FDA sticks with approved vaccine dosing regimen; supply agreements announced

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Piramal Pharma Solutions (PPS), a US-based contract development and manufacturing organization, announced on Jan. 21, 2021 that it will provide Theratechnologies, a Canadian biopharmaceutical company, with good manufacturing practice (GMP) manufacturing of sterile fill/finish drug product to support TH1902 (docetaxel conjugate), Theratechnologies’ peptide-drug conjugate developmental product, as it enters into a first-in-humans clinical study.

Under the terms of the partnership, clinical material for the product will be produced at PPS’ manufacturing facility in Lexington, KY, to be used in a Phase I clinical trial, PPS said in a company press release. The trial will evaluate the safety, pharmacokinetics, maximum tolerated dose, and preliminary anti-tumor activity of TH1902 in participants with advanced solid tumors refractory to available anti-cancer therapies.

“Our Lexington team went the extra mile to provide solutions to ensure timely formulation development and production of the material,” said Peter DeYoung, CEO, PPS, in the press release. “It’s yet another example of how we are focused on working with our customers to reduce the burden of disease on patients.”

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Clinical material for a Theratechnologies product in development will be produced at PPS’ manufacturing facility in Lexington, KY.

Piramal Pharma Solutions to Provide Sterile Fill/Finish Support to Theratechnologies

Emergent BioSolutions and Humanigen announced on Jan. 25, 2021 that they are entering into a contract development and manufacturing (CDMO) services agreement to manufacture drug product of lenzilumab, Humanigen’s anti-human granulocyte macrophage-colony stimulating factor monoclonal antibody for the prevention and treatment of an immune hyper-response associated with COVID-19 called the “cytokine storm.”

Through the agreement, Emergent will use its CDMO services to manufacture drug product batches at its Baltimore, MD, drug product manufacturing facility to support the increased supply of the therapeutic candidate in anticipation of a potential emergency use authorization in the first quarter of 2021, Humanigen said in a company press release. The partnership will also offer access to manufacturing capacity reserved for and provided by the US government under Humanigen’s cooperative research and development agreement (CRADA) with the Department of Defense’s Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense, in collaboration with the Biomedical Advanced Research and Development Authority (BARDA).

“As we continue to advance lenzilumab for patients hospitalized with COVID-19, we are executing on plans to ensure that we have the necessary support for the next phase of our growth. Partnering with leading CDMOs like Emergent BioSolutions to help us build out our manufacturing capacity is a cornerstone to that strategy,” said Cameron Durrant, MD, CEO of Humanigen, in the press release. “The impact of BARDA’s support through our CRADA and its public-private CDMO partnership with Emergent is vital to our progress and bringing innovative solutions for patients with COVID-19.”

“Drug product manufacturing is a hallmark capability of our CDMO services, and we stand ready to harness our expertise to advance lenzilumab, Humanigen’s COVID-19 therapeutic candidate,” added Syed T. Husain, senior vice-president and CDMO business unit head at Emergent BioSolutions, in the press release. “Every second counts in the fight against COVID-19, and we are proud that Humanigen trusts us to rapidly deploy our clinical-to-commercial manufacturing operations to fulfill the urgent need for COVID-19 therapeutic options.”

Emergent will use its CDMO services to manufacture drug product batches to support the increased supply of the therapeutic candidate in anticipation of a potential emergency use authorization in the first quarter of 2021.

Emergent and Humanigen Form CDMO Compact for COVID-19 Therapeutic Candidate 

Merck, known as MSD outside the United States and Canada, announced on Jan. 25, 2021 that it is discontinuing the development of its SARS-CoV-2/COVID-19 vaccine candidates, V590 and V591, to focus on advancing its two SARS-CoV-2/COVID-19 therapeutic candidates, MK-4482 (molnupiravir) and MK-7110. MK-4482 (molnupiravir) is being developed in collaboration with Ridgeback Bio, a US-based biotechnology company. 

According to a company press release, the decision came about after it was concluded that while the vaccines were well tolerated in Phase I clinical studies, the immune responses from participants were lesser to those seen following natural infection and those reported for other COVID-19 vaccines. Currently, the company is advancing clinical programs and scaling up manufacturing for its therapeutic candidates.

