LONDON – In the rush to test drugs against COVID-19, clinical trials in other indications are starting to be interrupted by the strains on health care systems and the fact that many potential patients are those most at risk from the effects of the novel coronavirus. The delays are set to have an impact on the financial health of biotechs with limited cash runways that now face longer waits for clinical trials to read out.
Addex Therapeutics SA announced it is postponing the registration study of its lead program dipraglurant in the treatment of levodopa-induced dyskinesia in Parkinson’s disease.
Similarly, Geneuro SA said it is delaying the start of a phase II trial of temelimab in multiple sclerosis, due to be held at the Karolinska Instituet, Stockholm.
Meanwhile, Synairgen plc has paused a phase II trial of SNG-001, an inhaled formulation of beta interferon, in the treatment of exacerbations of chronic obstructive pulmonary disorder (COPD), with 109 of 120 patients recruited. The trade-off is that the company is starting a 100-subject pilot study of the drug in COVID-19 patients who are hospitalized with respiratory symptoms.
In the U.S., New York-based Iveric Bio Inc. said it is delaying a second pivotal trial of Zimura (avacincaptad pegol) in the treatment of geographic atrophy, a complication of dry age-related macular degeneration. The 400-patient global study was due to start this month. The company said it needed to show “an abundance of caution” for the safety and well-being of the elderly patients who already have been pre-screened to take part.
On March 16, Provention Bio Inc. of Oldwick, N.J., announced a temporary hold on recruiting new patients to the phase III study of teplizumab in newly diagnosed type I diabetes. Patients currently on the study will complete treatment, and Provention said it remains on track to complete its rolling BLA submission for the anti-CD3 antibody before the end of 2020.
Tim Dyer, CEO of Geneva-based Addex said there “was not really a debate” about the decision to hold off starting the dipraglurant trial. “We were starting to review the situation about a month ago because we are very aware our patient population is a high-risk group. Then we were getting letters from sites that are ready to screen patients saying they had got central guidance and were no longer able to start studies.
“Groups at clinical sites with Parkinson’s disease patients are advising them to cancel non-urgent visits. You can’t then ask them to come in for pre-baseline [assessments],” Dyer told BioWorld.
While it is unclear how long the delay will be, Dyer pointed to China’s success in rapidly reducing the number of infections once it instituted strict control measures. Europe has now followed suit, with controls on travel, schools, universities, bars and restaurants closed, and people told to work from home.
“My personal feeling, assuming the China experience maps out, is we can talk about three months [delay],” said Dyer. Addex was due to present 2019 financial results on March 19, but has postponed until April 8, when Dyer said he thinks it will be possible to give investors a clearer picture of how long the trial will be held up.
Delays in starting trials will lead to delays in getting results, and Dyer said that will have a financial impact on Addex and other biotechs currently running clinical studies. “We have a base level of cash burn, even if we do nothing,” he said.
Jesus Martin-Garcia, CEO of Geneuro, agreed the COVID-19 crisis means there is no question about holding off on new trials. “The postponement is a logical and necessary decision to reduce the demands on health care professionals, prioritize treatment of COVID-19 patients and safeguard the well-being of multiple sclerosis patients,” he said.
“There are hospitals with tents in front, trying to triage patients; if you are not giving a critical treatment, it’s important not to flood them at this time,” Martin-Garcia said. “Our trial is important, but it is not as time critical as treating COVID-19,” he told BioWorld.
Geneuro, also based in Geneva, raised €17.5 million (US$18.9 million) in a private placing at the end of January and has sufficient cash until mid-2022. That is “well beyond” the end of the phase II trial, as long as the recruitment of 40 patients is completed in 2020.
Martin-Garcia also referred to the experience in controlling COVID-19 infections in China, and based on that expects a delay of six weeks or so. Also like Dyer, he is relieved not to have started the temelimab trial. “I’ve been hearing from a lot of colleagues in the industry who are in crisis management [over] ongoing trials. They are experiencing delays and drop-outs,” he said.
For Southampton, U.K.-based Synairgen, the switch from COPD to COVID-19 is a “sidestep,” said Richard Marsden, CEO.
The COPD trial and earlier studies in asthma have provided human data to indicate SNG-001 could be effective in treating serious respiratory symptoms of COVID-19. “At the simplest level, interferon-beta is like the conductor of an orchestra; it switches on viral defence pathways,” Marsden told BioWorld.
COPD, asthma and cystic fibrosis patients, as well as the elderly, are known to have a deficient interferon-beta response. “They don’t make enough, fast enough,” Marsden said. “When it is delivered directly to the lungs, we have shown it switches on [antiviral responses].”
That is demonstrated in the gene expression profiles of sputum samples taken 24 hours after administration of the drug.
A similar effect has been shown in vitro in the COVID-19-related coronaviruses that cause MERS and SARS. In addition, viruses, including coronaviruses, have evolved mechanisms which suppress endogenous interferon-beta production, helping them to evade the innate immune system.
Marsden praised the U.K. Medicines and Healthcare products Agency for its swift review of the SNG-001 COVID-19 trial, which is based on standardized study protocols prepared by the World Health Organization (WHO).
The blinded, placebo-controlled study will be run at an existing network of 10 leading centers in respiratory medicine set up by the National Institute of Health Research (NIHR).
Marsden said all the unknowns around COVID-19 make it particularly important this is a blinded, placebo-controlled trial. As yet there is no agreed standard of care. “In this setting, trying to interpret unblinded, open data is difficult,” he said.
The trial will treat patients who are hospitalized but not so severely affected they need mechanical ventilation. The endpoints will be based on the WHO-approved National Early Warning Score, a standardized way of assessing clinical deterioration in patients with acute illness, developed by the Royal College of Physicians in the U.K.
With cases on the rise in the U.K., Marsden said he is confident it will be possible to recruit 100 COVID-19 patients.
Synairgen is already “plugged in” to the NIHR clinical network, and as result, it has not been particularly expensive to set up the COVID-19 study. And although paused in the home straight, Marsden said he thinks it will be possible to complete the COPD trial.