Swept up into a coronavirus whirlwind, the biopharma industry has ramped up development of therapeutics and vaccines and altered business plans to fight the SARS-CoV-2 virus in a way that nobody could have imagined only months ago.
BioWorld began tracking these efforts in late February when there were 30 candidates in development and about 83,000 worldwide cases, according to the World Health Organization (WHO). The bulk of them – about 80,000 – were reported in China, where the virus originated in Wuhan. At that time, there were globally about 2,700 deaths from the virus.
Industry development more than doubled less than two weeks later. By March 6, a total of 71 therapeutics and vaccines were being studied by industry, government, nonprofits and academia. The virus had infected 95,333 globally across 85 nations and was responsible for 3,267 deaths.
As of March 23, there were 80 therapeutics, 45 vaccines and 75 diagnostics in development for COVID-19. WHO reported 332,935 confirmed cases and 14,510 deaths across 189 countries. By this time, borders were closing, travel restricted, schools and public offices and stores and restaurants shut down, and biopharma conferences, such as Bio-Europe Spring 2020, moved to virtual formats.
Only one month later, on April 28, the biopharma industry had 343 total candidates in development, including 249 therapeutics and 94 vaccines. Several of those companies began focusing on the respiratory complications that often lead to ventilator support or death. By that point, confirmed infections had climbed to 2.95 million and deaths had reached 202,597, according to WHO.
So what are the numbers as of the end of May? There are currently 318 therapeutics and 115 vaccines in development for COVID-19. Tracked diagnostics featured in BioWorld MedTech have reached 275, including antibody, antigen and molecular-based tests, of which 117 have emergency use authorization (EUA) from the FDA.
WHO now reports 6.06 million confirmed cases worldwide with a total of 371,166 deaths. The U.S. accounts for about 28% of the cases and deaths.
DAS-181, Actemra and Jakafi data upcoming
Of the 318 therapeutics in development, 21 have compassionate use or expanded access authorizations in the U.S. or other countries. Those with the U.S. FDA’s EUA include Gilead Sciences Inc.’s remdesivir, branded Veklury, and Sanofi SA’s chloroquine or hydroxychloroquine, branded Plaquenil. A generic version of remdesivir, Bemsivir, from Dhaka, Bangladesh-based Beximco Pharmaceuticals Ltd., was granted EUA in Bangladesh.
The later-stage candidates include seven in phase IV, 29 in phase III, 21 in phase II/III and 54 in phase II. Earlier candidates include three in phase I/II, 19 in phase I and 135 in preclinical studies, as well as 42 that are at the discovery phase.
Those with early signals of efficacy or extrapolated data from trials in other indications have received compassionate use, expanded access and emergency use authorizations somewhere across the globe. The latest stage candidates with one of those designations include:
- Algernon Pharmaceuticals Inc.’s NP-120 (ifenprodil), which is expected to begin a 462-patient open-label phase II/III study in July, with expected completion in January 2022.
- Ansun Biopharma Inc.’s DAS-181 (recombinant sialidase), which entered a phase III trial in May that includes a substudy in severe COVID-19 patients, with results a year away. A phase II/III in 82 patients has a primary completion date of June 30, 2020.
- Bellerophon Therapeutics Inc.’s Inopulse, which is entering a phase II trial with 30 patients in July. Primary completion is slated for January 2021.
- Genentech Inc.’s Actemra (tocilizumab), which is in several clinical trials, should have results following the June 30, 2020, completion of a phase III 300-patient study.
- Gilead Sciences Inc.’s Veklury (remdesivir) has already shown efficacy in late-stage clinical trials with more data arriving in the coming months. Most recently, its Simple phase III in moderate disease patients showed a five-day course led to a 65% clinical improvement in patients with moderate disease vs. those receiving standard of care alone. It has EUA in the U.S. and Japan.
- Humanigen Inc.’s lenzilumab entered a randomized, placebo-controlled phase III trial in 238 patients on April 30 with completion expected in September 2020.
- Incyte Corp.’s Jakafi (ruxolitinib) began a 402-patient phase III trial on May 1 with an estimated primary completion of July 10, 2020. Its Ruxcovid-Devent phase III trial with 500 patients is expected to complete July 29, 2020.
- La Jolla Pharmaceutical Co.’s Giapreza (angiotensin II) was expected to begin a 50-patient observational study on June 1 with completion estimated to be May 1, 2021. That trial follows an earlier observational study begun April 3 involving 100 patients with results expected following an October 2020 completion.
- Mesoblast Ltd.’s remestemcel-L entered a 300-patient phase III trial on April 30. The trial has an estimated primary completion of April 2021.
- Sanofi SA’s chloroquine or hydroxychloroquine (Plaquenil), both of which are in numerous late-stage clinical trials, have results expected as early as this summer. The FDA issued an EUA on March 28.
