More than two million doses of Medigen’s MVC-COV1901 have been administered domestically, but it has yet to gain traction internationally. Meanwhile UBI Pharma’s UB-612 is pending emergency-use authorization in Taiwan.
Early in the coronavirus pandemic, Taiwan made a fateful decision: It would develop its own COVID-19 vaccines and make them a key part of its inoculation effort. Two local biotech firms, Medigen Vaccine Biologics Corp. and UBI Pharma, took on the task.
The Tsai Ing-wen administration had sound reasons for wanting domestic COVID-19 vaccines. Since it is not a member of the World Health Organization (WHO), Taiwan could not count on being able to expeditiously secure vaccines from international producers through the WHO’s COVAX program. Possible interference by China, which has blocked Taiwan from obtaining WHO membership or even observership, loomed large. Having some self-sufficiency to inoculate the population against SARS-CoV-2 seemed prudent from a public health standpoint.
Further, if local firms could develop their own COVID-19 vaccines, it would boost the biotech sector – one of the strategic industries targeted by the Tsai administration in its 5+2 Industrial Innovation plan – and possibly open up new international markets for Taiwanese biotech. It was clear from the onset of the pandemic that developing countries would face a vaccine shortfall, and Taiwan saw a chance to be a vaccine supplier to some of them.
“It is worthwhile for Taiwan to maintain its own capacity [to produce COVID-19 vaccines] as it has the R&D and manufacturing capability, and there has been a vaccine shortage in many countries,” says Wallace Lin, secretary general of the Taiwan Bio Industry Organization, an NGO that promotes Taiwan’s biotech industry.
Yet as it turns out, developing a vaccine for a novel pathogen like SARS-CoV-2 is perhaps more challenging than the Taiwanese government or local biotech firms envisioned. Thus far, only Medigen has received emergency approval authorization (EUA) for its vaccine, MVC-COV1901. UBI Pharma’s application was rejected last August after its UB-612 COVID-19 vaccine candidate failed in one aspect to meet the standards set by the Taiwan Food and Drug Administration (TFDA). Despite UBI Pharma reapplying for the EUA in March, the TFDA has not signaled that approval is forthcoming.
“It definitely will be helpful for Taiwan to have its own COVID-19 vaccines, but because the government was too eager to launch them, some of the required scientific processes were not really well established,” says one doctor and veteran of Taiwan’s healthcare industry, who requested anonymity due to the sensitivity of the matter.
The doctor notes that Medigen’s vaccine was launched during Taiwan’s first domestic COVID-19 outbreak last July, when the country’s vaccination rate was just 20%. Confident that its strict border controls could contain the virus, the government had not aggressively procured vaccines from global producers, the doctor says. Meanwhile, the ever-mutating virus caused global demand for vaccines to surge, with production often unable to keep up. Thus, when cases in Taiwan began spiking last year, the only way to boost the vaccine supply quickly was to launch the domestic vaccine.
As of April, just two countries besides Taiwan have granted an EUA to Medigen’s vaccine: Paraguay and Somaliland. The main reason it has not been greenlighted elsewhere is that Medigen has not yet completed Phase III clinical trials of the vaccine, and it thus lacks WHO approval. In a bid to bring its vaccine to market faster amid Taiwan’s COVID-19 outbreak last year, Medigen opted for immunobridging, a controlled trial used in the place of efficacy data. Immunobridging studies seek to infer the likeliness of vaccine protection by comparing the immune response (neutralizing antibodies) the vaccine candidate creates in the body to that elicited by existing WHO-approved vaccines.
Though regulatory authorities in the EU, Switzerland, UK, Australia, Canada, and Singapore have deemed immunobridging studies acceptable for authorizing COVID-19 vaccines, the technique is not yet considered equivalent to clinical trials. Indeed, placebo-controlled disease endpoint trials remain the gold standard for vaccine authorization.
“From the beginning, Medigen did not follow a standard internationally recognized procedure so it is really hard to judge the efficacy of this vaccine,” says Dr. Chan Chang-chuan, an epidemiologist at National Taiwan University’s College of Public Health. To accurately assess the vaccine’s ability to prevent disease in controlled circumstances, “we need to have more human subjects – 30,000 to 50,000 is standard in a Phase III trial.”
The major international producers of COVID-19 vaccines have followed those guidelines. Moderna’s Phase III trial enrolled 30,000 subjects, AstraZeneca about 32,500, and Pfizer-BioNTech more than 43,000.
