Pharma COVID Roundup: News from AstraZeneca, Pfizer, Gilead, Merck & Co.

The latest on manufacturing and potential treatments for COVID-19 with news from AstraZeneca, Pfizer, Gilead Sciences, Daiichi Sankyo, Merck & Co., Merck KGaA, and others.

News from AstraZeneca, Daiichi Sankyo, Merck KGaA, Gilead, and Merck & Co.

AstraZeneca, Brazil Form $127-M Supply Contract for COVID-19 Vaccine
The Brazilian government has signed a $127-million agreement with the UK government and AstraZeneca for supply and technology transfer of an investigational COVID-19 vaccine being developed by AstraZeneca and the University of Oxford.

The agreement is divided into two phases. In the first phase, Brazil’s Ministry of Health is purchasing 30 million doses initially at risk (meaning prior to the demonstration of the vaccine’s effectiveness). The second phase involves the purchase of 70 million doses, dependent on the vaccine’s efficacy and safety.

It is projected that the first doses will be available in December of this year (December 2020) and January 2021, according to Brazil’s Ministry of Health.

Source: Government of Brazil (in Portuguese)

Daiichi Sankyo, AstraZeneca In Talks for Supply of COVID-19 Vaccine
Daiichi Sankyo is in discussions with AstraZeneca to supply Japan with a COVID-19 vaccine candidate, AZD1222, being developed by AstraZeneca and Oxford University.

AstraZeneca has agreed to advance specific discussions with the Japanese government toward the introduction of the vaccine in Japan, and based on that agreement, Daiichi Sankyo has decided to advance discussions with AstraZeneca to formulate the vaccine, including vial filling, packaging, and storage in Japan.

The plan, once agreed to, involves Daiichi Sankyo Biotech, a subsidiary of Daiichi Sankyo, to receive the undiluted solution from AstraZeneca and then carry out formulation procedures.

Separately, Daiichi says it plans to continue working on its R&D program on a nafamostat inhalation formulation for the treatment of COVID-19 as well as a separate mRNA vaccine candidate.

Source: Daiichi Sankyo

Pfizer, BioNTech Report Preliminary Data for COVID-19 Vaccine Candidate
Pfizer and BioNTech, a Mainz, Germany-based immunotherapy company, reported this week (July 1, 2020) preliminary data from their BNT162 mRNA-based vaccine program against SARS-CoV-2, the virus causes COVID-19. Earlier this year (April 2020), Pfizer and BioNTech formed a collaboration, worth up to $748 million ($185 million upfront), to develop vaccine candidates against COVID-19.

The BNT162 program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target antigen. Overall, the preliminary data demonstrated that one of the vaccine candidates, BNT162b1, could be administered in a dose that was well tolerated and generated dose-dependent immunogenicity. The ongoing US Phase I/II randomized, placebo-controlled, observer-blinded study was initiated in May 2020 and is evaluating the immunogenicity of escalating dose levels of BNT162b1.

The companies say the preliminary data, together with additional preclinical and clinical data being generated, will be used by the two companies to determine a dose level and select among multiple vaccine candidates to seek to progress to a large, global Phase IIb/III trial. That trial may involve up to 30,000 healthy participants and is anticipated to begin in late July 2020, if regulatory approval to proceed is received.

The BNT162b1 candidate remains under clinical study and is not currently approved for distribution anywhere in the world. If the ongoing studies are successful and the vaccine candidate receives regulatory approval, the companies expect to manufacture up to 100 million doses by the end of 2020 and potentially more than 1.2 billion doses by the end of 2021. In that event, BioNTech and Pfizer would work jointly to distribute the potential COVID-19 vaccine worldwide (excluding China, where BioNTech has a collaboration with Fosun Pharma for BNT162 for both clinical development and commercialization). The development of the vaccine is also supported by partners, such as Acuitas Therapeutics, a Canadian company that provides lipid nanoparticles for the formulation of various mRNA vaccines.

In a separate development, BioNTech, announced a private investment of $250 million, which includes an investment of approximately $139 million in ordinary shares and a $112-million investment in four-year mandatory convertible notes. The investment is expected to close in early- to mid-August (August 2020), subject to customary closing conditions.

Source: Pfizer and BioNTech (Vaccine trials) and BioNTech (private placement)

Merck KGaA Initiates Clinical Trial of Potential COVID-19 Treatment
Merck KGaA reports that the US Food and Drug Administration (FDA) has cleared its investigational new drug application for M5049, a potential treatment of COVID-19 pneumonia.