“We are grateful to our collaborators who worked with us on these vaccine candidates and to the volunteers in the trials,” said Dr. Dean Y. Li, president, Merck Research Laboratories, in the press release. “We are resolute in our commitment to contribute to the global effort to relieve the burden of this pandemic on patients, health care systems, and communities.”

The company is discontinuing the development of its SARS-CoV-2/COVID-19 vaccine candidates, V590 and V591, to focus on advancing its two SARS-CoV-2/COVID-19 therapeutic candidates, MK-4482 and MK-7110. 

Merck Halts Development of its COVID-19 Vaccine Candidates

Pfizer and BioNTech announced on Jan. 22, 2021 that they have entered into an advance purchase agreement with COVAX, a global initiative focused on providing lower-middle-income countries with access to COVID-19 vaccines, for up to 40 million doses of the Pfizer-BioNTech COVID-19 vaccine, BNT162b2.

Under the terms of the agreement, the first doses of the vaccine will be delivered during the first quarter of 2021 and will be provided to COVAX at a not-for-profit, undisclosed price, Pfizer said in a company press release.

"At Pfizer, we believe that every person deserves to be seen, heard, and cared for. That's why from the very beginning of our vaccine development program, Pfizer and BioNTech have been firmly committed to working toward equitable and affordable access of COVID-19 vaccines for people around the world," said Pfizer Chairman and CEO Albert Bourla, in the press release. "We share the mission of COVAX and are proud to work together so that developing countries have the same access as the rest of the world, which will bring us another step closer to ending this global pandemic and proving that science will win for everyone, everywhere."

“SARS-CoV-2 does not differentiate between borders—a global pandemic requires comprehensive solutions and worldwide collaboration. COVAX is a truly global initiative and we are happy to support by making BNT162b2 available in many low- and lower-middle-income countries to help protect vulnerable people worldwide,” added Ugur Sahin, MD, CEO and co-founder of BioNTech, in the press release.

The companies have entered into an advance purchase agreement with COVAX to provide up to 40 million doses of the Pfizer-BioNTech COVID-19 vaccine, BNT162b2, to lower-middle-income countries.

Pfizer and BioNTech Enter into Agreement with COVAX for COVID-19 Vaccine Delivery 

Civica Rx announced on Jan. 21, 2021 that it is investing $124.5 million to build a 120,000-ft

 sterile injectable manufacturing facility in Petersburg, VA.

The site, which is set to be operational in three years, will feature disposable technology and advanced technology filling lines to produce 90 million vials and 50 million pre-filled syringes a year, Civica said in a company press release. Additionally, the facility will include steam sterilization capabilities, automated visual inspection and packaging lines, and controlled temperature warehousing of raw materials and finished medications.

“This is a dream come true for Civica and our hospital partners as we continue to work together to stabilize the supply of essential medicines for patients across the country,” said Martin VanTrieste, president and CEO of Civica, in the press release. “This Virginia plant and our future employees there will play an instrumental role in preventing the chronic drug shortages that have interrupted hospital operations and put patients at risk for over a decade.”

The site, which is set to be operational in three years, will feature disposable technology and advanced technology filling lines to produce 90 million vials and 50 million pre-filled syringes a year. 

Civica to Launch Sterile Injectable Manufacturing Facility in Virginia

Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.

One day after his inauguration, President Joe Biden unveiled a lengthy program for combatting COVID-19 by ramping up distribution and inoculation of millions of Americans over the next three months. This comprehensive pandemic response began with the President signing a packet of executive orders that expand COVID-19 testing and required mask-wearing on federal property and in public transportation and makes wider use of the Defense Production Act (DPA) to reduce shortages of supplies such as protective equipment, lab equipment, and vaccine production and delivery materials.

The broader national strategy sets seven goals, some fairly general, such as building public trust, safely reopening schools and businesses, advancing racial and ethnic equity, and restoring US global leadership, as outlined in a

 provides more details for implementing specific initiatives, many important to biopharmaceutical manufacturers.