Adding to Medigen’s challenge is the limited data comparing the performance of its vaccine to others in the real world. “We need this kind of real-world data to prove that Taiwan’s domestic vaccines are effective,” Chan says.
To date, while no large-scale studies of the effectiveness of Medigen’s vaccine have been completed, there have been some smaller ones. Citing a trial of 200 participants carried out by Taoyuan General Hospital, Medigen in January reported higher neutralizing antibody levels in people who were given its COVID-19 vaccine as a booster after receiving two AstraZeneca doses, similar to the antibody levels in those who received an mRNA vaccine booster.
Medigen also cites Ministry of Health and Welfare (MOHW) data announced in April showing that compared to other vaccines, MVC-COV1901 can better protect against so-called “breakthrough infections,” in which a fully vaccinated person becomes infected with COVID-19. Based on the last dose of each type of vaccine, the MVC vaccine had a breakthrough infection rate of 2.6 per 100,000 vaccinees, compared to 10.2 for AstraZeneca’s Vaxevria, 7.5 for Pfizer-BioNTech’s Comirnaty, and 6.5 for Moderna’s Spikevax.
Despite the obstacles MVC-COV1901 faces, it may have opportunities in niche markets, notably in developing countries. Just 16% of people in low-income countries had received at least one vaccine dose as of April, according to The New York Times. In Africa, just 20% of people have received at least one dose.
In response to a question from Taiwan Business TOPICS about whether the company sought to distribute its vaccine in Latin America, Southeast Asia, and Africa, Medigen vice chairman and CEO Charles Chen said that those territories “are high on our priority list, but we have to go through the regulatory processes and scrutiny prior to being able to sell.”
In December 2021, Somaliland became the second country after Taiwan to grant an EUA to Medigen’s vaccine after Taiwan announced it would donate 150,000 doses to the de facto African state that declared independence from Somalia in 1991. Somaliland maintains offices in about a dozen countries but does not have diplomatic ties with any nation.
This effort appeared to have political as well as public health considerations given Taiwan’s dwindling number of diplomatic allies – down to 14 after Nicaragua severed relations earlier this year – and Somaliland’s lack of ties with China. In February 2020, Taiwan and Somaliland signed an agreement to establish reciprocal representative offices, which they did later that year.
Vaccine diplomacy may also figure into Medigen’s presence in Paraguay, Taiwan’s last remaining diplomatic ally in South America. Paraguay experienced a surge in COVID-19 cases last spring. That April, Taiwan accused China of offering Chinese vaccines to Paraguay in exchange for its breaking ties with Taipei. Paraguay’s foreign ministry said in a statement that brokers claiming to offer Chinese COVID-19 vaccines approached them with such a deal, but could not confirm their links with the Chinese government. Paraguay ultimately rejected the conditions.
In February, Paraguay became the third country to grant an EUA to Medigen’s vaccine following completion of a Phase III trial of 934 people that compared the Taiwanese firm’s vaccine with AstraZeneca’s. According to Medigen, MVC-COV1901 generated 3.7 times as many neutralizing antibodies as Vaxevria, meeting the standard for “superiority.”
Medigen is also conducting Phase III trials in the Philippines, Colombia, and Mali under the WHO’s Solidarity Trial Vaccines program. WHO has described the program as an “international, randomized clinical trial platform designed to rapidly evaluate the efficacy and safety of promising new candidate vaccines selected by an independent vaccine prioritization advisory group composed of leading scientists and experts.”
Should Medigen’s vaccine perform well in Solidarity Trial Vaccines, it could potentially make deeper inroads in the developing world. While Colombia has fully vaccinated 69% of its population and the Philippines 61%, Mali’s vaccination rate is just 5%. Additionally, the Philippines and Colombia still need to administer many more boosters. Their booster rates are 11% and 21%, respectively.
In the long run, receiving WHO authorization will be paramount for Medigen’s global prospects as without it, those vaccinated with MVC-COV1901 will face similar travel restrictions as the unvaccinated. To be sure, Taiwan can negotiate recognition of the vaccine on a per-country basis, but the process is arduous. Thus far, just five nations recognize Medigen: New Zealand, Palau, Indonesia, Belize, and Thailand.
