Feliza Mirasol is the science editor for 

Feliza Mirasol

GSK's application for expanding the use of Jemperli (dostarlimab) in combination with standard-of-care chemotherapy (carboplatin and paclitaxel) has been accepted by the European Medicines Agency (EMA). GSK is seeking approval for the combination therapy for treating all adult patients with primary advanced or recurrent endometrial cancer. The EMA’s Committee for Medicinal Products for Human Use is expected to begin formal review process to make a recommendation to the European Commission, with approval expected in the first half of 2025, according to a June 24, 2024 GSK company press release.

In the European Union (EU), Jemperli in combination with carboplatin and paclitaxel is currently approved for treating adult patients who are candidates for systemic therapy with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H). If approved under the new application, dostarlimab would be expanded to treating all patients with primary advanced or recurrent endometrial cancer. Treatment would be administered regardless of the patients’ biomarker type, including those with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors, where currently no approved frontline immuno-therapy-based treatments are available in the EU, according to GSK in the press release.

GSK’s application is based on results from Part 1 of a Phase III trial (RUBY), in which the primary endpoint was met—investigator-assessed progression-free survival and overall survival (OS), which demonstrated a statistically significant and clinically meaningful benefit in the overall patient population treated with dostarlimab plus carboplatin-paclitaxel compared to chemotherapy alone. According to the company press release, this trial is the only clinical trial that has shown a statistically significant OS benefit in this patient population. “The safety and tolerability analyses from RUBY showed a safety profile for dostarlimab plus carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents,” GSK stated in the release.

Endometrial cancer is found in the endometrium (inner lining of the uterus) and is the most common gynecologic cancer in developed countries. Approximately 417,000 new cases are reported each year worldwide (1) with incidence rates expected to increase by almost 40% between 2020 and 2040 (2,3). Approximately 121,000 people are estimated to be diagnosed with primary advanced or recurrent endometrial cancer yearly in Europe (4).

Jemperli, which was discovered by AnaptysBio, was licensed to TESARO in March 2014 (5); in December 2018, GSK announced its acquisition of TESARO in 

 (6). Therefore, under the agreement with AnaptysBio, GSK is responsible for the ongoing research, development, commercialization, and manufacturing of Jemperli as well as another monoclonal antibody, cobolimab (GSK4069889), a T-cell immunoglobulin and mucin domain-containing protein 3 antagonist.

Jemperli is a programmed cell death receptor-1-blocking antibody; it forms the backbone of GSK’s immuno-oncology-based R&D program, according to the company press release. The company is carrying out a robust clinical trial program for Jemperli, including studies of Jemperli alone and in combination with other therapies in gynecologic, colorectal, and lung cancers. In the United States, Jemperli is approved in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent, for treating adult patients with primary advanced or recurrent endometrial cancer that is dMMR, as determined by a FDA-approved test, or MSI-H. Separately, it is approved as a single agent to treat adult patients with dMMR-recurrent or advanced endometrial cancer, as determined by a FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and who are not candidates for curative surgery or radiation. Jemperli is also indicated in the US for treating patients with dMMR recurrent or advanced solid tumors, as determined by a FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.

Meanwile in the EU, Jemperli is indicated in combination with carboplatin-paclitaxel for treating adult patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy, and as monotherapy for treating adult patients with dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.

1. Faizan, U.; Muppidi, V. Uterine Cancer (Archived) [Updated Sep 4, 2023]. In 

; StatPearls Publishing, 2024.
2. Braun M. M.; Overbeek-Wager, E. A.; Grumbo, R. J. Diagnosis and Management of Endometrial Cancer. 

 (6), 468–474.
3. International Research on Cancer. Global Cancer Observatory. 

 gco.iarc.who.int/tomorrow/en (accessed July 1, 2024).
4. Concin, N.; Matias-Guiu, X.; Vergote, I.; et al. ESGO/ESTRO/ESP Guidelines for the Management of Patients with Endometrial Carcinoma. 

International Journal of Gynecologic Cancer

, 12–39.
5. AnaptysBio. Anaptysbio and Tesaro Announce Strategic Immuno-Oncology Antibody Collaboration. Press Release, March 13, 2024.
6. GSK. GSK Reaches Agreement to Acquire TESARO, an Oncology Focused Biopharmaceutical Company. Press Release, Dec. 3, 2018.

