Feliza Mirasol is the science editor for 

Feliza Mirasol

Nexcella, a subsidiary of US-based Immix Biopharma and a clinical-stage biopharmaceutical company, announced on May 26, 2023 that it has begun producing engineering batches of NXC-201, its lead candidate and a chimeric antigen receptor T cell (CAR-T) therapy, at its US manufacturing site.

These engineering batches are intended to support the company’s planned expansion into the United States of an ongoing Phase Ib/IIa clinical study (NEXICART-1 [NCT04720313]) in adults with relapsed or refractory multiple myeloma and amyloid light chain (AL) amyloidosis. NXC-201 is a novel B-cell maturation antigen (BCMA)-targeted CAR-T cell therapy. The commencement of these engineering batches represents a crucial next step in transferring Nexcella’s existing CAR-T good manufacturing practice manufacturing process to the US, according to a company press release.

“We are working tirelessly to bring NXC-201 to US patients,” said Ilya Rachman, executive chairman of Nexcella, in the press release. “NXC-201 is the first CAR-T being developed in AL amyloidosis, and in multiple myeloma, patients face significant obstacles when seeking BCMA-targeted CAR-T treatments [such as] NXC-201. We look forward to continuing to advance NXC-201 as we work to improve treatment outcomes for patients in the US suffering from AL amyloidosis and multiple myeloma.”

“Today, 95% of US medical centers are unable to offer CAR-T cell therapy,” said Gabriel Morris, president of Nexcella, in the release. “NXC-201 has already been trialed in over 50 patients, demonstrating a [one to two]-day median short side-effect duration, which offers potential to become the first out-patient CAR-T, potentially reducing hospitalization costs up to 80% and enabling dosing in 95% of US medical centers today unable to offer CAR-T cell therapy.”

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The start of production of US engineering batches of NXC-201, a CAR-T cell therapy candidate in early clinical development, is the first step in transferring Nexcella’s existing manufacturing process to the United States.

Nexcella Begins Production of CAR-T Cell Therapy Engineering Batches at US Manufacturing Site

On May 30, 2023, Olon Group, a global API supplier, announced that it has begun construction of a new manufacturing facility at its Rodano site in Milan, Italy, which will be wholly dedicated to managing and producing ultra-potent compounds. These compounds are intended for use as payloads and payload-linkers for antibody-drug conjugates (ADCs).

Olon has invested €22 million (US$23 million) into the new facility, which will house an ultra-high-containment production line to produce high-potency and toxic products. The facility is expected to reach containment level occupational exposure band 6 (i.e., target occupational exposure limit 10 ng/m3).

The first phase of construction will involve the building of the payload research and development area, which is expected to be complete by the first half of 2024. The second phase will involve finalizing the production line by creating quality control and good manufacturing practice production areas.

Upon completion of construction, the new facility will house production, quality control, and R&D areas as well as auxiliary facilities, forming a complete, closed-loop system. This closed-loop system will include all steps of the ultra-potent compound production process—synthesis, isolation, drying, and analysis—all within an ultra-high-containment plant, according to a company press release.

“[A]bout 80% of the ADCs either approved or under development contains [these] type[s] of payload[s], such as dolastatins or maytansnoids, and there are also other highly strategic classes of cytotoxic payloads, such as anthracyclines, camptothecin, and calicheamicin,” said Giorgio Bertolini, senior vice-president R&D, Olon Group, in the release.

API supplier Olon has started construction of a new manufacturing facility in Milan, Italy, which will be dedicated to production of cytotoxic payloads and linkers for ADCs.

Olon Makes Headway into ADCs Market with New Manufacturing Facility in Italy

Sandoz, a Novartis division specializing in off-patent (generic and biosimilar) therapeutics, announced on May 25, 2023 that the European Medicines Agency (EMA) has accepted its two marketing authorization applications (MAAs) for a proposed biosimilar to denosumab. Denosumab is indicated for treating osteoporosis in postmenopausal women, preventing skeletal-related complications in cancer that has spread to the bone, and treating unresectable giant cell tumor of the bone, according to a company press release.

Sandoz’s two MAAs include all indications covered by the reference biologics, Amgen’s Prolia (denosumab) and Xgeva (denosumab), respectively. The indications include treating osteoporosis in postmenopausal women and in men at increased risk of fractures, treatment-induced bone loss, prevention of skeletal- related complications in cancer that have spread to the bone, and giant cell tumor of the bone.

