Top 35 treatments in development against Coronavirus disease 2019 (COVID-19)
Treatment: Kaletra® (also marketed as Aluvia; lopinavir/ritonavir)
Type: HIV-1 protease inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and children 14 days old and older.
Status: China’s National Health Commission authorized Kaletra to treat pneumonia caused by SARS-CoV-2, AbbVie announced on January 27. AbbVie has donated RMB 10 million ($1.4 million) of Kaletra to Chinese authorities “as an experimental option to support this growing public health crisis.”
The Health Commission of Henan Province announced January 31 that three confirmed cases of patients diagnosed with new coronavirus infections recovered after taking Kaletra, a combination of ritonavir and lopinavir. As of that date, nucleic acid testing of more than 20 confirmed cases of patients infected with new coronavirus, admitted to hospitals in Zhejiang Province turned negative after taking Kaletra, according to Ascletis Pharma, which is evaluating a combination therapy of its own candidates ASC09 and ritonavir (See below).
Treatment: Ampligen® (rintatolimod)
Type: Immune modulator indicated for severe chronic fatigue syndrome
Status: AIM ImmunoTech said February 27 it is partnering with ChinaGoAbroad, a matchmaking and advisory service for cross-border deals involving China, to facilitate talks with China’s government to allow entry of AIM’s drug candidate Ampligen into China for use as a prophylactic/early-onset therapeutic against COVID-19. The companies are pursuing approval for trials in China, and FDA authorization under regulations allowing the export of investigational drugs for use in a sudden and immediate national emergency. Through those rules, AIM won FDA authorization to import Ampligen into Argentina in 2019 as a treatment for severe chronic fatigue syndrome.
Treatment: Single-dose, intranasal vaccine designed to provide systemic immunity
Type: Vaccine based on Altimmune’s proprietary platform vaccine technology, which the company applied in developing NasoVAX, the company’s influenza vaccine candidate that showed positive Phase IIa results.
Status: Altimmune said February 28 that it completed the design and synthesis of the vaccine, and was advancing it toward animal testing and manufacturing. Clinical testing of the vaccine could start as early as August. The company also said it was “actively engaged in discussions with a number of potential partners.”
Type: Recombinant human angiotensin-converting enzyme 2 (rhACE2) developed for the treatment of acute lung injury, acute respiratory distress syndrome, and pulmonary arterial hypertension.
Status: Vienna-based APEIRON on February 26 launched a pilot investigator-initiated clinical trial in China designed to assess APN01 as a treatment for patients with severe SARS-CoV-2 infection. The randomized, unblinded trial will treat 24 patients for seven days to obtain preliminary data on the impact of rhACE2 on biological, physiologic, and clinical outcomes, as well as safety. Suzhou-based Angalpharma is coordinating the Chinese clinical trial, with support from dMed Pharmaceutical, a CRO based in Shanghai.
Treatments: Ganovo® (danoprevir) plus ritonavir; ASC09 and ritonavir; ASC09 and oseltamivir; ritonavir and oseltamivir;
Types: HIV protease inhibitors
Status: Ascletis stated February 26 that three COVID-19 patients treated with its combination therapy Ganovo® (danoprevir) plus ritonavir were discharged from the Ninth Hospital of Nanchang following treatment. On February 2, Ascletis said it is actively assisting “relevant medical institutions and medical researchers” in clinical trials assessing the combination of Ascletis’ ASC09 and ritonavir for COVID-19, following a request they made to the company. On January 25, Ascletis applied to the National Medical Products Administration and its Drug Evaluation Center to include ritonavir and ASC09 fixed-dose combination into the national emergency channel.
China’s Tongji Hospital is also testing combinations of ASC09 and Tamiflu (oseltamivir), ritonavir and Tamiflu (oseltamivir), and Tamiflu alone in one trial listed on ClinicalTrials.gov (NCT04261270). Tamiflu is distributed in the U.S. by Genentech, a member of the Roche Group, under license from Gilead Sciences. Also, a trial prospectively registered by The First Affiliated Hospital of Zhejiang University School of Medicine is assessing combinations of ASC09 and ritonavir, and lopinavir and ritonavir (ChiCTR2000029603).