More specifically, the Goal 2 strategy for ensuring access to safe and effective vaccines outlines ways to simplify allocation and distribution of preventives to states and localities across the country, acknowledging that rapid vaccination of millions of Americans requires access to a reliable supply of authorized vaccines. States will continue to play key roles in vaccine allocation and distribution, but the Biden plan also increased federal support for both state and national vaccination operations and for improved collection of data on vaccine distribution and inoculation. A stated change is to distribute most vaccine supplies as they are made, and not to withhold quantities for second doses.

The Biden plan also aims to fill gaps in supplies needed for manufacturing and production, such as biological materials and packaging and dispensing equipment. There’s support for expanding lipid nanoparticle formulation capacity to scale mRNA vaccine production and for the Biomedical Advanced Research and Development Authority (BARDA) to provide ongoing technical assistance and monitoring of contracted vaccine manufacturing facilities. The government will explore dose-sparing strategies that can potentially expand vaccine supply and will work with manufacturers to devise new packaging methods that can reduce minimum shipment sizes in order to reach rural and underserved communities more effectively.

An interesting wrinkle on the vaccine supply situation is whether Pfizer can count its vials as containing five or six doses. If the higher number is valid, than the company can meet its commitment of providing 200 million doses much sooner than July. FDA agreed in early January to update the vaccine’s fact sheet to confirm to clinicians that the vials contain a sixth dose. That change, however, puts pressure on pharmacies and clinics to extract that sixth dose, and that requires using special low dead volume syringes, which have been in short supply. Some vaccine clinics now find that Pfizer is shipping fewer vials, based on the expectation of more shots per vial, but are unable to access the extra vaccine.

Recent press reports indicate that Pfizer has agreed to allow the government to track vaccine shipments accompanied by the special syringes to better calculate the number of doses provided and their cost. At the same time, the Biden executive order authorizing greater use of the DPA to ensure sufficient production of supplies needed for vaccine distribution, such as packaging, glass vials, stoppers, and syringes, also sets the stage for utilizing this authority to obtain more dose-saving syringes able to extract six doses from the vials for the Pfizer-BioNTech vaccine.

One of the initial executive orders signed by Biden calls for issuing a high-level plan for developing and testing promising COVID-19 treatments. The President calls for the secretary of Health and Human Services (HHS) and the director of the National Institutes of Health (NIH) to devise a plan supporting large-scale randomized trials and other studies able to identify promising treatments that can be “easily manufactured, distributed, and administered, both domestically and internationally.” In emphasizing the need for randomized trials, the provision highlights the administration’s emphasis on relying on science in medical decisions, as opposed to the promotion of untested products by the Trump administration.

To limit contamination from the coronavirus, Goal 3 of the National Strategy, which seeks to mitigate spread through expanded masking and testing and an increased medical workforce, also supports accelerated research and clinical development of new treatments. Starting with a comprehensive preclinical drug discovery and development program of treatments that can be readily scaled and administered, it also calls for diverse clinical trials to ensure that new therapies address the needs of communities of color, children, pregnant women, and high-risk populations. And it aims to improve access to more affordable, high-quality treatments by preventing shortages through investment in advanced biopharmaceutical manufacturing, advanced purchase agreements, and strengthened surveillance systems.

The comprehensive vaccination campaign also supports ongoing vaccine R&D as a way to bolster vaccine access. Important goals are for the government to fund research and testing of vaccines for adolescents and children and the development of formulations that may be easier to deliver and administer. To assess whether current vaccines remain effective against new viral strains, NIH, FDA and BARDA will evaluate the need to alter current vaccines. FDA is cited as key to authorizing effective vaccines for rapid delivery, for assessing emerging viral mutations, and for establishing recommendations for dosing and expanding vaccine supply.

These initiatives, moreover, look to support drug discovery and development programs to combat future pandemic threats, as well as the current virus. This larger program will develop broad-spectrum antivirals to protect against the coronavirus family, which includes SARS, MERS, as well as COVID-19. There’s an emphasis on developing basic preclinical tools for vaccine testing, including assays, high throughput screening of existing and novel chemicals, 

 testing, and pharmacokinetics. And it will advance chemistry, manufacturing, and controls and regulatory efforts to support early phase clinical trials.