The applications include a comprehensive analytical and clinical data package, which comprises data from a Phase I pharmacokinetic/pharmacodynamic (PK/PD) similarity study in healthy volunteers and an integrated Phase I/III study (ROSALIA). According to the data package, Sandoz’s denosumab biosimilar matches the reference biologic in relation to PK, PD, efficacy, safety, and immunogenicity in the respective populations used in the studies. The data also contribute to the demonstration of similarity, which forms the basis for the biosimilar’s use in all indications for which Xgeva and Prolia are approved, according to the press release.

“Sandoz is one of the first to have its applications for a proposed biosimilar denosumab accepted by the EMA. If approved, this has the potential to provide people living with osteoporosis and cancer of the bone or bone metastasis access to a cost-effective and high-quality treatment option,” said Florian Bieber, development platform head Biopharmaceuticals and chief medical officer, Sandoz, in the press release. “This news follows the recent application acceptance by [FDA] and supports our continued commitment to providing expanded access to life-changing treatments, while also helping over-burdened healthcare systems generate savings.”

Sandoz’s marketing authorization applications for a proposed biosimilar to denosumab are supported by a comprehensive analytical and clinical data package.

EMA Accepts MAAs from Sandoz for Proposed Denosumab Biosimilar

FDA announced on May 19, 2023 that it granted approval to Krystal Biotech, a US-based biotechnology company focused on genetic medicines for rare diseases, for the company’s product, Vyjuvek (beremagene geperpavec-svdt), a herpes-simplex virus type 1 (HSV-1) vector-based gene therapy. The indication is for treating wounds in patients six months of age and older who have dystrophic epidermolysis bullosa (DEB) with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene. According to an agency press release, Vyjuvek is the first topical gene therapy approved for this indication.

DEB is a genetic disorder affecting the connective tissue in the skin and nails. It is caused by mutation(s) in the COL7A1 gene, which encodes type VII collagen (COL7), an essential protein that helps strengthen and stabilize the outer and middle layers of the skin, according to the agency’s press release. A COL7A1 deficiency leads to separation of skin layers, which causes painful and debilitating blisters and wounds. The disorder usually shows at birth and is divided into two major types depending on the inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB).

Symptoms can vary. Individuals with DDEB typically experience mild cases; blistering primarily affects the hands, feet, knees, and elbows. In comparison, RDEB cases can be painful and debilitating, and often involves widespread blistering that can lead to vision loss, disfigurement, and other serious medical complications that can be fatal, according to the FDA press release.

Vyjuvek is a genetically modified herpes-simplex virus that is used to deliver normal copies of the COL7A1 gene to the wounds, which then helps to hold the layers of skin together, maintaining the integrity of the skin. The FDA release reports that Vyjuvek has also been modified such that it cannot replicate in normal cells. According to clinical study results, 65% of Vyjuvek-treated wounds completely closed compared to only 26% complete-wound-closure in placebo-treated subjects.

“Vyjuvek is the first FDA-approved gene therapy treatment for DEB, a rare and serious genetic skin disorder,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, in the release. “Today’s action demonstrates [FDA]’s ongoing commitment to supporting the development and evaluation of new treatments that address unmet needs for rare diseases or conditions.”

FDA has approved the first topical gene therapy product for treating wounds in patients with dystrophic epidermolysis bullosa.

FDA Approves Topical Gene Therapy for Treating Wounds Associated with Rare Genetic Skin Disorder

AbbVie announced on May 19, 2023 that FDA has approved EPKINLY (epcoritamab-bysp), a T-cell engaging bispecific antibody for treating relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The bispecific is particularly indicated for treating adult patients with R/R DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma and high-grade B–cell lymphoma (HGBL). Administration of the bispecific is intended for patients who have already had two or more lines of systemic therapies.

According to a company press release, DLBCL patients are typically treated with chemoimmunotherapy-based regimens, but several targeted therapies, including T-cell mediated treatments, have recently emerged for R/R patients. A single agent and ready-available or off-the-shelf treatment options, however, remain limited.