M5049 is a small molecule that blocks the activation of toll-like receptors (TLR), TLR7 and TLR8, two innate immune sensors that detect single-stranded RNA from viruses, such as SARS-CoV-2, the virus that causes COVID-19, according to information from the company. Activation of TLR7/8 leads to immune-cell activation and inflammation, which when not properly controlled can cause severe immunopathology. The company says it will initiate a Phase II randomized, controlled clinical study evaluating the safety and efficacy of M5049 and evaluate if M5049 intervention may prevent or ameliorate the hyper-inflammatory response in patients with COVID-19 pneumonia and prevent progression of the “cytokine storm” associated with COVID-19.

Merck KGaA says it expects results from the Phase II study around the end of 2020.

Source: Merck KGaA

Gilead Sets Price on COVID-19 Antiviral Drug Remdesivir
Gilead Sciences has set a list price for governments of developed countries of $390 per vial of remdesivir, an investigational antiviral drug being evaluated for treating COIVD-19. Daniel O’Day, Gilead’s CEO and Chairman, made the announcement in a June 29, 2020 statement.

Based on current treatment patterns, the majority of patients are expected to receive a five-day treatment course using six vials of remdesivir, which equates to a cost of treatment of $2,340 per patient. In the US, O’Day says the same government price of $390 per vial will apply, but that because of the way the US system is set up and the discounts that government healthcare programs expect, the price for US private insurance companies will be $520 per vial.

Gilead has entered into an agreement with the US Department of Health and Human Services (HHS), whereby the HHS and US states will continue to manage allocation to hospitals until the end of September (September 2020). After this period, once supplies are less constrained, the HHS will no longer manage allocation.

For the developing world, where healthcare resources, infrastructure, and economics are different, Gilead has entered into agreements with generic manufacturers to deliver treatment at lower costs.

O’Day says by the end of this year (2020), Gilead expects its investment on the development and manufacture of remdesivir to exceed $1 billion, and the company’s commitment will continue through 2021 and beyond.

Source: Gilead Sciences

HHS Secures 500,000 Courses of Remdesivir for Hospital Distribution
The US Department of Health and Human Services has announced an agreement to secure large supplies of Gilead Sciences’ remdesivir, an investigational antiviral drug being evaluated for treating COIVD-19, for the US through September (September 2020).

This agreement will allow hospitals to purchase remdesivir in amounts allocated by the HHS and state health departments. The HHS has secured more than 500,000 treatment courses. This represents 100% of Gilead’s projected production for July 2020 (94,200 treatment courses), 90% of production in August 2020 (174,900 treatment courses), and 90% of production in September 2020 (232,800 treatment courses), in addition to an allocation for clinical trials. A treatment course of remdesivir is, on average, 6.25 vials.

Hospitals will receive the product shipped by AmerisourceBergen, a US drug wholesaler,  and will pay no more than Gilead’s wholesale acquisition price, which amounts to approximately $3,200 per treatment course.

The HHS says generally, patients do not pay directly for hospital-administered drugs such as remdesivir; rather, for Medicare and most private insurers, the drug’s cost is incorporated into payments made by the insurer, such as Medicare paying for the drug through a diagnostic-related group.

These supplies will be allocated in the same way that Gilead’s donation of approximately 120,000 treatment courses of remdesivir was allocated. The HHS will allocate product to state and territorial health departments based on COVID-19 hospital burden, and health departments will allocate it to hospitals. The delivery of the purchased remdesivir will be streamlined, going directly to the hospital, per the state’s allocation decision, rather than going first to the state health departments for subsequent delivery to hospitals.

The HHS says shipments will likely occur every two weeks as they have with the donated product. The final allocation of Gilead’s approximately 120,000 donated treatment was shipped on June 29, 2020).

Source: The US Department of Health and Human Services

Hetero Labs Gets OK in India for Gilead’s Remdesivir for COVID-19
Hetero Labs, a Hyderabad, India-headquartered active pharmaceutical ingredient producer and part of its pharmaceutical parent company Hetero Drugs, has received manufacturing and marketing approval for Gilead Sciences’ investigational antiviral medicine, remdesivir, from the Drug Controller General of India for the treatment of COVID-19. Hetero’s generic version of remdesivir will be marketed under the brand name Covifor in India.

Following the approval of Covifor, a group company of Hetero is set to deliver the first set of 20,000 vials in two equal lots of 10,000 each.

One lot will be immediately supplied to Hyderabad, Delhi, Gujarat, Tamil Nadu, Mumbai, and other parts of Maharashtra while the other lot will be supplied to Kolkata, Indore, Bhopal, Lucknow, Patna, Bhubaneshwar, Ranchi, Vijayawada, Cochin, Trivandrum, and Goa within the week (as reported on June 24, 2020) in order to meet emergency requirements. The company says the product is priced at Rs. 5,400 ($71) per vial.

In May 2020, Gilead signed non-exclusive voluntary licensing agreements with five generic pharmaceutical manufacturers, including Hetero Labs, to further expand supply of remdesivir as a potential treatment for COVID-19.