Bayer and numerous Chinese manufacturers
Treatment: Chloroquine phosphate (marketed by Bayer as Resochin®)
Type: Phosphate salt of chloroquine, a quinoline compound with antimalarial and anti-inflammatory properties. Resochin was discovered by Bayer and introduced into clinical practice in 1947 to treat malaria.
Status: Evaluated in clinical trials in over 10 hospitals in Beijing, as well as in south China’s Guangdong Province and central China’s Hunan Province, where it has “shown fairly good efficacy” according to Sun Yanrong, deputy head of the China National Center for Biotechnology Development under the Ministry of Science and Technology (MOST), the state-owned Xinhua news agency reported on February 17. Chloroquine and remdesivir were “highly effective in the control of 2019-nCoV infection in vitro,” a team of Chinese researchers reported in a study published February 4 in Cell Research. After China’s National Health Commission included chloroquine phosphate in its latest treatment guidelines for COVID-19 pneumonia, eight Chinese companies sped up manufacturing and supply of the drug, Shanghai Daily reported February 20.
Beijing Staidson Biopharma and InflaRx
Type: Anti-C5a monoclonal antibody in development for COVID-19 as well as hidradenitis suppurativa
Status: Chinese authorities approved clinical trials of IFX-1 as a COVID-19 treatment in February.
Treatment: Galidesivir (BCX4430)
Type: Nucleoside RNA polymerase inhibitor designed to disrupt the viral replication process
Status: Shown broad-spectrum activity in vitro against more than 20 RNA viruses in coronaviruses and viral disease families that include filoviruses, togaviruses, bunyaviruses, arenaviruses, paramyxoviruses, and flaviviruses.
Type: Anti-necrosis drug whose glyco-polymer structure consists of hybrid molecules integrating the Hemoglobin molecule and a proprietary polymer chemical structure. BXT-25 is company’s lead product candidate, designed to carry oxygen to tissues when the flow of blood is blocked.
Status: Boston-based Bioxytran said February 5 that it is exploring partnering with “international drug companies” to develop BXT-25 as a treatment for Acute Respiratory Distress Syndrome (ARDS) in end-stage patients with SARS-CoV-2. Since BXT-25 is 5,000 times smaller than red blood cells, the company will use MDX Life Sciences’ MDX Viewer to assess the safety and efficacy of the drug.
Celularity and Sorrento Therapeutics
Type: Allogeneic, off-the-shelf, placental-derived Natural Killer (NK) cell therapy
Status: The companies on January 30 launched a clinical and manufacturing collaboration designed to expand the therapeutic use of Celularity’s CYNK-001 to COVID-19. Sorrento and Celularity agreed to assess CYNK-001 as a potential novel therapy for coronaviruses, specifically SARS-CoV-2. Sorrento—which owns 25% of Celularity—agreed to use current existing capacity in its cGMP cell therapy manufacturing facilities in San Diego to supplement Celularity’s new cGMP facility in Florham Park, NJ. Sorrento said it is already in contact with “leading” scientists and local Chinese experts to discuss clinical validation and logistics requirements for fast-tracking CYNK-001 in China.
Chugai Pharmaceutical and Zhejiang Hisun Pharmaceutical
Type: Humanized mAb targeting interleukin-6
Status: A 94-patient trial assessing Tocilizumab has been registered with Chinese authorities by The First Affiliated Hospital of University of science and technology of China (Anhui Provincial Hospital) (ChiCTR2000029765).
CSL and The University of Queensland
Type: Unspecified vaccine based on subsidiary Seqirus’ proprietary adjuvant technology, MF59®
Status: On February 12, CSL said it will provide technical expertise and a donation of MF59 to the University of Queensland’s preclinical development program. The University will use the adjuvant to test the viral protein it is developing with its molecular clamp technology, CSL said. The company also committed a donation of RMB 1 million ($143,000) to the China Red Cross toward efforts to combat the epidemic.
