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Pharma Takes on COVID-19

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Lonza and Humanigen, a clinical-stage biopharmaceutical company focused on the treatment of immune hyper-response (cytokine storm), announced on Sept. 15, 2020 that they have entered into a strategic collaboration to expand the manufacturing capacity for lenzilumab, a therapeutic candidate for COVID-19 currently in Phase III clinical trials. The partnership for manufacturing expansion is established in advance of a potential Emergency Use Authorization expected in 2020 and subsequent commercialization.

Lenzilumab comes from Humanigen's proprietary Humaneered anti-human granulocyte macrophage-colony stimulating factor (GM-CSF) monoclonal antibody (mAb) platform. This mAb has the potential to prevent and treat cytokine storm, which is believed to trigger the acute respiratory distress syndrome in severe cases of COVID-19.

The collaboration between Lonza and Humanigen enables Humanigen to leverage Lonza's mAb manufacturing and regulatory expertise and provides Humanigen with additional capacity for current good manufacturing practices (CGMP) production of lenzilumab. Operations are intended to start in 2021 and production of lenzilumab will begin at Lonza's 2000-L manufacturing facilities in Hayward, CA. Technology transfer is expected to begin in the third quarter of 2020.

"In an effort to change the course of this pandemic, advancing lead COVID-19 therapeutics requires matched supply chain efforts and expertise to meet the continued and urgent patient needs. COVID-19 has highlighted the need for heightened industry collaboration and coordination and we are excited to work closely with Humanigen as we work to combat this global health crisis," said Jean-Christophe Hyvert, chief commercial officer, Lonza, in a company press release.

"We are ramping up our manufacturing efforts for lenzilumab, our lead drug candidate, and this collaboration with Lonza, a global manufacturing leader with expertise in technology transfer and an established track record of working with regulatory bodies for approved and commercialized products, comes at a crucial time to meet production demand for COVID-19 therapeutics this winter," stated Cameron Durrant, MD, CEO, Humanigen, in the press release.

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The collaboration will expand the manufacturing capacity for lenzilumab, a COVID-19 therapeutic candidate, in advance of a potential Emergency Use Authorization in 2020.

Lonza, Humanigen Partner to Expand Manufacturing of Lenzilumab for Potential COVID-19 Therapy

On Sept. 15, 2020 Novavax announced an amendment to its existing agreement with Serum Institute of India Private Limited (SIIPL) under which SIIPL will also manufacture the antigen component of Novavax’s COVID‑19 vaccine candidate, NVX‑CoV2373. With this amendment, Novavax will increases its manufacturing capacity for the vaccine candidate to more than two billion doses annually, when all planned capacity has been brought online by mid-2021.

The antigen component of the vaccine candidate is being manufactured at Novavax CZ in Bohumil, Czech Republic (formerly Praha Vaccines), in addition to the following partnered manufacturing sites:

FUJIFILM Diosynth Biotechnologies (FDB), in the United Kingdom and in North Carolina and Texas in the United States (US)

Novavax’s Matrix-M adjuvant, a component of NVX‑CoV2373, is now being manufactured at Novavax AB in Uppsala, Sweden, and in the following partnered manufacturing sites:

PolyPeptide Group, which will manufacture two key intermediaries used in Matrix-M in the US and Sweden

“Signing of the manufacturing agreement with Novavax for NVX-CoV2373 is another great milestone for both companies, which will further strengthen our existing relationship. SIIPL expertise to scale-up and manufacture NVX-CoV2373 will help ensure the supply of this most-needed vaccine,” said Adar Poonawalla, CEO of Serum Institute of India, in a company press release.

“Today’s agreement with Serum Institute enhances Novavax’[s] commitment to equitable global delivery of our COVID-19 vaccine. With this arrangement, we have now put in place a global supply chain that includes the recently acquired Praha Vaccines and partnerships with leading biologics manufacturers, enabling production on three continents,” said Stanley C. Erck, president and CEO of Novavax, in the press release. “We continue to work with extraordinary urgency to develop our vaccine, now in Phase [II] clinical trials, and for which we anticipate starting Phase [III] efficacy trials around the world in the coming weeks.”

