DUBLIN – The global product development pipeline for COVID-19 is now twice as big as for any particular cancer indication, a major disease like Alzheimer’s or any other infectious disease indication.

David Thomas, vice president of industry research and policy, BIO

Since the virus sequence became available in January, 808 preclinical and clinical development programs have been initiated, David Thomas, vice president of industry research and policy for the Biotechnology Innovation Organization (BIO), said during a virtual Bio-Europe session on COVID-19 therapeutics. Small companies have been to the fore in populating that pipeline. “Seventy-three percent of these drugs originate in small companies. Even though the larger companies are, a lot of the time, driving the phase III trials, if you dig deep enough, they are actually originating from small companies.” Fifty-two percent of the programs originate in the U.S. China comes next with 6%, while Germany, the U.K. and Switzerland are also active.

According to BIO’s pipeline tracker, the projects comprise 25% vaccines, 27% antiviral drugs – which target viral or host proteins involved in the life cycle of the virus – and 48% treatments directed at host responses to the virus, which include anti-inflammatories, anti-coagulants and immunostimulatory molecules, such as interferons. The latter category – which accounts for almost half of the total pipeline – is large because most of its constituent programs existed prior to the emergence of SARS-CoV-2.

Richard Marsden, CEO, Synairgen

“Ninety percent of it came from either approved drugs or what we call redirected projects that were already ongoing,” Thomas said. “The industry was able to pivot very quickly to the pandemic, because we had an ecosystem in place that was working and a lot of technologies that had been developed over many years.” The vaccine pipeline is, unsurprisingly, mostly novel – 95% of the projects are new, whereas just 5% are either repurposed products or redirected programs. The antiviral category includes a mix of the old and the new – 26% of the programs are repurposed, 14% are redirected and 60% – the bulk of them antibody programs – are novel.

Of the 808 programs BIO has identified, 762 are still in active development, said Thomas, while 25 are inactive, 11 have failed (seven antivirals and four treatments), while 10 programs have gained regulatory approval in at least one jurisdiction. The latter group includes a nitric oxide device, convalescent plasma and Gilead Sciences Inc.’s antiviral drug, Veklury (remdesivir), in the U.S., as well as dexamethasone in the U.K., still the only drug to have demonstrated a survival benefit in a controlled clinical trial, and two adenoviral vaccines, which are technically in phase III but have been authorized in India and Russia, respectively, for dosing in certain populations.

At this point, just over 300 programs have entered clinical development, including 45 antivirals, 45 vaccines and 214 treatments. The latter category is extraordinarily crowded. “There is a lot of competition for enrollment when you have so many drugs going after the same indication in late-stage COVID,” Thomas said.

Gregg Szabo, vice president and commercial leader immunology/virology, Merck

Speaking during the same session, Richard Marsden, CEO of Southampton, U.K.-based Synairgen plc, identified a role for governments in tackling this problem. “If you’re just embarking on phase II trials now, you’re going to struggle to find sites and find patients,” he said. “A tricky thing that governments might have to do is kind of ration where drugs can get assessed in different trial sites.” The U.K. government is conferring urgent public health research status on select programs, which offers a kind of fast-lane to the most promising programs. Synairgen’s inhaled formulation of interferon-beta, SNG-001, recently received that designation. “Without it, you’d have to walk past the U.K., because you’re not going to get many people recruited into your clinical trial.” It’s a necessary intervention, given the urgent need to generate high-quality clinical data as quickly as possible. “Otherwise, everyone is going to end up with 50 or 60 patients in their trials, and we’ll all be scratching our heads trying to work out what worked and what didn’t work.”

Governments and supranational organizations also have an important role in supporting the establishment of streamlined regulatory processes, said Gregg Szabo, vice president and commercial leader immunology/virology at Merck & Co. Inc., of Kenilworth N.J. (known as Merck Sharpe & Dohme (MSD) in Europe.

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“Even for a large company like MSD, it’s daunting if we look around the world at the number of countries and all the different regulatory authorities,” he said. The company is moving an oral antiviral, molnupiravir (formerly MK-4482, EIDD-2801), into pivotal phase II/III studies in both hospital and outpatient settings. It is already grappling with the problem of global distribution, in the event that they are successful.

“Our principle is to have this product available not based on socioeconomic status but really based on medical need,” Szabo said. Filing multiple applications in different jurisdictions would introduce considerable delays. He proposed a “reliance pathway,” through which countries with less well-developed regulatory bodies could refer to sophisticated regulatory authorities such as the FDA or the EMA in their decision-making processes. “Without something like that formally in place, and countries buying into it, we’re going to be hamstrung in effectively getting the product out quickly,” he said.

Neil Mulcock, vice president, government affairs, EMEA, Gilead Sciences

The urgency of the crisis has engendered close cooperation between developers and regulators in terms of rapid turnaround times for IND filings and expedited approval pathways for promising therapies. “It’s truly been impressive how collaborative the regulators have been in this pandemic, and I’d like to see that continue” said Kylie O’Keefe, vice president and head of global strategic marketing and business intelligence at Plainfield, N.J.-based PTC Therapeutics Inc. “The ability to collaborate with the same shared end goal for success has been truly impressive and I’d like to see that continue.”

Although it is, of course, far from over, the pandemic has also demonstrated how constructively drug developers can work with governments, said Neil Mulcock, vice president, government affairs, EMEA, at Foster City, Calif.-based Gilead. “This pandemic has provided our industry with an opportunity to show to them how strategically important we are – and actually what we are all about is advancing the health of individuals and protecting the public health and well-being of the population,” he said. “If we can hang onto that, as we progress post-pandemic, that will be a wonderful thing.”

The conference closed Oct. 29. Bio-Europe Spring 2021 will be delivered digitally from March 22 through March 25.

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