Treatment: mRNA-based vaccine
Type: Vaccine applying CureVac’s mRNA vaccine development platform
Status: CureVac and the public-private Coalition for Epidemic Preparedness Innovations (CEPI) are collaborating to develop a vaccine against SARS-CoV-2, the partners said January 31, extending their existing partnership to develop a rapid-response vaccine platform. CEPI has committed up to $8.3 million in additional funding for accelerated development, manufacturing, and clinical tests. CEPI CEO Richard Hatchett said the Coalition and CureVac aspire to bring the pathogen’s gene sequence to a vaccine candidate for clinical testing “within a few months.”
Treatment: Leronlimab (PRO 140)
Type: Humanized IgG4 monoclonal antibody. Leronlimab is CytoDyn’s lead candidate, and is a CCR5 antagonist with potential for multiple therapeutic indications.
Status: CytoDyn plans to offer an update during a March 5 conference call with analysts about its planned filing of an IND and its Phase II clinical trial protocol with the FDA, as the company seeks to evaluate the leronlimab as a coronavirus treatment. CytoDyn and Longen China Group said February 12 they will begin exploring leronlimab as a potential treatment for coronavirus as well as cancer.
Leronlimab has successfully completed nine clinical trials in over 800 people, according to CytoDyn, including meeting its primary endpoints in a pivotal Phase III trial in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients. CytoDyn has said it plans to file a BLA with the FDA in HIV during Q1 2020. Leronlimab has the FDA’s Fast Track designation as a combination therapy with highly active antiretroviral therapy (HAART) for HIV-infected patients, and for metastatic triple-negative breast cancer.
Fujifilm Holdings and Zhejiang Hisun Pharmaceutical
Treatment: Favipiravir (marketed by Fujifilm as Avigan and by Hisun in China as Favilavir)
Type: Broad spectrum anti-viral agent that is designed to selectively and potently inhibit the RNA-dependent RNA polymerase (RdRp) of RNA viruses. Japan has approved Avigan for novel or re-emergent influenza and was previously used to treat Ebola patients in Guinea.
Status: Japan’s Health Minister Katsunobu Kato said February 22 that his ministry would recommend Avigan, developed by Fujifilm-owned Toyama Chemical, for use as a coronavirus treatment after test dosages appeared effective in mild and asymptomatic cases at least two medical institutions. In China, the National Health Commission on February 17 approved Hisun’s version of the drug as an investigational treatment for SARS-CoV-2 in an upcoming clinical trial being conducted in Shenzhen.
Treatment: Ii-Key peptide vaccine
Type: Vaccine based on Generex’s Ii-Key immune system activation technology platform
Status: Generex said February 27 it has received a contract from the China Technology Exchange, Beijing Zhonghua Investment Fund Management Co. Ltd., Biology Institute of Shandong Academy of Sciences, and Sinotek-Advocates International Industry Development (Shenzhen) Co. Ltd. to develop a Ii-key vaccine. Generex said it would receive $1 million upfront to initiate project work in the U.S., a $5 million licensing fee for the Ii-Key technology, payment by the Chinese consortium for all costs and expenses related to the development of a COVID-19 vaccine, and a 20% royalty on each dose of vaccine produced.
Treatment: Remdesivir (GS-5734)
Type: Nucleotide prodrug
Status: The NIH announced February 25 it will run the first U.S. clinical trial evaluating an experimental treatment for COVID-19, by assessing remdesivir in patients at the University of Nebraska Medical Center in Omaha, where some Americans with the disease are being cared for or are under quarantine. Remdesivir showed “no adverse events” when administered to the first American confirmed to be infected with SARS-CoV-2, members of the Washington State 2019-nCoV Case Investigation Team reported in a case study published January 31 in The New England Journal of Medicine.
In China, clinical trials of Gilead Sciences’ remdesivir have begun after China’s National Medical Products Administration approved applications by the China-Japan Friendship Hospital and the Chinese Academy of Medical Sciences to conduct the studies. Remdesivir and chloroquine phosphate were “highly effective in the control of 2019-nCoV infection in vitro,” a team of Chinese researchers reported in a study published February 4 in Cell Research.