The agreement will Increase global manufacturing capacity for Novavax’s vaccine candidate, NVX-CoV2373, to more than two-billion annualized doses when at full capacity in 2021.

Novavax in COVID-19 Vaccine Manufacturing Agreement with Serum Institute of India

On Sept. 17, 2020, Eli Lilly and Company and Amgen announced that they entered into a global antibody manufacturing collaboration that is expected to significantly increase the supply capacity available for Lilly's potential COVID-19 therapies.

Under the collaboration, the two companies will have the ability to quickly scale up production, which will allow them to serve many more patients around the world should one or more of Lilly's antibody therapies prove successful in clinical testing and receive regulatory approval. Lilly is currently involved in studying several potential neutralizing antibodies for the prevention and/or treatment of COVID-19, as either monotherapy or in combination.

"Based on our initial clinical studies, we believe that virus neutralizing antibodies, including LY-CoV-555, could play an important role in the fight against COVID-19," said Daniel Skovronsky, MD, PhD, Lilly's chief scientific officer and president of Lilly Research Laboratories, in a company press release. "Increasing the manufacturing capacity for our neutralizing antibodies through this collaboration with Amgen is a crucial next step, and together we hope to be able to produce many millions of doses even next year."

"We are impressed with Lilly's data, in particular the reduction in hospitalizations, and are enthusiastic about the potential for these neutralizing antibodies as a therapeutic for COVID-19," said David M. Reese, MD, executive vice-president of research and development at Amgen, in the press release.

"We are proud to partner with Lilly and leverage our deep technical expertise in antibody development and, in particular, our strong capabilities in the scale up and manufacturing of complex biologics. This is yet another example of the ways our industry is closely collaborating to combat this devastating disease and help patients around the world access new therapies," added Esteban Santos, executive vice-president of Operations at Amgen, in the press release.

The agreement between the two companies will significantly increase global supply capacity for Lilly's potential COVID-19 treatments.

Lilly and Amgen in Manufacturing Collaboration for COVID-19 Antibody Therapies

 on Sept. 15, 2020 that provides recommendations for the content and placement of geriatric information in labeling of prescription drugs. The guidance is meant to ensure consistent placement of this type of information in the correct sections and subsections in labeling so that it is clear and accessible to healthcare practitioners.

The draft guidance document replaces a withdrawn guidance, 

Content and Format for Geriatric Labeling 

(October 2001), and gives examples of geriatric use statements in labeling and examples of when FDA may permit applicants to omit or revise required information. In the document, the agency discusses labeling when a drug is approved for general use by adults, including geriatric patients; a drug is approved for geriatric-specific indications; and a drug is not approved for geriatric patient use.

The guidance document offers information on the placement and content of geriatric information in labeling of drugs and biologics.

FDA Gives Guidance on Geriatric Information in Labeling

Based on its review of data from the RECOVERY study arm, the European Medicines Agency’s (EMA) human medicines committee (CHMP) is endorsing the use of dexamethasone in patients requiring oxygen therapy, EMA 

 on Sept. 18, 2020. The corticosteroid dexamethasone, which has been authorized for use in the European Union for several decades, is used to treat inflammatory conditions.

According to EMA, “published data from the RECOVERY study show that, in patients on invasive mechanical ventilation, 29% of those treated with dexamethasone died within 28 days of starting dexamethasone treatment compared with 41% of patients receiving usual care, with a relative reduction of about 35%. In patients receiving oxygen without mechanical ventilation, the figures were 23% with dexamethasone and 26% with usual care, with a relative reduction of about 20%. No reduction in the risk of death occurred in patients who were not receiving oxygen therapy or mechanical ventilation. These results were supported by additional published data, including a meta-analysis conducted by the World Health Organization (WHO) which looked at data from seven clinical studies investigating the use of corticosteroids for the treatment of patients with COVID-19.”

