SINGAPORE: A potential COVID-19 antibody drug developed by a Singapore-based company will be tested on 1,305 infected patients locally and abroad, in what would be its final trial before it can be approved for treatment in Singapore.
The biotechnology firm Tychan said on Friday (Dec 11) that it had received approval from the Health Sciences Authority (HSA) in October to begin Phase 3 of the clinical trial for its monoclonal antibody called TY027.
The antibody could slow down the progression of COVID-19 in patients, help them recover faster, and provide temporary protection against the coronavirus.
During the Phase 3 trial, researchers will administer the drug directly in the blood of volunteer patients who are in the early stages of the disease and assess whether it can stop them from deteriorating any further.
For instance, the drug will be deemed effective if a patient has a fever at the start of the trial and does not develop more severe symptoms by the end.
“If the antibody is proven efficacious in this trial, it will be submitted for review by HSA and other regulatory agencies as a new drug,” Tychan said, adding that the company is trying to ensure Singapore gets the drug as soon as possible.
IS IT SAFE?
The announcement comes after Tychan announced in June that it will start Phase 1 of the trial in healthy volunteers. The firm said on Friday that these early trials showed “no serious adverse events”, as it evaluated dosages of up to 30mg/kg.
“Studies supporting the new drug application, including chemistry, manufacturing, and control, and the Phase 1 trials were completed thoroughly and safely,” it said.
The drug was “so safe” that researchers increased the dose from 20mg/kg to 30mg/kg to account for heavier patients and give the best chance of eliciting a quick antiviral effect, said Tychan co-founder Professor Ooi Eng Eong.
“So far we have not seen any side effects that would be of concern. In fact, most of them don’t even show any side effect at all. So it looks to be very safe.”
The length of the trial will depend on how quickly researchers can recruit the more than 1,300 patients, who have to be in the first six days of their illness.
“That’s the point where there’s the virus in the airway, and this antibody is attacking the virus,” said Prof Ooi, who also works at the Duke-National University of Singapore Medical School.
“So if the virus is not around anymore, there’s really no point to treat.”
TRIAL PARTICIPANTS FROM SINGAPORE AND ABROAD
Recruitment for the trial will begin on Friday and involve patients from partner hospitals - Singapore General Hospital and National University Hospital. Suitable patients from Changi General Hospital and Sengkang General Hospital can also be referred to the trial.
Given Singapore’s low incidence of COVID-19, Tychan said the trial will also be conducted in partner hospitals overseas, such as the Sheba Medical Centre in Israel.
Tychan is also exploring collaborations with medical facilities in other countries that manage coronavirus cases in a similar way as Singapore - where potential COVID-19 patients are detected and tested early.
Prof Ooi declined to name the other countries Tychan is in discussion with, citing non-disclosure agreements.
“There were some countries that we spoke to which basically said there is no way they can recruit patients within the first six days because their system is just so overwhelmed,” he said.
“Usually the patients show up about 10 days or more after the onset (of the illness). We also realised that countries which had the technology to do these trials were so overwhelmed with managing severe cases, that they could not do the trial.”
ANTIBODY VERSUS VACCINE
Prof Ooi had previously said that the drug could be potentially used in many ways.
This includes preserving COVID-19 patients’ respiratory function or weaning them off ventilators, and as temporary protection for healthcare workers or those who travel to COVID-19 hotspots.
While Prof Ooi acknowledged that vaccines will give longer protection than Tychan’s drug, he said vaccines might not be suitable for everyone, including those who are on anti-cancer or auto-immune therapy, as well as those with a history of allergies.
“The other thing we don't know about the vaccine at this stage is whether it will stop infection,” he added.
“What we do know is that it can stop disease. Therefore, a person who is vaccinated could become infected and continue to pass the virus on. So therefore to protect the population, we do need both.”
In the US, the Food and Drug Administration has granted emergency use authorisation for two monoclonal antibody drugs to treat mild to moderate COVID-19 patients who have a higher risk of developing serious illness.
Unlike the two US antibodies which are derived from infected humans or animals, Prof Ooi said Tychan’s version was “made entirely by engineering”. By design, this allows the antibody to target crucial parts of the virus.
“Think of it like a house. You can renovate the house, but you cannot remove the pillars because the whole thing will crumble. So, we went after the pillars of the virus so that the chance of mutation is very, very small,” he added.
“We are confident that our antibody has minimal chance of developing resistance. But obviously as in all that we have learnt about antimicrobial resistance, you can never, never have just one drug.”
DELAYS AND CHALLENGES
Still as with any clinical trial, “there is always a chance” that Tychan’s trial might not be able to recruit enough volunteers, Prof Ooi said.
Phase 3 was supposed to start in August but researchers decided to hold back as there were very few COVID-19 patients in Singapore, he explained.
For safety purposes, patients who have poorly controlled diabetes or unstable heart disease will be excluded from the trial.
“We cannot force the patient to take the drug,” Prof Ooi said. “It is through informed consent. For us, to de-risk means we have to keep finding new partners.”
Recruiting patients in other countries will also take some time as Tychan will need to get approval from health regulators in those countries as well as an ethics board, he said.
“Multi-country trials are much harder to manage because we really have to be sure that the protocol is adhered to, there’s compliance, quality control and all the checks are done,” he added.
“For Tychan being such a small company, to do a Phase 3 in different countries is extremely challenging. That’s one of the considerations that ... led to us shifting the timeline from August till now.”
Nevertheless, Prof Ooi said Tychan is already in the process of finalising details on the mass manufacturing of its drug, highlighting that the technology of producing antibodies is “a lot more mature” than that used to produce COVID-19 vaccines.
Monoclonal antibodies can be isolated and manufactured in large quantities to treat diseases.
When asked if TY027 will be manufactured in Singapore, Prof Ooi said the company has explored various options including producing it locally.
”I can’t release details now because these are business transactions that are ongoing,” he said. “But we are definitely looking at all the possibilities that would give Singapore the best chance of having the drug as soon as possible.”
Studies for the development of TY027 were completed in less than four months due to “breakthrough thinking and innovation”, Tychan said. Such developments typically take 12 to 18 months.
“We are hopeful that TY027 will pass the Phase 3 clinical trial and be deployed as soon as possible to mitigate the adverse impact brought by COVID-19,” Prof Ooi said.