – their election would diminish the diversity and the needed skills and experience represented on our board, and there is no reason to believe they would enhance our efforts to advance ADVM-022 toward commercialization and deliver global access to our vision-saving gene therapy.”
Gene therapy trials cleared to run again
Several gene therapy studies in the US have faced manufacturing and safety challenges in the past year and have been put on hold.
That said, the FDA, on Monday this week, gave the green light for a trial by Voyager Therapeutics to resume testing. The US regulator removed its clinical hold on the company’s Investigational New Drug (IND) application for VY-HTT01, a gene therapy candidate for the treatment of Huntington’s disease (HD), and confirmed that the company may proceed with its planned Phase 1/2 study.
The US agency had put the trial on hold because of issues with chemistry, manufacturing, and controls (CMC).
Similarly, this week, Netherlands based, uniQure, heard that its gene therapy clinical trial, which was paused late last year, has also been cleared to resume.
The US watchdog lifted the clinical hold on the company’s experimental gene therapy for hemophilia B - etranacogene dezaparvovec. The trial had been halted after a trial participant, who had received the therapy two years earlier, was diagnosed with a form of liver cancer. The pharma company announced, also on Monday, that the FDA agrees with its conclusion that the treatment was unlikely to have caused the volunteer's liver cancer.