Pharmaceutical Technology Editors

Sanofi announced on June 28, 2022 that the European Commission (EC) has approved Xenpozyme (olipudase alfa) as the first enzyme replacement therapy for the treatment of Acid Sphingomyelinase Deficiency (ADMS). The European Medicines Agency (EMA) granted the treatment PRIME designation due to the urgent unmet medical needs of the ASMD community.

ASMD is a rare, progressive genetic disease with significant morbidity and mortality, especially among infants and children. Many pediatric patients with the disease do not survive to adulthood. ASMD symptoms may manifest as enlarged spleen or liver, difficulty breathing, lung infections, and unusual bruising or bleeding. Supportive care is the only current option to aid in managing the symptoms of the disease.

Xenpozyme is an enzyme replacement therapy that is designed to replace deficient or defective acid sphingomyelinase (ASM), an enzyme that allows for the breakdown of lipid sphingomyelin. ASMD can lead to lifelong damage to multiple organs due to the insufficient amount of the ASM enzyme.

“The ASMD community has waited many years for a treatment for this rare and debilitating genetic disease,” said John Reed, MD, PhD, executive vice president and global head of research and development at Sanofi, in a press release. “The approval of Xenpozyme by the European Commission represents a transformational shift in what we can offer to patients, demonstrated by the clinically important improvements across major manifestations of ASMD and the sustained effects noted over longer term treatment.”

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The European Commission has approved Xenpozyme as the first treatment for ASMD.

Xenpozyme Approved by EC for the Treatment of ASMD

FDA unveiled its Action Plan for Rare Neurodegenerative Diseases including Amyotrophic Lateral Sclerosis (ALS) on June 23, 2022. The plan is a five-year strategy for improving and extending the lives of people living with rare neurodegenerative diseases through advancing the development of, and improving patient access to, safer and more effective medical treatments and products.

The action plan outlines how FDA will move forward in addressing challenges in drug development for rare neurodegenerative diseases. FDA will take actions such as regulatory science initiatives, enhancements to existing programs, and new policy initiatives. The plan was developed in accordance with the Accelerating Access to Critical Therapies for ALS Act, which was signed into law on December 23, 2021.

“The effects of rare neurodegenerative diseases are devastating, with very few effective therapeutic options available to patients. We recognize the urgent need for new treatments that can both improve and extend the lives of people diagnosed with these diseases,” said FDA commissioner Robert M. Califf, MD, in a press release. “To face that challenge and to accelerate drug development, we need innovative approaches to better understand these diseases while also building on current scientific and research capabilities. This action plan, especially including the use of public-private partnerships and direct involvement of patients, will ensure the FDA is working toward meeting the task set forth by Congress to enhance the quality of life for those suffering by facilitating access to new therapies.”

The action plan will span over five years and will fulfill a requirement of the Accelerating Access to Critical Therapies for ALS Act.

FDA Releases Action Plan for Rare Neurodegenerative Diseases

On June 27, 2022, MilliporeSigma, the US and Canada Life Science business of Merck KGaA, Darmstadt, Germany, announced the launch of the BioContinuum Seed Train Platform, which enables biomanufacturers to use seed train intensification in upstream bioprocessing. The company launched the product at the European Society for Animal Cell Technology meeting held in Lisbon, Portugal on June 26–June 29, 2022.

The platform contains proprietary products for N-1 perfusion and high cell density cryopreservation (HCDC), including the off-the-shelf medium, Cellvento 4CHO-X Expansion Medium, which is specifically designed for seed train expansion and N-1 perfusion; the Cellicon Perfusion Solution for enhanced cell retention; and closed processing-ready Mobius HCDC R&D single-use assemblies for high cell density cryopreservation.

The BioContinuum Seed Train Platform is an integrated platform that addresses the need for an efficient, consistent seed train that supports increased cell densities for intensification of the N production process. The platform specifically enables increased monoclonal antibody productivity, reduces facility footprint and utilization, and aims to accelerate manufacturing timelines. The platform offers a full closed intensification process, which significantly reduces the risk of contamination.

MilliporeSigma’s new BioContinuum Seed Train Platform offering enables a fully closed bioprocessing environment for both fed-batch and perfusion N-production.

MilliporeSigma Intensifies Upstream Processing with New BioContinuum Seed Train Platform Offering

ImmunoGen entered into a multi-year collaboration with Oxford BioTherapeutics (OBT), a clinical-stage oncology company, to research novel, first-in-class antibody-drug conjugates (ADCs). According to a June 13, 2022 company press release, the companies will direct ImmunoGen's proprietary linker-payload technology at novel targets identified using OBT's proprietary drug discovery platform, OGAP. The companies will support these R&D efforts through joint funding and by using their respective proprietary technologies.