GlaxoSmithKline and Clover Biopharmaceuticals
Treatment: COVID-19 S-Trimer
Type: Protein-based coronavirus vaccine
Status: GSK agreed to provide Clover with its pandemic adjuvant system for further evaluation of S-Trimer in preclinical studies, the companies said February 24, under a research collaboration whose value was not disclosed. GSK reasons that Clover could rapidly scale-up and produce large-quantities of a new coronavirus vaccine since it has one of the largest in-house, commercial-scale cGMP biomanufacturing capabilities in China.
“GSK is the world leader in vaccines, and partnering with them significantly boosts our hopes of both the timely development of a vaccine, and the capability to produce it in large enough quantities necessary to curb the coronavirus outbreak,” said Michael Breen, director, Infectious Diseases, Pharma at GlobalData.
iBio and Beijing CC-Pharming
Type: Plant-derived vaccine to be manufactured using iBio’s FastPharming SystemTM
Status: The companies on February 3 disclosed plans to develop and test a COVID-19 vaccine, combining the vaccine R&D experience—including work on the MERS-coronavirus—by CC-Pharming Chairman and chief scientific officer Kevin Wang, PhD, and iBio VP Upstream Bioprocessing Sylvain Marcel, PhD, in rapid design of manufacturing processes for biopharmaceutical production in plant-based expression systems. If successful, the research will deliver product candidates for production at
iBio’s FastPharming Manufacturing Facility, built in 2010 with funding from the Defense Advanced Research Projects Agency (DARPA), to establish facilities capable of rapid delivery of medical countermeasures in response to a disease pandemic.
Treatments: Vaccines and coronavirus-neutralizing antibodies
Types: Prophylactic and therapeutic compounds using ImmunoPrecise’s proprietary discovery platforms (including B Cell Select™ and DeepDisplay™) and ImmunoPrecise subsidiary Talem Therapeutics’ access to the transgenic animal platform OmniAb® for direct generation of human antibodies.
Status: ImmunoPrecise announced its commitment to finding COVID-19 treatments on February 20, saying it had designated Ilse Roodink, PhD, chairwoman of Talem’s scientific committee, as its Coronavirus Global Project Leader.
Incyte, Shanghai Hengrui Pharmaceutical
Treatment: Camrelizumab and thymosin
Types: Humanized monoclonal antibody targeting PD-1 (Camrelizumab); 5-Da polypeptide hormone secreted by the thymus gland (thymosin)
Status: Chinese clinical trials assessing the combination treatment have been registered by Wuhan Jinyintan Hospital (Wuhan Infectious Diseases Hospital) (ChiCTR2000029806) and Southeast University (NCT04268537).
Type: Defensin mimetic in Phase II development in oral muscositis in Head and Neck Cancer patients
Status: Innovation said February 24 that it submitted a Material Transfer Agreement with an unidentified “leading U.S.-based virology laboratory” to study Brilacidin as a potential novel treatment for SARS-CoV-2. If lab tests prove successful, Innovation said, it will expedite research and clinical development of Brilacidin “via pharmaceutical partnerships, academic collaborations and government grants.” Innovation has also submitted a preliminary summary of Brilacidin’s potential for treating coronavirus to the Biomedical Advanced Research and Development Authority (BARDA).
Inovio Pharmaceuticals and Beijing Advaccine Biotechnology
Status: Inovio said January 30 it will leverage Beijing Advaccine Biotechnology’s expertise to run a Phase I trial in China in parallel with the company’s clinical development efforts in the U.S. to develop INO-4800 as a coronavirus treatment. The company has said it will develop INO-4800 through Phase I testing in the U.S., and has launched preclinical testing for clinical product manufacturing. Development of INO-4800 is supported by $9 million grant from the Coalition for Epidemic Preparedness Innovations (CEPI).
Janssen Pharmaceutical Cos. (Johnson & Johnson)
Treatments: Prezcobix™ (darunavir and cobicistat); Vaccine to be developed with BARDA
Types: HIV protease inhibitors (Prezcobix); vaccine type to be developed
Status: Janssen said January 29 it has donated 300 boxes of Prezcobix to the Shanghai Public Health Clinical Center and Zhongnan Hospital of Wuhan University for use in research to support efforts in finding a solution against SARS-CoV-2. Another 50 boxes have been provided to the Chinese Center for Disease Control and Prevention for laboratory-based investigations. Prezcobix is under study in a trial sponsored by Shanghai Public Health Clinical Center (NCT04252274), while a Chinese trial is assessing Precobix or the lopinavir-ritonavir combination combined with thymosin a1 (ChiCTR2000029541).