The agency’s human medicines committee is endorsing the use of dexamethasone in COVID-19 patients requiring oxygen therapy.

EMA Endorses Dexamethasone for Use in COVID-19 Patients on Oxygen Therapy

 on Sept. 18, 2020 that its human medicines committee (CHMP) has recommended approval for Exparel (bupivacaine), for the treatment of post-operative pain; MenQuadfi (meningococcal group A, C, W and Y conjugate vaccine), to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W and Y; and Supemtek (Quadrivalent Influenza Vaccine). Market authorization under exceptional circumstances was recommended for the anthrax treatment, Obiltoxaximab SFL (obiltoxaximab). CHMP also gave a positive opinion to the biosimilar Nyvepria (pegfilgrastim) “for reducing the duration of neutropenia and the incidence of febrile neutropenia in patients treated with cytotoxic chemotherapy.”

Market authorization was recommended for the anticoagulant Rivaroxaban Accord (rivaroxaban). Rivaroxaban Accord is a generic drug used to treat and prevent venous thromboembolism, pulmonary embolism, and the prevention of atherothrombotic events. Marketing authorization was also recommended for Phelinun (melphalan) for treatment of “certain haematological and other cancers and as reduced intensity conditioning treatment prior to allogeneic haematopoietic stem cell transplantation in haematological diseases in adults and children. Hybrid applications rely in part on the results of pre-clinical tests and clinical trials of an already authorized reference product and in part on new data,” according to an EMA press release.

CHMP also gave 15 recommendations on extensions of therapeutic indication, includingDeltyba, Flucelvax Tetra, Fycompa, Lynparza, Opdivo, Symkevi, Tecentriq, Velphoro, Yervoy, Zavicefta, Zejula and two extensions of indication for Kalydeco. The committee recommended an extension of indication to Olumiant (baricitinib), to include thetreatment of moderate to severe atopic dermatitis in adult patients who are candidates for systemic therapy. Orfadin (nitisinone)was recommended for an extension of indication to include the treatment of alkaptonuria in adults.

During its September 2020 meeting, CHMP also confirmed its April 2020 opinion on the suspension of all ranitidine drugs in the European Union because of N-nitrosodimethylamine (NDMA) impurity.

The EMA recommendations include a meningococcal vaccine and the biosimilar Nyvepria.

EMA Recommends Seven Medicines for Approval

, dated Aug. 27, 2020, to Kalchem International after an inspection of the company’s Lindsay, OK, facility found violations of current good manufacturing practices (CGMPs). The inspection was conducted from February 10–21, 2020.

Specifically, according to FDA, the company shipped drug product before receiving the certificate of analysis with assay results from its contract laboratory and batch records were reviewed and approved after the batch was released. The agency requested in the warning letter that the company provide FDA with a list of chemical and microbial specifications used to analyze product batches, an assessment of the company’s laboratory practices and procedures, and a remediation plan to ensure the company’s quality unit (QU) properly functions.

The warning letter also stated that the company’s QU failed to adequately ensure that API met CGMP requirements. Records were not maintained and reviewed for each API that was relabeled, according to FDA. Re-packaging batch records were also not adequately reviewed before release. “For example, one lot of Lidocaine HCL was re-packaged with an incorrect lot number and shipped. Your QU reviewed the Chemical Repackaging record six days after the product had been shipped. The error was not detected until the FDA investigator found it during our inspection,” the letter stated. FDA asked the company to provide a risk assessment of the hazards of inadequate documentation and oversight of relabeled drugs.

The agency sent a warning letter to Kalchem International for CGMP violations found at the company’s Lindsay, OK, facility.

Oklahoma Facility Given FDA Warning

The Russian Direct Investment Fund (RDIF) has announced three deals with India, Brazil, and Mexico, during the first half of September 2020, for the supply of doses of Sputnik V, a potential COVID-19 vaccine that is currently undergoing early clinical trials.