Under the agreement, OBT will receive an upfront payment from ImmunoGen. The deal will include preclinical programs that OBT is developing. When OBT-generated antibodies have been coupled with ImmunoGen's proprietary linker-payload technology, each company can select one or more development programs to further develop on its own. Each company will be eligible to receive milestone payments dependent on pre-specified development and regulatory milestones as well as tiered royalties as a percentage of worldwide commercial sales, with respect to each program selected by the other company. Each company will be solely responsible for all R&D costs associated with the specific program of its choosing.

"OBT has demonstrated expertise in identifying novel targets for the development of specific antibodies—two key components to generating successful ADCs," said Stacy Coen, ImmunoGen's senior vice-president and chief business officer, in the company press release. "This expertise, combined with ImmunoGen's portfolio of cancer-killing payloads and linkers, will be instrumental as both companies work to develop novel ADCs designed to address cancers with high unmet need. We look forward to working with OBT as we expand and diversify our investment in ADC research capabilities, deepen our pipeline, and transition to a fully-integrated oncology company."

"[ImmunoGen’s] expertise, in combination with the unique targets from our OGAP database, provides potential to strengthen our respective drug pipelines with novel and highly differentiated ADCs for cancer patients in need of novel therapeutic options," said Christian Rohlff, CEO of Oxford BioTherapeutics, in the release.

ImmunoGen has formed a research collaboration with Oxford BioTherapeutics to develop novel antibody-drug conjugates for cancers with high unmet needs.

ImmunoGen Partners with Oxford BioTherapeutics to Develop Novel ADCs

Sanofi and GSK announced positive data from their vaccine trial evaluating an adjuvanted bivalent COVID-19 vaccine candidate on June 24, 2022. Designed for the D614 and Beta (B.1.351) variations, the Sanofi-GSK vaccine is the first candidate to demonstrate efficacy in a placebo-controlled trial with a high Omicron variant circulation.

The data comes from stage two of the Phase III COVID-19 vaccine trial VAT08, which was composed of more than 13,000 participants ages 18 or older. The Sanofi-GSK Beta-containing vaccine candidate demonstrated a 64.7% efficacy against symptomatic COVID-19 and 72% efficacy in Omicron-confirmed symptomatic cases. In previously seropositive populations, the efficacy was 75.1% against symptomatic infection and 93.2% in Omicron-confirmed symptomatic cases, according to the sequencing analysis performed to date. Thus far, sequencing has been performed for 71 out of 121 total cases.

“Today’s results reinforce the strong potential for the Beta antigen to confer broad protection against multiple strains that cause COVID-19,” said Thomas Triomphe, executive VP, vaccines, Sanofi, in a company press release. “With the immunogenicity data from our Beta-booster vaccine, they support our belief that, in a largely seropositive world, a next-generation Beta booster vaccine could provide protection against variants like Omicron.”

According to the press release, the vaccine candidate showed a favorable safety and tolerability profile. The companies plan to submit the data to regulatory authorities to indicate the potential for Sanofi-GSK’s Beta-based vaccine candidate as a relevant response to public health needs.

The Sanofi-GSK vaccine is the first candidate to demonstrate efficacy in a placebo-controlled trial with a high-Omicron environment.

First Successful Efficacy Study Against Omicron With COVID-19 Vaccine

Lonza announced that it has entered into a manufacturing agreement with Pierre Fabre on June 15, 2022. Lonza will provide Pierre Fabre with drug product manufacturing services for clinical supply from its fill/finish facility in Stein, Switzerland.

According to a company press release, the collaboration is aimed at manufacturing W0180, a monoclonal antibody (mAb) that is currently being investigated as a single agent and in combination with pembrolizumab in various solid tumors. It targets the V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA), a negative checkpoint regulator of T-cell response that is expressed in the tumor microenvironment. The mAb is currently in a Phase I clinical trial.

"The W0180 will be manufactured in Lonza's GS Xceed Expression CHO [Chinese hamster ovary] System, also successfully used for the IGF1R [insulinlike growth factor1 receptor] and cMet antibodies discovered by Pierre Fabre," said Jean-Luc Lowinksi, CEO, Pierre Fabre Medical Care.

Lonza will produce drug product for Pierre Fabre’s monoclonal antibody W0180.