"DLBCL is an aggressive cancer type that can rapidly progress and resist treatment. The FDA approval of EPKINLY represents a new treatment mechanism of action for third-line DLBCL patients,” said Thomas Hudson, senior vice-president, research and development, chief scientific officer, AbbVie, in the press release. “As a non-chemotherapy, single-agent treatment for DLBCL patients, we hope that [epcoritamab-bysp] can effectively treat this aggressive cancer type and can be used for patient care quickly and in an off the shelf form for physicians."

"Patients with DLBCL who relapse or are refractory to currently available therapies have limited options. Generally, the prognosis for these patients is poor and management of this aggressive disease can be challenging," said Tycel Phillips, City of Hope associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, in the release. "Epcoritamab is a subcutaneous bispecific antibody that offers an additional treatment option for this patient population. With this approval, patients who are in need of additional therapy may have the opportunity to receive epcoritamab after failure to respond or relapse after two or more systemic therapies."

AbbVie co-developed epcoritamab-bysp with partner Genmab as part of an oncology collaboration between the companies.

FDA has approved AbbVie’s EPKINLY (epcoritamab-bysp), a bispecific antibody for treating relapsed or refractory diffuse large B-cell lymphoma.

FDA Approves AbbVie’s Bispecific Antibody for Treating Lymphoma

Mustang Bio, a US-based clinical-stage biopharmaceutical company, announced on May 18, 2023 that it has entered into an agreement with uBriGene Biosciences, the US subsidiary of uBriGene Group, a China-based cell and gene therapy (CGT) contract development and manufacturing organization (CDMO). According to the terms, uBriGene will acquire Mustang Bio’s commercial-scale CGT development, manufacturing, and analytical testing facility in Worcester, Mass.

Under the agreement, uBriGene will acquire the Worcester facility for a total consideration of $11 million, which includes a $6 million upfront payment plus an additional $5 million payable upon Mustang raising $10 million in equity after the close of transaction. The transaction is expected to close in June 2023 dependent on closing conditions.

Also under the agreement, and subject to closing, uBriGene and Mustang will enter into a manufacturing supply agreement, under which uBriGene will manufacture Mustang’s lead product candidates. According to a uBriGene company press release, uBriGene will also take over the clinical manufacturing of MB-106, Mustang’s chimeric antigen receptor T cell (CAR-T cell) therapy for treating a wide range of hematologic malignancies, including Waldenstrom macroglobulinemia, a rare malignant disorder of the bone marrow and lymphatic tissues. According to a Mustang company press release, uBriGene will continue to support MB-106 manufacturing for the duration of an ongoing multi-center Phase I/II trial.

 current good manufacturing practice-compliant facility that supports process development, manufacturing, and analytical testing of CGTs. It is designed to be flexible and to expand and support various CGT production requirements and capacities. uBriGene intends to expand the site’s capabilities to manufacture a broader portfolio of advanced modalities with the help of Mustang’s experienced staff and robust quality and operating systems. According to Mustang’s company press release, uBriGene will also offer its expertise in preclinical research services and late-stage and commercial manufacturing of advanced therapy products; in particular, uBriGene will bring to bear its expertise in product and process characterization as well as regulatory inspections.

“We are very pleased to have found a great partner for the manufacturing of our CAR-T cell and gene therapies, and we believe that this strategic partnership with uBriGene will meet our portfolio manufacturing needs to reach critical upcoming data inflection points, while extending our cash runway. I want to thank our manufacturing team for their dedication in building and growing our Worcester facility since it opened in 2018. While we are optimizing our resources at Mustang, we look forward to continuing to work with many of our colleagues in this new capacity, as our CDMO,” said Manuel Litchman, president and CEO of Mustang, in that company’s press release.

“This acquisition is important to uBriGene’s commitment to support the development, clinical, and commercial supply of cell and gene therapies to sustain industry demand and provide new CDMO options,” said Alex Chen, president of uBriGene, also in the Mustang release. “We look forward to working together with the University of Massachusetts Chan Medical School and local biotechnology companies to continue to advance the manufacturing ecosystem in the Greater Boston region. This partnership enables us to expand rapidly to create a North American presence and offer the same high-quality cell and gene therapy development and manufacturing capabilities for the U[nited] S[tates] that we currently provide in Asia, including to support Mustang Bio’s lead clinical-stage CAR-T program.”

uBriGene Biosciences will acquire Mustang Bio’s Worcester, Mass., CGT manufacturing facility in a deal worth up to $11 million, expanding its operations into the US market.