Source: Hetero Labs (launch) and Hetero Labs (20,000 vials)

EMA Committee Gives Conditional OK for Gilead’s COVID-19 Drug
The Committee for Medicinal Products for Human Use of the European Medicines has recommended granting a conditional marketing authorization for remdesivir, Gilead Sciences’ investigational antiviral for the treatment of COVID-19 in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen.

A conditional marketing authorization is one of the regulatory mechanisms of the European Union to facilitate early access to medicines that fulfill an unmet medical need. It allows the EMA to recommend a medicine for marketing authorization with less complete data than normally expected, if the benefit of a medicine’s immediate availability to patients outweighs the risk inherent to the fact that not all the data are yet available.

In order to better characterize the effectiveness and safety of remdesivir, the EMA says Gilead will have to submit final reports of remdesivir studies to the EMA by December 2020, and further data on the quality of the medicine, as well as the final data on mortality, by August 2020.

The European Commission, which was kept informed by the EMA throughout the evaluation process, will fast-track the decision-making process and aims to grant a decision on the conditional marketing authorization for remdesivir in the coming week (as reported on June 25, 2020) to allow the product to be marketed in the EU.

Source: European Medicines Agency

Merck & Co., Ridgeback Close Deal for COVID-19 Antiviral Candidate
Merck & Co. and Ridgeback Biotherapeutics, a Miami, Florida-based biopharmaceutical company focused on orphan and emerging infectious diseases, have completed the requirements for their previously announced partnership transaction to advance the development of EIDD-2801, an investigational orall antiviral agent currently in early clinical development for treating COVID-19.

The US Federal Trade Commission (FTC) granted early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

Merck & Co., through a subsidiary, has acquired exclusive rights to develop EIDD-2801 and related molecules in collaboration with Ridgeback. Ridgeback will continue to fund and conduct multiple Ridgeback-sponsored Phase I and II trials and fund manufacturing campaigns for clinical supply. Going forward, the parties will collaborate on clinical development for COVID-19 and manufacturing, to be led by Merck. Merck and Ridgeback say they also plan to explore the potential for EIDD-2801 in other severe acute viral diseases, such as Ebola.

Source: Merck & Co.

News from Dr. Reddy’s, Glenmark, Oxford University, Novavax, Inovio

Dr. Reddy’s, Fujifilm, GRA Partner for Potential COVID-19 Antiviral
Dr. Reddy’s Laboratories, a Hyderabad, India-headquartered pharmaceutical company, has partnered with Fujifilm and Global Response Aid (GRA), a Dubai-based company that offers medical supplies, drugs, and medical services in cooperation with drug and medical device manufacturers, for the development, manufacture, and sale of Fujifilm’s Avigan (favipiravir), an antiviral drug for influenza that is being evaluated for treating patients with COVID-19.

Under the agreement, Fujifilm grants Dr. Reddy’s the exclusive rights of manufacturing and also grants both Dr. Reddy’s and GRA the rights to develop, sell, and distribute Avigan in all countries other than Japan, China, and Russia. Dr. Reddy’s will have exclusive rights for the development, selling, and distribution of Avigan in India. Fujifilm will also receive an upfront license fee and royalties on sales from Dr. Reddy’s and GRA.

Fujifilm will provide Dr. Reddy’s and GRA with data on Avigan’s preclinical and clinical studies that Fujifilm has accumulated thus far. Dr. Reddy’s and GRA will use this data for clinical studies targeting COVID-19 in regions where infection has been spreading. In addition, Fujifilm will grant Dr. Reddy’s the right to use Avigan’s patents of formulation and manufacturing methods. Dr. Reddy’s will establish a set-up for manufacturing drugs of the same quality as Avigan, and use GRA’s global sales network to supply the manufactured drugs.

Fujifilm is currently conducting a clinical study on Avigan targeting COVID-19 patients in Japan and the US and is working to increase the drug’s production by partnering with domestic and overseas companies. Dr. Reddy’s and GRA will introduce the product in the market post all applicable approvals in the respective countries.

Source: Dr. Reddy’s Laboratories and Fujifilm

Glenmark Receives Approval to Launch Oral Antiviral to Treat COVID-19
Glenmark Pharmaceuticals, a Mumbai, India-headquartered pharmaceutical company, has received manufacturing and marketing approval from India’s drug regulator to launch the antiviral drug, favipiravir, a generic form of Fujifilm Toyama Chemical’s Avigan, an antiviral drug being evaluated to treat COVID-19.

Glenmark will launch favipiravir under the brand name FabiFlu. Glenmark says it developed the active pharmaceutical ingredient and the formulation for FabiFlu through its R&D team. Glenmark filed the product for clinical trials with India’s drug regulator, the Drug Controller General of India, and received approval for conducting Phase III clinical trial in mild-to-moderate COVID-19 patients.