The broader national strategy sets seven goals, some fairly general, such as building public trust, safely reopening schools and businesses, advancing racial and ethnic equity, and restoring US global leadership.

Biden Pandemic Plan Highlights Vaccine Access and Therapeutic Development

Eli Lilly and Company announced on Jan. 22, 2021 that it has completed its $1.5 billion acquisition of Prevail Therapeutics, a US-based gene therapy company.

Through the acquisition, Lilly will have access to Prevail’s portfolio of clinical-stage and preclinical neuroscience assets that include PR001 for patients with Parkinson's disease with GBA1 mutations and neuronopathic Gaucher disease, PR006 for patients with frontotemporal dementia with GRN mutations, PR004 for patients with specific synucleinopathies, and possible gene therapies targeted at Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other neurodegenerative disorders, Lilly said in a Dec. 15, 2020 company press release. With Prevail’s pipeline, Lilly will work to create a new gene therapy program.

"We are pleased to complete the acquisition of Prevail and establish a gene therapy program at Lilly that has the potential to deliver transformative treatments for patients with neurodegenerative diseases such as Parkinson's, Gaucher, and dementia," said Mark Mintun, MD, vice president of pain and neurodegeneration research at Lilly, in a Jan. 22, 2021 company press release.

https://investor.lilly.com/news-releases/news-release-details/lilly-announces-agreement-acquire-prevail-therapeutics

https://investor.lilly.com/news-releases/news-release-details/lilly-completes-acquisition-prevail-therapeutics

Through the acquisition, Lilly will have access to Prevail’s portfolio of clinical-stage and preclinical neuroscience assets.

Eli Lilly Completes $1.5 Billion Acquisition of Prevail Therapeutics

On Jan. 20, 2021, Janet Woodcock, MD announced in a 

 to FDA staff members that she will serve as acting commissioner of FDA, taking over for Stephen Hahn, FDA’s previous acting commissioner.

Woodcock joined FDA in 1986 and has held several positions, including deputy commissioner and chief medical officer, deputy commissioner for operations, chief operating officer for the commissioner’s office, and director of the Center for Drug Evaluation and Research (CDER).

“I know you all have endured hardships while carrying out our public health mission, balancing work and family, and trying to stay safe. It has not gone unnoticed,” she wrote in her note. “I believe life will improve in 2021, but I don’t know how quickly that will happen. The hope keeps me going. I look forward to working with you to achieve our vital public health mission, and with our HHS [Department of Health and Human Services] partners and The White House during this transitional period.”

Woodcock will serve as acting commissioner of FDA, taking over for Stephen Hahn, FDA’s previous acting commissioner. 

Janet Woodcock to Serve as Acting Commissioner of FDA

Grifols, a Spanish pharmaceutical and chemical manufacturer, announced on Jan. 18, 2021 that it has initiated a clinical trial in Spain to evaluate a new COVID-19 drug based on its immunoglobulin, Gamunex-C, and antibodies from plasma donors who have recovered from the disease.

According to a company press release, the drug offers immediate post-exposure protection against the virus and will serve as a counterpart to the vaccine during its early phases. Additionally, the new drug has the potential to contain COVID-19 outbreaks in areas where vaccination measures haven’t started or are still underway.

“[The drug] is easy to refrigerate while its subcutaneous administration facilitates its distribution and use in any doctor’s office, avoiding hospitalization,” said Dr. Antonio Páez, medical director at Grifols, in the press release. “If the new therapy’s efficacy is confirmed, it could be administered to people who test positive for the virus through PCR and antigen tests in hospitals and primary care offices.”

The drug offers immediate post-exposure protection against the virus and will serve as a counterpart to the vaccine during its early phases.

Grifols Initiates Trial for New COVID-19 Drug

Merck, known as MSD outside the United States and Canada, announced on Jan. 20, 2021 that FDA has approved Verquvo, its soluble guanylate cyclase stimulator for the reduction of the risk of cardiovascular death and heart failure hospitalization in adults with symptomatic chronic heart failure.

The approval was based on positive data from a randomized, parallel-group, placebo-controlled, double-blind, event-driven, multi-center trial that compared the drug to a placebo in more than 5000 participants with symptomatic chronic heart failure, Merck said in a company press release. Verquvo proved to be more effective than the placebo in reducing the risk of cardiovascular death or heart failure hospitalization based on a time-to-event analysis.

