Pharmaceutical Technology Editors

In a Sept. 7, 2021, letter, the Coalition for Epidemic Preparedness Innovations (CEPI) stated that developing the next generation of COVID-19 vaccines will only be possible if comparator vaccines—COVID-19 vaccines that have already been approved—are available for clinical trials. This next generation of vaccines need to address global supply and variants, and there is a growing need to compare efficacy of the comparator vaccines to the COVID-19 vaccine candidates.

The approval of COVID-19 vaccines has thus far been based on data from seronegative populations in placebo-controlled vaccine efficacy trials, according to CEPI. But these trials are difficult to conduct due to the rise in the number of people vaccinated or who previously had COVID-19. Therefore, CEPI states that comparator vaccines need to be used in trials of new vaccine candidates to replace placebos. Using comparator vaccines would also support comparing efficacy and immunobridging trials for registration of new vaccine candidates.

But the lack of access to comparator vaccines is a challenge, which stalls the development of vaccine candidates. CEPI encourages governments and vaccine manufacturers to broaden supply contracts to provide access to the comparator vaccines for these trials and to ultimately develop new vaccines.

The Coalition for Epidemic Preparedness Innovations (CEPI)

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The Coalition for Epidemic Preparedness Innovations stated that developing the next generation of COVID-19 vaccines will only be possible if comparator vaccines are available for clinical trials.

CEPI Says Approved COVID-19 Vaccines Must Be Available for Clinical Trials

Moderna announced on Sept. 9, 2021, that the company will develop a single-dose vaccine, the mRNA-1073, which is designed as a booster for both COVID-19 and the flu. Additionally, they announced the mRNA-1365 development candidate, a pediatric vaccine designed to fight syncytial virus and human metapneumovirus.

The announcement was part of an overview provided to investors at their virtual R&D day, which discussed programs they currently have in development. Other projects that were discussed include an Epstein-Barr virus prophylactic vaccine and a personalized cancer vaccine.

“Today we are announcing the first step in our novel respiratory vaccine program with the development of a single-dose vaccine that combines a booster against COVID-19 and a booster against flu,” said Stéphane Bancel, CEO of Moderna, in a company press release. “We are making progress on enrolling patients in our rare disease programs, and we are fully enrolled in our personalized cancer vaccine trial. We believe this is just the beginning of a new age of information-based medicines.”

Discussions have been swirling about the necessity of COVID-19 booster shots. The US Department of Human Health & Services 

 that they felt booster shots would soon become necessary. Others, such as 

 director-general, World Health Organization, felt it was more pressing to get initial vaccine doses to countries with minimal vaccine exposure.

Moderna’s new single-dose vaccine will be a booster for both COVID-19 and the flu.

Moderna to Develop Combined COVID-19/Flu Vaccine

BioMarin Pharmaceutical announced in a Sept. 5, 2021, press release that FDA placed a clinical hold on the BMN 307 Phearless Phase I/II study. The study was evaluating BMN 307, an investigational AAV5-phenylalanine hydroxylase (PAH) gene therapy, in adults with phenylketonuria (PKU).

The clinical hold was based on interim safety findings from a pre-clinical, non-GLP pharmacology study. Tumors developed in some of the mice receiving the highest dose of BMN 307 with evidence for integration of portions of AAV vector into the genome.

The pre-clinical study was to determine the durability of BMN 307 activity in mice with two germline mutations, which may predispose the mice to the development of malignancy. One mutation eliminated the PAH gene missing in PKU, and the second rendered the animals immunodeficient.

Of the 63 animals that were treated, six of seven animals that received the highest dose of BMN 307 (2e14 Vg/kg) had tumors on liver necropsy 52 weeks after dosing with evidence for integration of portions of AAV vector into the genome. No lesions were observed in any mice at 24 weeks. Five mice had adenomas and one had a hepatocellular carcinoma. The translatability of these findings to humans is uncertain and under further investigation.

To date, BioMarin has dosed humans in the Phearless Phase I/II clinical study with lower doses of either 2e13 vg/kg or 6e13 vg/kg. The liver health of Phearless study participants is regularly monitored. The company said it will work with the data review board and principal investigators to further evaluate the study participants who received BMN 307 and will continue to monitor them over the long-term.

"More than 3,000 patients have been treated with gene therapy, and there are no reports of cancers emerging as a consequence. Acknowledging the complexity of the issue as highlighted in this week's FDA discussion, integrational mutagenesis and resultant cancer formation has been observed in mice using other AAV vectors," said Hank Fuchs, president of worldwide research and development at BioMarin, in a company press release. "Therefore, we plan to investigate these findings. For patients who have already received lower doses of these vectors, we will continue to carefully evaluate and monitor their health. We are committed to understand and mitigate any risk of cancer causation."