Articles

GSK’s application for using Jemperli (dostarlimab) plus chemotherapy for all adult patients with primary advanced or recurrent endometrial cancer has been accepted by the EMA.

GSK’s Application for Jemperli Plus Chemotherapy for Use in All Patients with Endometrial Cancer Accepted by EMA

AbbVie announced on June 27, 2024, that it has acquired Celsius Therapeutics (Celsius), a privately held biotechnology company specializing in anti-inflammatory disease therapies. AbbVie acquired Celsius in a $250 million cash deal. With it, AbbVie gains access to CEL383, Celsius' lead investigational drug candidate, a potential first-in-class anti-triggering receptor expressed on myeloid cells 1 (TREM1) antibody. CEL383 has completed a Phase I clinical study in the treatment of inflammatory bowel disease (IBD).

According to a company press release, TREM1 has been identified as a key disease driver gene in IBD. TREM1 is expressed on inflammatory monocytes and neutrophils, and—in these cell types as well as others—the gene is upstream of multiple known inflammatory pathways. It is known to act as an amplifier of inflammation (1).

"Given the potential relevance of TREM1 as a key driver of inflammation and pathology in IBD and other conditions, we are eager to advance the development of CEL383 with a goal of helping more patients with IBD achieve remission," said Kori Wallace, MD, PhD, vice-president, global head of immunology clinical development, AbbVie, in the press release.

CEL383 has demonstrated in preclinical assays that it inhibits TREM1 signaling and therefore reduces the levels of multiple inflammatory mediators that are of important clinical relevance in inflammatory conditions. The candidate has concluded a Phase I first-in-human, randomized, double-blind, placebo-controlled, single ascending dose study in which its safety, tolerability, and pharmacokinetics in healthy volunteers were evaluated.

"AbbVie shares our excitement about the potential of TREM1 inhibition for patients with inflammatory disease," said Tariq Kassum, MD, chief executive officer, Celsius. "I'd like to thank the Celsius team for their relentless efforts in the discovery of CEL383. We look forward to the further development of this promising program, which we hope will offer a new approach to the treatment of IBD."

This acquisition follows moves that AbbVie made earlier this year to strengthen its inflammatory and autoimmune disease therapeutics portfolio. In February 2024, the company entered into a 

 with clinical-stage immunotherapy company OSE Immunotherapeutics. Under this partnership, AbbVie and OSE Immunotherapeutics will develop OSE-230, a preclinical-stage monoclonal antibody (mAb), to treat chronic and severe inflammation (2).

, a clinical-stage biopharmaceutical company focusing on autoimmune diseases. With this acquisition, AbbVie gains a lead asset, NX-13, an oral nucleotide oligomerization domain-like receptor family member X1 (NLRX1) agonist with a bimodal mechanism of action. NLRX1 is known to regulate immunometabolism and inflammation; its activation impacts multiple mechanisms of IBD pathogenesis, according to AbbVie in a press release (3). Landos’ NX-13, which is in Phase II clinical development, is an anti-inflammatory agent that facilitates epithelial repair.

1. Zhang, C.; Kan, X.; Zhang, B.; Ni, H.; Shao J. The Role of Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) in Central Nervous System Diseases. 

, 84. DOI: 10.1186/s13041-022-00969-w
2. AbbVie. AbbVie and OSE Immunotherapeutics Announce Partnership to Develop a Novel Monoclonal Antibody for the Treatment of Chronic Inflammation. Press Release, Feb. 28, 2024.
3. AbbVie. AbbVie to Acquire Landos Biopharma, Further Strengthening its Portfolio in Inflammatory and Autoimmune Diseases. Press Release, March 25, 2024.

This acquisition will give AbbVie acces to Celsius Therapeutics' lead drug candidate, CEL383, a potential first-in-class anti-TREM1 antibody for treating IBD.

AbbVie Advances Inflammatory Disease Portfolio with Celsius Therapeutics Acquisition

Johnson & Johnson has gained two new bispecific antibody assests with the completion of its $850 million acquisition of Proteologix, a privately held biotechnology company focused on bispecific antibodies for immune-mediated diseases. The acquisition includes PX-128 and PX-130, bispecific antibodies in early phase development for immune-mediated disease, the company announced on June 21, 2024. The transaction includes a potential additional milestone payment to Proteologix. Johnson & Johnson initially announced the acquisition in May 2024 (1).