Separately, Janssen said February 11 it has expanded an existing collaboration with the Biomedical Advanced Research and Development Authority (BARDA) to develop a vaccine candidate for SARS-CoV-2. The partners agreed to share R&D costs and expertise to help accelerate Janssen’s investigational COVID-19 vaccine into clinical trials. Janssen said it is also working closely with global partners to screen its library of antiviral molecules to accelerate discovery of potential COVID-19 treatments.
LineaRx (Applied DNA Sciences) and Takis Biotech
Treatment: Linear DNA vaccine
Type: To be based on PCR-produced linear DNA designed to induce antibodies that can neutralize SARS-CoV-2
Status: LineaRx, a majority-owned subsidiary of Applied DNA Sciences of Stony Brook, NY, and Rome-based Takis Biotech said February 7 they have formed a joint venture to develop the preclinical vaccine using PCR-based DNA manufacturing technology. No commercial partner to take the coronavirus vaccine to market has been identified, the companies said.
The companies said advantages of their technology include the speed of production, the absence of antibiotics and their resistance genes, the purity of the DNA, the simplicity of design, the powerful immunogenicity proved in a prior linear DNA vaccine, the absence of any bacterial contaminants and the effectiveness of the vaccine gene without insertion into the patient’s genome.
Type: Novel lipid nanoparticle (LNP)-encapsulated mRNA vaccine against the COVID-19 encoding for a prefusion stabilized form of the Spike (S) protein.
Status: Moderna said February 24 that it shipped the first batch of mRNA-1273 to the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) for use in a planned Phase I study in the U.S. The primary aim of the Phase I open-label, dose-ranging trial study (NCT04283461), which had yet to recruit patients at deadline, is to evaluate the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 3 dosages in healthy adults. Moderna designed the vaccine in collaboration with investigators at the NIAID Vaccine Research Center (VRC).
Treatment: Antiviral therapy based on company’s novel nanomedicines platform.
Type: Broad-spectrum virus-binding ligand: “It is like a ‘Venus-Fly-Trap’ for the virus,” says Anil R. Diwan, PhD, President and Executive Chairman.
Status: NanoViricides confirmed January 30 that it was developing a COVID-19 treatment, stating that it “already found some lead candidate ligands in its chemical library” that can bind to the SARS-CoV spike protein just as it binds to cognate receptor ACE2.
NanoViricides’ technology relies on copying the human cell-surface receptor to which the virus binds, and making ligands that chemically attach to a nanomicelle, to create a nanoviricide®. When a virus comes in contact with the nanoviricide, the nanomicelle polymer is designed to fuse with the virus lipid envelope.
The company said it has started preparing for testing of potential candidates in cell cultures against “low-threat” coronaviruses, including ones that use the ACE2 receptor, in its own BSL-2 virology laboratory at its Shelton, CT, campus. NanoViricides added that it is working on developing collaborations to advance its COVID-19 program should an effective drug candidate be identified.
Treatment: Vaccine candidate to be selected
Types: Vaccines designed to apply company’s proprietary recombinant protein nanoparticle technology platform to generate antigens derived from the coronavirus spike (S) protein. Novavax said it expects to utilize its proprietary saponin-based Matrix-M™ adjuvant with COVID-19 vaccine candidates to enhance immune responses.
Status: “We are now well-positioned to advance the COVID-19 vaccine candidate to Phase I clinical testing in May or June,” President and CEO Stanley C. Erck said February 26 in a statement. Novavax cited progress in its development saying it has produced and is currently assessing multiple nanoparticle vaccine candidates in animal models prior to identifying an optimal candidate for human testing.
Treatment: Arbidol (umifenovir)
Type: Membrane fusion inhibitor developed as a treatment for influenza
Status: Pharmstandard is assessing Arbidol in clinical trials as monotherapy and in combinations that include AbbVie’s Kaletra (See above), Ascletis Pharma’s ASC09 (See above), lopinavir, ritonavir, carrimycin, and Bromhexine Hydrochloride (enrolling by invitation). Five trials including Arbidol were listed on ClinicalTrials.gov. China’s Ruijin Hospital is conducting the monotherapy trial (NCT04260594), while various Chinese hospitals are investigating the combination therapies (NCT04252885, NCT04273763, NCT04261907, NCT04286503).
