A stock image of coronavirus (123rf)
Following Celltrion’s monoclonal antibody treatment for COVID-19, a slew of homegrown therapies is on the way in the first half of 2021.
Chong Kun Dang Pharmaceutical is set to submit application for emergency approval in February, and GC Pharma in April. Under the fast-track review program for COVID-19 therapies and vaccines, the new submissions will hear back in 40 days from application.
Treatments are primarily for alleviating the condition in afflicted patients, rather than prevention.
Within the treatment bracket, the drugs are categorized according to how they are administered -- by injection or orally, for example -- and whether they are for people with mild symptoms or seriously ill patients relying on ventilators for breathing.
GC Pharma’s blood plasma-derived therapy for COVID-19, the GC5131A, is intended for more serious cases.
As the sole plasma therapy developer for COVID-19 in Korea, GC Pharma will apply for emergency approval of the GC5131A in April, as long as the results from its clinical 2a trial is successful. The 2a trial has tested GC5131A on 60 seriously ill elderly COVID-19 patients. GC Pharma says it will have the results analyzed within March.
GC5131A has helped a patient in his or her 70s reach full recovery at Kyungpook National University Chilgok Hospital in December. The drug has so far gained 38 therapeutic use approvals from the Drug Ministry upon requests from 16 hospitals. Each time an unapproved drug is used at a hospital, the medical professionals must request permission from the drug authority.
There is currently no open data to surmise the efficacy of GC5131A, as clinical tests preceding the 2a for the treatment were waived on grounds that drugs made using human plasma are naturally safe.
“Clinical phase 1 trials are designed to test the toxicity of a drug, and therefore unnecessary for plasma derivative drugs,” a GC Pharma official told The Korea Herald.
“The 2a trial will reveal the right amount of dosage for maximum efficacy,” the official said. “While we have produced the third batch of GC5131A using 240 liters of convalescent plasma, only after the 2a data analysis will we know how many people the drug can cover.”
With the third batch manufactured, GC5131A will be available for immediate use upon emergency approval. All GC5131A made using Korean blood plasma will be exhausted within Korea, the official said.
The drug will be free, following a pledge by GC Pharma CEO Huh Eun-chul to serve the greater good.
Overseas, where there are more seriously afflicted COVID-19 patients than in Korea, GC Pharma is involved in a phase 3 clinical trial of a separate plasma therapy developed by a global alliance comprising the world’s leading blood product manufacturers such as BPL, CSL, Takeda, Biotest and Octapharma.
GC Pharma’s role in the alliance will be to share the technical know-how and the supply of convalescent blood plasma pooled through GCAM, which operates GC’s blood plasma donation centers across the US.
While the GC Group sold GCAM to the North American business unit of Spain’s Grifols in October 2020, the company can still leverage GCAM facilities for another two years.
When asked if GC Pharma stands to gain financially from the involvement in the alliance, the GC Pharma official told The Korea Herald that “it is too early to discuss the details of the overseas commercialization plans.”
Since its founding in 1969, GC Pharma has focused on research and development of plasma derivatives. In 1971, it was the first Korean company to produce a blood plasma-based medicinal substance. Prior to COVID-19, the company’s main focus area had been rare diseases.
Other than the plasma treatment, there are preexisting drugs that are being repurposed as COVID-19 drugs.
Daewoong Pharmaceutical and Chong Kun Dang are each repurposing camostat and nafamostat, respectively.
Since the drugs are already been in use and their basic pharmaceutical safety guaranteed, it means companies can skip the phase 1 clinical trial designed to assess toxicity, giving them an edge in terms of development speed.
Chong Kun Dang’s nafamostat, approved in 2016, is traded under brand name Nafabeltan and is used to treat acute pancreatitis. It is also used as an anticoagulant. The drug is administered by injection and targets elderly COVID-19 patients with underlying diseases.
Chong Kun Dang has conducted clinical trials of nafamostat in Russia, where they have been able to find more COVID-19 patients than in Korea.
A Chong Kun Dang official told The Korea Herald that the company plans to apply for emergency use approval of nafamostat for the at-risk elderly cohort within February. Although the clinical tests were done overseas on foreign patients, the test design had been jointly devised with the Korean Drug Ministry, the official said.
“As long as the clinical data has credibility, there will be no dramatic hurdle in the process,” the official said.
So far, according to Chong Kun Dang, nafamostat has shown 2.9 times more efficacy than the standard therapeutic agents when tested on 100 moderate COVID-19 patients in a phase 2 trial in Russia.
Daewoong’s camostat has been in the market for a decade under the brand name Foistar to treat chronic pancreatitis and reflux esophagitis. Unlike other COVID-19 therapies, Foistar tablets have the advantage of easier administration as they come in the form of a swallowable tablet.
Daewoong has failed to derive statistically meaningful results from its 2a trial in Korea targeting 89 patients with either mild or no symptoms.
The company is conducting a larger phase 2b/3 trial to strengthen its data, as well as a separate phase 3 trial of camostat in combination with Gilead Sciences’ remdesivir.
Even so, all emergency approvals are conditional on a phase 3 trial.
Celltrion’s treatment, the leading homegrown COVID-19 therapy, had targeted COVID-19 patients with mild symptoms, but later showed efficacy for more serious cases.
Medical professionals in Korea are now testing the drug on serious patients.
Celltrion’s regdanvimab, or CT-P59, began and finished their review on Dec. 29 and Feb. 5 -- giving an indication of what the other players might have to expect in terms of timeline.
The company is currently undergoing talks with the US Food and Drug Administration and the European Medicines Agency since January for emergency approval overseas.
In the global phase 2 clinical trial, Celltrion consulted drug authorities in Korea, the US and Europe to fine-tune the design of the trial. A total of 327 candidates participated in the test of regdanvimab across Korea, Romania, Spain and the US.
In Korea, there were seven vaccines and 15 therapies targeted at treating COVID-19 being clinically tested, according to latest available data by the Ministry of Food and Drug Safety on Jan. 21. The 15 therapies comprised 13 substances.
Those in the final stage of a phase 3 clinical trial, are Celltrion’s regdanvimab, Lilly Korea’s baricitinib and MSD Korea’s MK-4482.
Those in the phase 2 trial, after which the companies may apply for conditional use approval, are Bukwang Pharm’s clevudine, Enzychem Lifesciences’ EC-18, Shin Poong Pharm’s pyronaridine-artesunate, Chong Kun Dang’s nafamostat, CrystalGenomics’ camostat, Daewoong Pharmaceutical’s camostat, GC Pharma’s GC5131A, Dongwha Pharm’s DW2008S and Immunemed’s hsVSF-V13.
Genexine’s GX-17 is in a phase 1b trial and NewGen Therapeutics’ nafamostat is in a phase 1 trial.
By Lim Jeong-yeo (firstname.lastname@example.org)