“Verquvo has been shown to reduce the risk of cardiovascular death and heart failure hospitalization following a hospitalization for heart failure or need for outpatient IV [intravenous] diuretics. We are pleased to offer a meaningful new treatment option for appropriate patients with symptomatic chronic heart failure,” said Dr. Roy Baynes, senior vice-president and head of global clinical development, chief medical officer, Merck Research Laboratories, in the press release. “This approval builds upon Merck’s proud history of developing therapies for the treatment of patients with cardiovascular disease.”

Verquvo is a soluble guanylate cyclase stimulator for the reduction of the risk of cardiovascular death and heart failure hospitalization in adults with symptomatic chronic heart failure. 

FDA Approves Merck’s Symptomatic Heart Failure Drug

AstraZeneca and Daiichi Sankyo announced on Jan. 20, 2021 that their HER2-positive metastatic breast cancer treatment, Enhertu (trastuzumab deruxtecan), has been granted conditional approval from the European Commission as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more previous anti-HER2-based regimens.

The approval was based on positive results from a single-arm Phase II trial where the treatment demonstrated significant antitumor activities in patients with the disease, AstraZeneca said in a company press release. The treatment was previously approved for use in the United States under accelerated approval, and in Japan under a conditional early approval system.

“Enhertu is already transforming outcomes for patients with HER2-positive metastatic breast cancer in the US and Japan, and this approval enables us to bring the benefits of this medicine to patients in the [European Union],” said Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca. “We will continue to explore the potential of Enhertu in this setting, as well as in earlier lines of treatment and stages of disease, with the ambition of improving the lives of patients with HER2-targetable breast cancer.”

“This expedited review underscores the practice-changing potential of Enhertu for patients in the metastatic setting,” added Gilles Gallant, senior vice president, global head, Oncology Development, Oncology R&D, Daiichi Sankyo, in the press release. “Enhertu is the first-ever new medicine to be approved in breast cancer in Europe on the basis of Phase II single-arm data, and one of the fastest accelerated assessment procedures for an application in oncology.”

The approval was based on positive results from a single-arm Phase II trial where the treatment demonstrated significant antitumor activities in patients with the disease.

AstraZeneca and Daiichi Sankyo’s Breast Cancer Treatment Approved for Use in Europe

Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company, and Merus, a Netherlands-based clinical-stage oncology company, announced on Jan. 19, 2021 that they are entering into a research collaboration and exclusive license agreement to research and develop up to three CD3-engaging T-cell redirecting bispecific antibody therapies using Merus' proprietary Biclonics platform for up to $1.6 billion.

Through the agreement, Merus will receive an upfront cash payment of $40 million, an equity investment by Lilly of $20 million, and $540 million in potential development and commercialization milestones per product, Eli Lilly said in a company press release. Merus will handle the discovery and early-stage research activities of the products, while Loxo Oncology at Lilly will lead additional research, development, and commercialization activities.

"CD3-engaging bispecific antibodies are rapidly becoming one of the most transformative immune-modulating modalities used to treat cancer. We expect these therapies will become an important component of the Loxo Oncology at Lilly biologics strategy," said Jacob Van Naarden, chief operating officer of Loxo Oncology at Lilly, in the press release. "Merus has built a differentiated platform and one that we believe can enable us to create bispecific antibody therapies with wider therapeutic indexes than those available today. We look forward to working closely with Merus to develop new potential medicines for patients with cancer."

"The collaboration with Loxo Oncology at Lilly and their world class research capabilities opens up exciting possibilities for Merus' Biclonics platform," added Bill Lundberg, MD, president and CEO at Merus, in the press release. "Our CD3 T-cell engager platform includes over 175 novel and diverse anti-CD3 common light chain antibodies across a wide range of affinities and attributes and enables functional screening of large libraries for optimal performance. We look forward to working together with Loxo Oncology at Lilly to define a new generation of medicines to treat cancer."

The companies will develop up to three CD3-engaging T-cell redirecting bispecific antibody therapies using Merus' proprietary Biclonics platform.

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