In addition to PX-128 and PX-130, the acquisition boosts Johnson & Johnson’s bispecifics portfolio with eight other bispecific antibody programs. These programs are applicable across a variety of other diseases. PX-128 targets interleukin-13 (IL-13) plus thymic stromal lymphopoietin (TSLP) and is ready to enter Phase I development for moderate-to-severe atopic dermatitis (AD) and moderate-to-severe asthma. PX-130 targets IL-13 plus IL-22 and is in preclinical development for moderate-to-severe AD. IL-13 is responsible for T helper 2 cell skin inflammation, and TSLP is responsible for tissue inflammation; both are disease-driveway pathways for AD and asthma (1). Meanwhile, although IL‐22 plays an important role in wound healing and skin protection against infections, it can also contribute to the onset of several inflammatory skin diseases, including AD, psoriasis, and allergic contact dermatitis (2).

“We look forward to continuing the development of PX-128 and PX-130 alongside the Proteologix team as they join Johnson & Johnson,” said David Lee, Global Immunology Therapeutic Area head, Johnson & Johnson Innovative Medicine, in the press release. “These two bispecific antibodies have the potential to become best-in-disease therapeutics for people living with moderate-to-severe [AD] and asthma by targeting multiple disease-driving pathways. We are thrilled to start integrating them into our … Immunology portfolio.”

Johnson & Johnson has been aggressively growing its immunology portfolio with acquisitions of bispecific antibody assets. In May 2024, the company 

 its intention to acquire a wholly owned subsidiary of Numab Therapeutics, a clinical-stage biotechnology company specializing in immunology and oncology therapeutics, for approximately $1.25 billion in an all-cash transaction, which is expected to close in the second half of this year (3). This acquisition would give Johnson & Johnson the global rights to NM26, an investigational bispecific antibody soon to enter Phase II studies for AD, adding to the bispecifics assets it has acquired in the Proteologix acquisition.

“The Proteologix team has developed a promising early pipeline of bispecific antibodies that are a strong complement and strategic fit for our innovation strategy,” said Candice Long, worldwide vice-president, Immunology, Johnson & Johnson, in the press release. “This acquisition is yet another example of our ongoing commitment to redefine the standard of care for immune mediated diseases.”

Meanwhile Johnson & Johnson’s own bispecific antibodies received regulatory approvals. In August 2022, the European Commission (EC) approved TECVAYLI (teclistamab), and in August 2023, FDA approved TALVEY (talquetamab-tgvs) (4,5). Both bispecific antibodies were respectively approved for treating relapsed or refractory multiple myeloma. In Europe, the EC also approved a reduced dosing frequency in August 2023 for teclistamab in patients who have achieved a complete response or better for a minimum of six months (4).

1. Johnson & Johnson. Johnson & Johnson to Acquire Proteologix, Inc. to Lead in Atopic Dermatitis Treatment. Press Release, May 16, 2024.
2. Lopez D. V.; Kongsbak-Wismann, M. Role of IL-22 in Homeostasis and Diseases of the Skin. 

 (6), 314–322. DOI: 10.1111/apm.13221
3. Johnson & Johnson. Johnson & Johnson to Obtain Rights to a Clinical-Stage Bispecific Antibody to Address Distinct Patient Needs in Atopic Dermatitis. Press Release, May 28, 2024.
4. Johnson & Johnson. European Commission Approves Reduced Dosing Frequency for Janssen’s Bispecific Antibody TECVAYLI (teclistamab). Press Release, Aug. 18, 2023.
5. Johnson & Johnson. U.S. FDA Approves TALVEY (talquetamab-tgvs), a First-in-Class Bispecific Therapy for the Treatment of Patients with Heavily Pretreated Multiple Myeloma. Press Release, Aug. 10, 2023.

Johnson & Johnson gets two bispecific antibodies in early phase development for immune-mediated diseases through its Proteologix acquisition. 

Johnson & Johnson Completes Proteologix Acquisition, Gains Bispecific Antibody Assets

Novo Nordisk will invest $4.1 billion (approximately DKK27 billion) to build a second fill/finish manufacturing facility in Clayton, N.C., which wiil strengthen the company’s ability to produce current and future injectable therapeutics for treating obesity and other serious chronic diseases. The new investment boosts the company's current 2024 investments in production to $6.8 billion, an increase from the previous year's investment of $3.9 billion (not including acquisitions), according to a June 24, 2024 company press release.