Near-term data for Ad5-nCoV and BNT-162
Of the 115 vaccines in development for COVID-19, 13 are in clinical trials, including two in phase II, three in phase I/II, and eight in phase I, leaving 101 that are in the preclinical and discovery stages. One potential vaccine, Innovation Pharmaceuticals Inc.’s brilacidin, is no longer being studied as a COVID-19 vaccine, but only as a therapeutic.
The most advanced vaccine candidates that are in phase II trials include Cansino Biologics Inc.’s Ad5-nCoV and Moderna Therapeutics Inc.’s mRNA-1273. While most clinical data are not expected until 2021, Cansino’s candidate and Biontech AG’s BNT-162, which is in a phase I/II, should have data readouts this year. To speed up development, several company will run multiple trials at different phases simultaneously.
A phase I trial of mRNA-1273 in 155 participants, which began March 16, is not expected to be completed until Nov. 22, 2021, but a phase II trial in 600 participants, which began May 25, should finish sooner in March 2021. Moderna announced May 29 that it was finalizing the protocol to begin a phase III study in July and has said a regulatory filing could come early in 2021. The company priced a $1.34 billion follow-on offering on May 19 to help fund worldwide manufacturing and distribution of the vaccine.
The earliest data for Cansino’s candidate could arrive in December 2020 from a phase I, 108-participant, study. Next up are results of a 508-participant phase II trial, to be completed in January 2021, and a 696-participant phase I/II trial in Canada, to be completed in March 2021.
Astrazeneca plc’s AZD-1222 (formerly ChAdOx1 nCoV-19) is in phase I/II, as is Biontech AG’s BNT-162. The AZD-1222 trial with 1,090 participants should complete in May 2021, while a phase II/III study with 10,260 participants is set to end in August 2021. A phase I/II dose-escalation trial evaluating four BNT-162 candidates in 200 participants should be done in just a few months, by August 2020, and a second phase I/II placebo-controlled, randomized trial with 7,600 participants is expected to be complete a year later.
Inovio Pharmaceuticals Inc.’s INO-4800 entered a year-long 40-volunteer phase I open-label study April 3, and the company has targeted a summer start for a phase II/III trial. Other potential vaccines in phase I trials include Novavax Inc.’s NVX-CoV2373, Shenzhen Geno-immune Medical Institutes’ aAPC vaccine, a vaccine from Sinovac Biotech Ltd. and Dynavax Technologies that uses the adjuvant CpG 1018, and Symvivo Corp.’s bacTRL-Spike vaccine.
A three-way partnership between Reithera Srl, Leukocare AG and Univercells SA aims to have their adenoviral vector vaccine in a phase I/II trial in June 2020. Other vaccines close to the clinic are Intellistem Technologies Inc.’s IPT-001, set to enter a phase I in September, and Sanofi SA and Glaxosmithkline plc’s adjuvanted recombinant subunit vaccine expected to enter phase I trials in the second half of 2020.
Grants, deals and clinical delays
Aside from the massive disruption that COVID-19 has created for drug development, it has also consumed many other areas of biopharma business efforts. A look at 2020 shows that 57% of the total grant money through April, about $870.9 million, has gone to those in the industry working on COVID-19 vaccines and therapeutics.
The Sanofi/GSK vaccine, for example, is supported by the U.S. Biomedical Advanced Research and Development Authority (BARDA), as are the vaccines developed by Moderna and Astrazeneca. Moderna received a commitment of up to $483 million in April from BARDA to develop mRNA-1273, while Astrazeneca is receiving up to $1.2 billion in BARDA funding through the Operation Warp Speed program.
A fourth candidate with BARDA support, from Johnson & Johnson’s Janssen Pharmaceuticals, received a $1 billion commitment for AdVac/PER.C6, its SARS-CoV2 recombinant adenoviral vector vaccine. It is expected to enter the clinic by September. Also receiving BARDA support are preclinical candidates from Merck & Co. Inc. and Sanofi Pasteur.
During April, 36% of collaborations between biopharma companies, valued at $13.5 billion, focused on the disease. An analysis of biopharma deals with academia, government and nonprofit entities indicate that more than 45% so far in 2020 are committed to fighting SARS-CoV-2. When looking at just April, the number jumps to 57%.
The pandemic has also dominated the clinical trial news with 45% in April the result of trial delays, suspensions and terminations and 12% focused on therapies and vaccines targeting the deadly infection. So far this year, BioWorld has tracked 408 clinical trials of therapeutics disrupted by COVID-19.
About a quarter of the regulatory data in April concerned global approvals for companies to begin testing various therapeutics or vaccines for COVID-19 and its complications. While the FDA has continued to issue action on non-COVID-19-related treatments on schedule, it issued guidance May 26 that it likely will be unable to sustain meeting all of its goal dates for new drugs and biologics.