The Phase III trials and pharma sales most likely to be disrupted by COVID-19
A look at pharma revenues and Phase III trials in China reveals who could be hit hardest by COVID-19
The coronavirus outbreak comes at a time when many major multinational pharmas are betting big on the China market for future growth. In an analysis of MNC revenues and dependence on trial sites in China, BioCentury zooms in on who is likely to be hit the hardest.
On the revenue front, AstraZeneca plc (LSE:AZN; NYSE:AZN) has by far the largest sales in -- and exposure to -- China. With 21% of the pharma’s 2019 product sales coming from China, the region is now its second-biggest, and fastest growing, revenue driver (see Figure: “Biopharma Revenues from China”).
In its earnings report Friday, AZ acknowledged that the COVID-19 (2019-nCoV) outbreak is likely to slow its China sales, at least for the next few months. The outbreak has exposed the fragility of the sales system in China, which is still heavily reliant on in-person hospital visits, and created an urgency to adopt digital tools (see “Coronavirus Disrupts MNC Operations in China”).
Figure: Pharma China sales
AstraZeneca plc (LSE:AZN; NYSE:AZN) has by far the most sales in China among multinational pharmas, at about $4.9 billion last year, and the largest exposure to China, with 21% of product sales coming from the country. The table includes MNCs that disclose China revenues, and revenue figures exclude non-drug sales.
To tap a bigger share of the China market, MNCs are increasingly incorporating China trials into their global development programs. Together, 21 MNCs are running a combined 224 global Phase III trials with sites in China (see Figure: "MNC Reliance on China for Global Phase III Trials").
The extent to which the COVID-19 outbreak will delay their Phase III plans outside China depends on how reliant the trials are overall on sites in China. In many cases, companies are including a relatively small number of China sites, enough to support filing in the country but not enough to derail plans elsewhere.
Other cases -- for example, where the percentage of trial sites in China crosses the 30% mark -- raise the question of whether the effects of the viral outbreak could extend beyond China.
Four MNCs have an average fraction of trial sites in China that exceeds 30% across all their ongoing global Phase III trials -- Amgen Inc. (NASDAQ:AMGN), Astellas Pharma Inc. (Tokyo:4503), Novo Nordisk A/S (CSE:NOVO B; NYSE:NVO) and Takeda Pharmaceutical Co. Ltd. (Tokyo:4502; NYSE:TAK).
Figure: MNC reliance on China for global Phase III trials
Together, 21 major multinational pharmas are sponsoring 224 global Phase III trials with sites in China that have not yet reached their primary completion dates, according to ClinicalTrials.gov. The ongoing COVID-19 outbreak could delay regulatory submissions in China for any of these programs. Whether delays in China could affect submissions elsewhere will depend on what fraction of the overall data come from sites in China. BioCentury analyzed the locations of the trial sites in each trial and determined the average percentage of sites in China for each company. At least four MNCs have an average fraction of trial sites in China that exceeds 30%. Source: ClinicalTrials.gov
In addition, at least nine MNCs are running multiple Phase III trials that are located only in China (see Table: “Ongoing MNC Phase III Trials Exclusively in China”).
All 29 of the trials in this category are testing therapies that are already approved outside China, and they reflect a mix of pharmas looking to gain a drug’s first approval in China or to expand its market to additional indications in the country.
Sanofi (Euronext:SAN; NASDAQ:SNY) tops the list with five ongoing China-only Phase III trials, followed by Roche (SIX:ROG; OTCQX:RHHBY) and Merck & Co. Inc. (NYSE:MRK) with four apiece.
Table: Ongoing MNC Phase III trials exclusively in China
At least nine multinational pharmas and biotechs are conducting multiple Phase III trials with sites exclusively in China that have not yet reached the last patient visit needed to measure the primary endpoint. All of these trials could see delays from the COVID-10 outbreak. About a third of those trials are expected to reach that last visit -- the trial's primary completion date -- in 1H20. The trials are a mix of new indications for products already available in China and potential first Chinese approvals for products approved elsewhere. Source: ClinicalTrials.gov
Another set of Phase III trials that will almost certainly face disruptions are China-only studies that were planned to start in the near future.
According to ClinicalTrials.gov, at least seven China-only Phase III trials were slated to kick off in 1Q20 (see Table: “Planned Phase III Trials in China”).
Three of the trials had already missed estimated start dates in January, before the COVID-19 outbreak began, and they aren’t likely to start now.
Four of the trials are from MNCs aiming to expand the market of therapies approved elsewhere, including Roche, which had planned to start a Phase III trial of Polivy polatuzumab vedotin to treat diffuse large B cell lymphoma (DLBCL) in Chinese patients. The antibody-drug conjugate (ADC) was approved in the U.S. in the indication last June, two months ahead of its PDUFA date.
The other three China-only Phase III trials with near-term start dates are from domestic biotechs whose therapies are not yet approved elsewhere.
Table: Planned Phase III trials in China
Seven Phase III trials with sites only in China have planned start dates in 1Q20, according to ClinicalTrials.gov. All are at risk of delay due to the ongoing COVID-19 outbreak. Four of the trials are sponsored by multinational pharma companies, and would support products approved elsewhere in the world, with two already approved in China for other indications. The other three trials are sponsored by Chinese companies, and they represent the most advanced trials of the products worldwide. Source: ClinicalTrials.gov
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