Source: Glenmark Pharmaceuticals

Dexamethasone Reports Promising Results as Potential COVID-19 Treatment
Researchers at the University of Oxford reported last month (June 16, 2020) promising results for dexamethasone, a steroid drug, as a potential COVID-19 treatment based on results from its Recovery clinical trial.

A total of 2,104 patients were randomized to receive dexamethasone 6 mg once per day for 10 days and were compared with 4,321 patients randomized to usual care alone. Among the patients who received usual care alone, a 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).

The data further showed that dexamethasone reduced deaths by one-third in ventilated patients and by one fifth in other patients receiving oxygen only. There was no benefit among those patients who did not require respiratory support.

Source: The University of Oxford

Novavax Appoints CMC Head for COVID Vaccine Candidate
Novavax, a Gaithersburg, Maryland-based clinical-stage vaccine company, has announced the appointment of Ben Machielse as Executive Vice President of Chemistry, Manufacturing and Controls (CMC), with responsibility for overseeing Novavax’ manufacturing, process technology, quality and regulatory functions.

Novavax says the addition of Mr. Machielse supports its commitment to progressing its pipeline programs to produce a global supply of NVX-CoV2373, the company’s COVID-19 vaccine candidate, and in growing its influenza production capabilities.

Mr. Machielse has more than 25 years of biotechnology industry experience and was most recently Chief Executive Officer of the rare disease company, Vtesse, before its acquisition by Sucampo Pharmaceuticals, now a part of Mallinckrodt. Previously, he was Chief Operating Officer at Omthera Pharmaceuticals, where he oversaw development and approval of a treatment for hypertriglyceridemia and was integral to the company’s initial public offering and acquisition by AstraZeneca. Earlier, as Executive Vice President of Operations for MedImmune, later acquired by AstraZeneca, he led worldwide development and operations of the company’s therapeutic antibody, small-molecule and vaccine products.

Source: Novavax

Inovio’s COVID-19 Vaccine Selected for US’ Operation Warp Speed
Inovio, a Plymouth Meeting, Pennsylvania-based biopharmaceutical company developing DNA-based immunotherapies for cancer and infectious diseases, has announced that INO-4800, its vaccine candidate against SARS-CoV-2, the virus that causes COVID-19, has been selected to participate in a non-human primate (NHP) challenge study as part of the US government program, Operation Warp Speed, which seeks to provide quantities of COVID-19 vaccines in the US by January 2021. Its selection follows positive interim clinical data of INO-4800 from two Phase I clinical trial cohorts.

The Phase I clinical trial of INO-4800 initially enrolled 40 healthy adult volunteers 18 to 50 years of age at two US sites with funding from the Coalition for Epidemic Preparedness Innovations (CEPI), a public–private partnership for vaccine development. The participants were enrolled into 1.0 mg and 2.0 mg dose cohorts; each participant received two doses of INO-4800 four weeks apart. There were no reported serious adverse events. Furthermore, Inovio has expanded its Phase I trial to add older participants in additional cohorts and plans to initiate a Phase II/III efficacy trial this summer (summer 2020) upon regulatory concurrence.

INO-4800 is currently being tested in a ferret challenge model and in NHP challenge studies as part of Operation Warp Speed.

As previously announced, INOVIO received $71 million funding from the US Department of Defense to support the large-scale manufacture of the company’s proprietary vaccine-delivery devices (Cellectra 3PSP smart device) and the procurement of Cellectra 2000 devices, which are used to deliver INO-4800. INO-4800 development has also been supported by funding from CEPI and the Bill & Melinda Gates Foundation.

Source: Inovio

NeuroRx, Relief Therapeutics Granted Fast Track for COVID-19 Treatment
NeuroRx, a clinical-stage pharmaceutical company, in partnership with Relief Therapeutics, a drug-development company, has been granted fast-track designation by the US Food and Drug Administration (FDA) for RLF-100 (aviptadil) for treating acute lung injury/acute respiratory distress syndrome associated with COVID-19.

RLF-100 is a synthetic form of human vasoactive intestinal peptide (VIP), which reduces inflammation in the lungs and protects the alveolar Type II cells that are believed to be an entry route for the SARS-CoV-2, the virus that causes COVID-19.

As part of NeuroRx’s enrollment in the fast-track program, the FDA has requested that NeuroRx submit a publicly available expanded access policy, so that physicians may request RLF-100 for their patients who are being treated in hospitals not participating in the ongoing Phase II/III clinical trials.

RLF-100 is being tested in Phase II/III clinical trials at several medical centers, including the University of Miami, Houston Methodist Hospital, the University of California-Irvine, New York University’s Langone Medical Center, and the Rambam Healthcare Campus in Haifa, Israel.

Source: Relief Therapeutics

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