Nevertheless, Medigen’s vaccine enjoys relatively high acceptance in Taiwan. For Taiwanese who rarely travel abroad, its lack of international recognition is not a major issue. Further, it has received the endorsement of President Tsai Ing-wen and Vice President William Lai, both of whom chose it over international brands.
Medigen’s status as a protein subunit vaccine might be a benefit for people especially concerned about vaccine side effects, such as Taiwan’s elderly, the segment of the population with the lowest vaccination rate. “Since protein subunit vaccines have been in use for more than 20 years, related safety concerns are fairly well understood,” says Johnsee Lee, honorary chairman of the Taiwan Bio Industry Organization. In contrast, “third-generation mRNA vaccines have only existed for a couple of years, and so we do not know as much about their long-term effects.”
Medigen’s Chen notes that the company’s COVID-19 subunit vaccine has three components: the spike protein licensed from the U.S. National Institute of Health; aluminum hydroxide, which has been used in vaccines for decades; and the adjuvant CpG 1018 supplied by the U.S. firm Dynavax, approved by the U.S. FDA for use in a Hepatitis B vaccine. “Formulated, this makes for a vaccine that drives a strong immune response with lesser amplitude of side effects compared to the established mRNA vaccines,” he says.
Production hub prospects
Several sources who spoke to TOPICS for this report urged Taiwan to focus on becoming a production hub for global COVID-19 vaccine brands. They noted that Taiwan has decades of experience serving as a contract electronics maker for the world’s largest technology companies and enjoys a reputation for manufacturing prowess. They also expressed concern that smaller biotech firms could not viably compete with multinational pharmaceutical giants.
“Latecomers from Korea, Japan, and Singapore are all developing some kind of vaccine and they are facing the same kind of obstacles as the Taiwanese companies,” says NTU’s Chan. While he believes the intention to have a domestically produced vaccine is correct, the competitive environment favors the biggest and best-capitalized firms. Moderna has a market capitalization of US$56.9 billion, AstraZeneca US$159.6 billion, Pfizer US$275.4 billion, and BioNTech US$37.2 billion. In the race to launch COVID-19 vaccines, those firms not only could draw on their own vast resources, but they also received significant financial support from the U.S. (Moderna and Pfizer), UK (AstraZeneca), and German governments (BioNTech).
That was not the case for Taiwan’s two COVID-19 vaccine producers. Though it encouraged domestic vaccine production, the Taiwanese government did not commit massive state funding to the endeavor. With limited money to spend – Medigen has a market capitalization of US$1.96 billion and UBI Pharma US$266.8 million – local firms faced limitations that the global vaccine makers did not.
“The game was almost over in 2020,” Chan says. “There were some clear winners, and it’s very hard to catch up.”
The question now is whether Taiwan may have also fallen behind in the race to become a manufacturing base for COVID-19 vaccines. Its strongest competitor is South Korea, which in August 2021 announced a US$2 billion plan to emerge as a global COVID-19 vaccine production hub by 2025. Since May 2021, South Korea’s Samsung Biologics Co. has been assigned the task of “fill and finish” – filling vials with the vaccine and finishing the process of packaging the product for distribution – for Moderna’s Spikevax. In December 2021, the Ministry of Food and Drug Safety of Korea issued a marketing authorization to Moderna Korea that officially allows Spikevax manufactured at Samsung Biologics’ local pharmaceutical production facilities to be distributed domestically and exported.
The doctor and healthcare industry veteran who spoke to TOPICS anonymously urges Taiwan to not miss this opportunity. “Korea is already two to three years ahead of Taiwan in this race,” he says. “They got the distribution rights for some great vaccines. They are aggressive – not just the entrepreneurs, but also the government.” In contrast, “the Taiwanese government is always doing things in a very conservative way, afraid the public will oppose them.”
Taiwan has established an agreement with Moderna that will see the U.S. biotech firm set up a subsidiary here to support delivery of its vaccines and therapeutics. Moderna plans to do the same in Hong Kong, Malaysia, and Singapore. Moderna, which is known to be highly protective of its mRNA technology, has yet to say if it will establish a production hub in Taiwan.
Ultimately, whether Taiwan focuses on producing its own vaccines or serving as a contract manufacturer for global brands, it must be aware that mRNA vaccines are likely to be the wave of the future, Chan says. “Are we going to keep promoting vaccines using old technology or those with newer technology? It’s like analog and digital,” he says. While analog technology continues to have specific applications, “the world has gone digital.”