Q Biomed and Mannin Research
Treatment: Drug to treat vascular diseases in people with COVID-19
Type: Adjunct treatment for vascular leakage and endothelial dysfunction seen in COVID-19 and other infectious diseases, to be developed based on the lead platform of research partner Mannin Research, which is designed to target the activation of the Angiopoietin-Tie2 signaling pathway.
Status: Q Biomed and Mannin Research announced their collaboration on February 4. In September 2019, the German state of Saxony awarded Mannin approximately a US $7.7 million grant to advance its novel therapeutics, including drugs and biologics that reduce endothelial dysfunction and loss of endothelial barrier integrity. Mannin recently submitted a funding application to the NIH’s Small Business Technology Transfer Grant to investigate specific applications of Mannin’s therapeutic platform.
Treatments: REGN3048 and REGN 3051
Types: Combination of neutralizing monoclonal antibodies leveraging Regeneron’s monoclonal antibody discovery platform called VelocImmune®, part of the company’s VelociSuite™ technologies.
Status: On February 4, The Biomedical Advanced Research and Development Authority (BARDA) said it was expanding upon an earlier partnership agreement with Regeneron to develop “multiple monoclonal antibodies that, individually or in combination, could be used to treat new treatments.” The combination completed a Phase I trial in MERS-CoV last year (NCT03301090).
Treatment: Unnamed vaccine
Type: Vaccine based on Sanofi’s recombinant DNA platform, designed to produce an exact genetic match to proteins found on the surface of the virus. Sanofi said the DNA sequence encoding the antigen will be combined into the DNA of the baculovirus expression platform and used for rapidly producing large quantities of the coronavirus antigen, which will be formulated to stimulate the immune system to protect against the virus.
Status: Sanofi said February 18 that its Sanofi Pasteur vaccines global business unit will apply previous development work for a SARS vaccine with the aim of accelerating development of a COVID-19 vaccine through a collaboration with the Biomedical Advanced Research and Development Authority (BARDA). In non-clinical studies, the SARS vaccine candidate was immunogenic and afforded partial protection as assessed in animal challenge models, Sanofi said. That earlier work by Protein Sciences, acquired by Sanofi in 2017, “provides a head start in expediting a COVID-19 vaccine,” Sanofi stated.
Tonix Pharmaceuticals Holding
Type: Live modified horsepox virus vaccine for percutaneous administration
Status: Tonix said February 26 it has partnered with Southern Research to develop TNX-1800 as a vaccine treatment for COVID-19. TNX-1800 is under development as a potential smallpox preventing vaccine for the U.S. strategic national stockpile and as a monkeypox preventing vaccine.
Treatment: Vaccine based on proprietary VAASTM Platform
Type: Oral recombinant vaccine administered by tablet
Status: Vaxart said January 31 that it plans to generate vaccine candidates based on the published genome of the 2019 COVID-19 (SARS-nCoV-2) and evaluate them in preclinical models based on their ability to generate both mucosal and systemic immune responses.
Vir Biotechnology and WuXi Biologics
Treatment: As-yet undisclosed human monoclonal antibodies
Type: Human monoclonal antibodies shown to bind to SARS-CoV-2, isolated from individuals who had survived a Severe Acute Respiratory Syndrome (SARS) infection.
Status: Vir Biotechnology on February 25 announced a development and manufacturing collaboration With WuXi Biologics to advance and produce human monoclonal antibodies as potential treatments for COVID-19. The antibodies were discovered through the company’s antibody platform, which has been used to identify and develop antibodies for pathogens that include Ebola (mAb114, currently in use in the Democratic Republic of Congo), hepatitis B virus, influenza A, malaria, and others. Should the antibodies receive regulatory approvals, WuXi Biologics has rights to commercialize therapies in Greater China and Vir, in all other markets worldwide.
COVID-19 related protocols, data and products