The $4.1 billion investment marks one of the largest manufacturing investments in the company’s history, according to the release. The expansion will add 1.4 million square feet of production space for aseptic manufacturing and finished production processes, which will double the combined square footage of the company’s three existing facilities in North Carolina. One thousand new jobs will be added to the nearly 2500-person workforce in that region. Construction of the new facility will be gradually finalized between 2027 and 2029.

“It took us a century to reach 40 million patients, but through this expansion and continued investment in our global production, we’re building Novo Nordisk’s ability to serve millions more people living with serious chronic diseases in the future,” said Lars Fruergaard Jørgensen, president and CEO of Novo Nordisk, in the press release. “This is yet another real signal of our efforts to scale up our production to meet the growing global need for our life-changing medicines and the patients of tomorrow.”

The facility will feature sustainable components, such as roof-top solar panels and innovative water strategies. The company’s goal is to obtain Leadership in Energy and Environmental Design Gold certification, which is recognized as a standard of excellence in the construction of healthy, efficient, and carbon- and cost-saving green buildings, according to the press release.

“Clayton was the first manufacturing site for Novo Nordisk in the [United States], and this new, large-scale investment confirms the continued importance of our production facilities there as cornerstones of our company’s growth,” said Henrik Wulff, executive vice-president, Product Supply, Quality & IT, Novo Nordisk, in the release. “For decades, we have partnered to foster a well-trained, dedicated, and diverse local workforce in North Carolina. In Clayton and across our global manufacturing sites, we are driven by one purpose: to deliver more for the millions of people living with chronic diseases—and this facility will help us achieve just that.”

In addition to its expansion activities in the US, the company also has expansion in Europe underway. In November 2023, it announced a 

 to its existing production site in Chartres, France, where it plans to significantly increase capacity by adding aseptic production and finished production processes, as well as an extension of the site’s current laboratory for quality control (1). The investment includes capacity expansion for the company’s glucagon-like peptide-1 products. Construction at the Chartres site will gradually be finalized between 2026 and 2028.

1. Novo Nordisk. Novo Nordisk Invests More Than 16 Billion Danish Kroner in Expansion of Production Facilities in Chartres, France. Press Release, Nov. 23, 2023.

This $4.1 billion investment to build a second fill/finish manufacturing facility in Clayton, N.C., boosts Novo Nordisk's current 2024 investments in production to $6.8 billion.

Novo Nordisk Aims to Invest $4.1 Billion to Expand Manufacturing Capacity in US

Sarepta Therapeutics has received expanded approval from FDA for Elevidys (delandistrogene moxeparvovec-rokl), its gene therapy for treating Duchenne muscular dystrophy (DMD). The expanded approval now includes treatment of non-ambulatory individuals four years of age and older with DMD with a confirmed mutation in the DMD gene.

 in June 2023 (1) under accelerated approval for ambulatory individuals four through five years of age with DMD with a confirmed mutation in the DMD gene. The accelerated approval was converted to traditional approval for ambulatory patients aged four and up. Additionally, FDA granted accelerated approval to non-ambulatory patients aged four and up.

The efficacy of Elevidys was evaluated in two double-blind, placebo-controlled studies and two open-label studies. The expanded approval was based on the evaluation of data that showed compelling secondary endpoints and exploratory endpoints, which indicated clinical benefit compared to placebo, despite Elevidys failing to meet its statistical primary endpoint of improvement versus placebo. FDA’s decision took into account the totality of evidence, including the potential risks associated with the product, the life-threatening and debilitating nature of the disease, and the urgent unmet medical need, according to a June 20, 2024 press release.

“Today’s approval broadens the spectrum of patients with Duchenne muscular dystrophy eligible for this therapy, helping to address the ongoing, urgent treatment need for patients with this devastating and life-threatening disease,” said Peter Marks, MD, PhD., director of FDA’s Center for Biologics Evaluation and Research, in the press release. “We remain steadfast in our commitment to help advance safe and effective treatments for patients who desperately need them.”

Elevidys, a recombinant gene therapy, is the first gene therapy to be approved for treating this specific population of DMD patients, according to FDA (1). It is designed to deliver a gene that enables production of Elevidys micro-dystrophin, a shortened protein containing selected domains of the dystrophin protein present in normal muscle cells. Elevidys is administered as a single intravenous dose.