BioMarin has paused further enrollment of additional participants outside the United States in Phearless Phase I/II study and are working with FDA and other health authorities. In the company press release, they said they will communicate next steps when available.

FDA placed a clinical hold on the BMN 307 Phearless Phase I/II study, which was evaluating an investigational PAH gene therapy in adults with PKU.

FDA Places Clinical Hold on BioMarin’s Phase I/II Gene Therapy Study

Thermo Fisher Scientific announced on Sept. 8, 2021 plans to establish a dedicated single-use technologies (SUT) product manufacturing facility in Nashville, Tenn. The facility, which is expected to begin construction by the second quarter of 2022, will more than double the company’s current SUT manufacturing capacity.

The Nashville site is part of a more than $650 million investment into bioprocessing production capabilities expansions, which are set to take place across 11 manufacturing sites in North America, Europe, and Asia. The investment also includes expansion projects in Logan, Utah, and Suzhou, China, along with a new SUT manufacturing site in Singapore.

The $650 million investment program also expands global production capabilities in additional bioprocessing manufacturing networks. Capacity expansion projects in Grand Island, NY, Miami, Fla., and Inchinnan, Scotland, will increase production of cell culture media (Gibco), supplements, and process liquids, as well as the manufacturing of customer-owned proprietary media formulations.

"Over the last few years, more and more biological drugs and vaccines are being manufactured utilizing the single-use platform. This has created incredible demand for our SUT products," said Michel Lagarde, executive vice-president of Thermo Fisher Scientific, in a company press release. "The site in Nashville will be critical in Thermo Fisher's global network to continue to support the biopharma industry's work in developing life-saving biologics and vaccines."

Thermo Fisher Scientific plans to expand its Nashville, Tenn., site by establishing a dedicated single-use technology manufacturing facility at the site, doubling capacity. 

Thermo Fisher to Establish Single-Use Technology Site in US

Impel NeuroPharma, a biopharmaceutical company, announced on Sept. 3, 2021, that FDA approved Trudhesa (dihydroergotamine mesylate) nasal spray for acute treatment of adults with or without aura.

Trudhesa delivers dihydroergotamine mesylate (DRE) to the bloodstream through the nasal space. Because the nasal passage is vascular-rich, this is intended to offer rapid symptom relief even if it is administered hours after the onset of a migraine without the need for an injection or infusion, according to a company press release.

This approval comes on the heels of a Phase III, open-label, pivotal safety study, with the primary objective of assessing the safety and tolerability of Trudhesa. Over 5650 migraine attacks were treated over 24 or 52 weeks during the study. According to the press release, the results found that it was generally well tolerated, while exploratory efficacy findings showed it provided rapid, sustained, and consistent symptom relief.

“We are delighted with the approval of Trudhesa and are proud to offer the millions of Americans with migraine a non-oral, acute treatment option that may provide rapid, sustained, and consistent relief, even when taken late into a migraine attack,” said Adrian Adams, chairman and CEO of Impel NeuroPharma, in the press release. “The approval of Trudhesa marks the culmination of more than a decade of research and advanced engineering to pair the proven efficacy of DHE with our innovative [Precision Olfactory Delivery] POD technology.”

Impel Neuropharma’s Trudhesa, a nasal spray, received FDA approval for treating migraines in adults with and without aura.

Impel NeuroPharma Gets FDA Approval for Nasal Spray Migraine Treatment

On Sept. 7, 2021, The Center for Drug Evaluation and Research (CDER) launched the voluntary Novel Excipient Review Pilot Program, which is designed to give an opportunity to excipient manufacturers to obtain FDA review on certain novel excipients prior to their use in drug formulations.

The program will be initially available for excipients that meet two criteria: they must not have been previously used in FDA-approved products, and they cannot have an established use in food. If an excipient meets these requirements, it can enter the two-stage approval process.

The first stage requires manufacturers to provide a thorough overview of their novel excipients. This includes a description, its proposed use, and the public health or drug development need addressed by their excipient. Factors such as potential public health benefit and novel drug development potential will be considered at this stage.

Of all submissions, CDER intends to accept approximately four initial proposals, but more may be considered as resources allow. If accepted, the second stage consists of providing a full data package consisting of toxicology and quality data.

If interested, applicants should send their proposals to Novel-Excipient-Program@fda.hhs.gov by Dec. 7th, 2021. For a comprehensive breakdown of the application procedure, an outline can be found below “Resources” on the 

The Novel Excipient Review Pilot Program will allow excipient manufacturers to obtain FDA review of certain novel excipients prior to use in drug formulations.