On Sept. 9, 2020, RDIF released information on the first supply deal, which was struct with Landsteiner Scientific pharmaceutical company and involves the supply of 32 million doses of Sputnik V to Mexico. According to the release, deliveries are expected to commence in November 2020, subject to approval of the vaccine by Mexico’s regulators

A deal between RDIF and the State of Bahia (Brazil) was then announced on Sept. 11, 2020. Under the terms of this deal, RDIF has agreed to supply up to 50 million doses of the Russian vaccine to Brazil, starting in November 2020, if the Brazilian regulators issue an approval.

The most recent deal was announced in a press release on Sept. 16, 2020, and was struck with Dr. Reddy’s Laboratories in India. Through this deal, Dr. Reddy’s will cooperate on clinical trials and distribution of 100 million doses of Sputnik V in India, once regulatory approval in the country has been granted.

These deals follow on from the publication of Phase I/II data from open, non-randomized studies that were published in 

 (1). The studies were performed in Russian hospitals and included 76 healthy adults, with reported strong immune responses seen in all participants. However, multiple scientists have co-signed an open letter to the study authors and 

over concerns about the reliability of the data presented in the study (2). To date, the study authors have not issued a formal response to the open letter.

The Russian Direct Investment Fund has announced three deals with India, Brazil, and Mexico, for the supply of doses of Sputnik V, a potential COVID-19 vaccine.

Russia Completes Deals with India, Mexico, and Brazil for Sputnik V

Eli Lilly and Company and Amgen announced on Sept. 17, 2020 that they are entering into a global antibody manufacturing collaboration to expand Eli Lilly’s supply capacity for potential COVID-19 therapies.

Under the terms of the partnership, the companies will be able to scale up production and serve more patients if Eli Lilly’s potential COVID-19 antibody therapies are deemed effective in clinical trials and gain regulatory approval, an Eli Lilly press release said.

"Based on our initial clinical studies, we believe that virus neutralizing antibodies, including LY-CoV-555, could play an important role in the fight against COVID-19," said Daniel Skovronsky, MD, PhD, Eli Lilly's chief scientific officer and president of Lilly Research Laboratories, in the press release. "Increasing the manufacturing capacity for our neutralizing antibodies through this collaboration with Amgen is a crucial next step, and together we hope to be able to produce many millions of doses even next year."

"We are proud to partner with Lilly and leverage our deep technical expertise in antibody development and, in particular, our strong capabilities in the scale up and manufacturing of complex biologics,” added Esteban Santos, executive vice-president of operations at Amgen, in the press release. “This is yet another example of the ways our industry is closely collaborating to combat this devastating disease and help patients around the world access new therapies."

The companies aim to scale up production of Eli Lilly’s potential COVID-19 antibody therapies, pending regulatory approval.

Eli Lilly and Amgen Partner for COVID-19 Therapy Manufacturing Capacity

BioNTech, an immunotherapy company, announced on Sept. 17, 2020 that it has signed a share purchase agreement with Novartis to acquire its GMP certified manufacturing facility in Marburg, Germany, for additional COVID-19 vaccine production.

After the deals closes in the fourth quarter of 2020, the manufacturing site will produce up to 750 million doses per year, or more than 60 million doses per month, a BioNTech press release said. BioNTech plans to produce up to 250 million doses of its COVID-19 vaccine candidate, BNT162b2, in the first half of 2021.

The manufacturing facility currently employs 300 people and is equipped for the production of recombinant proteins, cell and gene therapies, and viral vectors, the press release said.

“This acquisition reflects BioNTech’s commitment to significantly expanding its manufacturing capacity in order to supply a potential vaccine worldwide upon authorization or approval,” said Dr. Sierk Poetting, chief financial officer and chief operating officer at BioNTech, in the press release. “We are working closely with Novartis to prepare for a smooth transition, and we look forward to welcoming the new members of our team and tapping into their impressive skills and expertise. From a strategic standpoint, the new site will bolster our vertically integrated business model with in-house manufacturing capabilities for mRNA manufacturing as well as vaccine formulation.”

BioNTech plans to produce up to 250 million doses of its COVID-19 vaccine candidate, BNT162b2, in the first half of 2021.