DMD is a rare and serious genetic condition that worsens over time. It leads to weakness and wasting away of muscles. The disease is caused by a defective gene that leads to abnormalities in, or absence of, the dystrophin protein, which helps keep muscle cells intact, according to the press release. Symptoms of DMD may include trouble walking and running, falling frequently, fatigue, and learning disabilities/difficulties. Patients may also experience heart issues and breathing problems. Muscle weakness associated with DMD typically begins in childhood between the ages of three and six. The condition mainly affects males, although females can be affected in rare cases. FDA estimates that approximately one in every 3300 boys are affected by DMD.

1. FDA, FDA Approves First Gene Therapy for Treatment of Certain Patients with Duchenne Muscular Dystrophy. Press Release, June 22, 2023.

Sarepta Therapeutics received expanded approval from FDA for Elevidys in the treatment of DMD in non-ambulatory patients as ell as ambulatory patients.

Sarepta’s Elevidys for Duchenne Muscular Dystrophy Gets Expanded FDA Approval

FDA has approved Netherlands-based immunology company argenx's VYVGART Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) for treating adult patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This is the third indication for the biologic approved by FDA, making it the first and only neonatal Fc receptor (FcRn) blocker that has been approved for treating CIDP, the company announced on June 21, 2024. The approval is for a once weekly 30-to-90 second subcutaneous injection.

FDA’s approval is based on a clinical study (ADHERE) in which it was demonstrated that 69% of patients treated with VYVGART Hytrulo showed evidence of clinical improvement, regardless of whether or not they had had prior treatment. Improvements in mobility, function, and strength were demonstrated. The clinical trial, which the company stated is the largest clinical trial to date studying CIDP, met its primary endpoint in demonstrating a 61% reduction in the risk of relapse versus placebo.

“argenx continues to pursue our ambition to turn science into solutions for patients with severe autoimmunity,” said Luc Truyen, MD, PhD, chief medical officer, argenx, in the press release. “Patients have been waiting, and today argenx is delivering the first innovative treatment for CIDP in more than 30 years. VYVGART Hytrulo is a precision tool that has been shown to drive meaningful benefits for patients. Today’s FDA approval means that CIDP patients have a transformational new treatment option and further affirms the therapeutic profile of VYVGART Hytrulo and the potential of FcRn blockade in IgG [immunoglobulin G]-mediated autoimmune diseases.”

CIDP is a progressive immune-mediated neuromuscular disorder of the peripheral nervous system (1). It is a rare and debilitating condition in which patients experience a range of disabling mobility and sensory issues, including trouble standing from a seated position, pain and fatigue, and frequent tripping or falling. Currently, 85% of patients with CIDP require ongoing treatment, and nearly 88% of treated patients continue to experience residual impairment and disability.

“While CIDP patients face many daily concerns and challenges, fear of disease progression should not be one of them. CIDP can be debilitating and have significant impact on quality of life, and many patients with CIDP require treatments that may be burdensome. The approval of this promising new treatment option for CIDP may provide hope to patients that they can treat their disease beyond just managing symptoms. CIDP patients deserve treatment options, and we look forward to a future of choices for optimal and individualized care,” said Lisa Butler, executive director, GBS|CIDP Foundation, in the press release.

“Today marks a groundbreaking day for the treatment of CIDP. Existing treatments have been limited to corticosteroids and plasma-derived therapies. These treatments, while effective for many patients, can be challenging for some patients to receive,” Jeffrey Allen, MD, professor, Department of Neurology, University of Minnesota, and principal investigator in the ADHERE trial, added. “Today’s approval of VYVGART Hytrulo gives doctors and patients a new, safe, and effective treatment option that may lessen the burden of treatment that some patients experience.”

VYVGART Hytrulo is also approved in the United States for treating generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor antibody positive.

For access to the treatment, argenx has established a patient support program, called My VYVGART Path, to help patients and health care providers navigate access. The program resources include disease and product education, access support and benefits verification, and financial assistance programs for eligible patients.

1. Gogia, B.; Rocha Cabrero, F.; Khan Suheb, M. Z.; et al. Chronic Inflammatory Demyelinating Polyradiculoneuropathy. (Updated March 4, 2024). In 

FDA has approved argenx's VYVGART Hytrulo for a new indication, treating chronic inflammatory demyelinating polyneuropathy.