c-Fos

Currently, only three CXCR4 (C-X-C motif chemokine receptor 4) antagonists have been approved globally: Plerixafor, Motixafortide, and Mavorixafor, indicating significant market potential. With a deeper understanding of the role of CXCR4 in tumor progression, the demand for CXCR4 antagonists continues to grow. In 2024, the global CXCR4 antagonist market is valued at several billion RMB, with steady growth projected in the coming years. Key players in the global market include Sanofi, BioLineRx, X4 Pharmaceuticals, Eli Lilly, and Roche. The increasing global aging population and the rising incidence of chronic diseases such as cancer create a vast market opportunity for anti-tumor drugs like CXCR4 antagonists. Advances in drug development further inject vitality into the CXCR4 antagonist market. Global Transactions of CXCR4 Antagonists in Patsnap SynapseMechanism of Action of CXCR4 AntagonistsSchematic diagram of CXCR4[1]CXCR4 is a seven-transmembrane G-protein-coupled receptor (GPCR) widely expressed across various cell types, particularly immune cells, hematopoietic stem cells, endothelial cells, and numerous tumor cells. Its primary ligand is the chemokine CXCL12 (also known as SDF-1, stromal cell-derived factor 1). Binding of CXCL12 to CXCR4 induces conformational changes in CXCR4, activating the G-protein complex. The G-protein complex dissociates into Gα and Gβγ subunits, with Gβγ activating the PI3K and RAS-MAPK pathways. CXCL12-CXCR4/CXCR7 signaling pathway[2]Subsequently, the Gβγ subunit activates guanine nucleotide exchange factors (GEFs), such as SOS. These GEFs facilitate the exchange of GDP for GTP on RAS proteins, activating them. Activated RAS proteins, in turn, stimulate the MAPK (mitogen-activated protein kinase) and MEK1/2 (mitogen-activated protein kinase kinase 1/2) pathways. Activated MEK1/2 phosphorylates and activates ERK1/2 (extracellular signal-regulated kinases 1/2). ERK1/2 activation promotes cell proliferation and survival. Additionally, ERK1/2 can activate transcription factors such as c-Fos and c-Jun, further regulating gene expression. Once activated, ERK1/2 enters the nucleus and phosphorylates various transcription factors, including c-Fos and c-Jun, which bind to specific DNA sequences to regulate gene expression, ultimately affecting cell proliferation, differentiation, and survival. When CXCR4 interacts with CXCL12, it activates signaling pathways including RAS-MAPK, PI3K-AKT-mTOR, JAK-STAT, and PLC. These pathways play crucial roles in cell migration, proliferation, and survival. Under normal physiological conditions, CXCR4 is critical for regulating cell migration and localization during development, homeostasis, and inflammation, aiding immune system activation and facilitating cell movement. High CXCR4 expression is associated with poor prognosis and chemotherapy resistance in various cancer subtypes, partly due to enhanced interactions between cancer cells and the stroma. The CXCR4/CXCL12 signaling axis plays a central role in tumor progression through autocrine and paracrine mechanisms. Similar to other GPCRs, CXCR4 undergoes homo- or heterodimerization in its functional signaling regions on the cell surface. Receptor aggregation in dimers or oligomers significantly enhances the sensitivity and intensity of chemokine responses. Schematic representation of the signaling pathways activated by CXCR4[3]CXCR4 antagonists block the binding of CXCL12 to CXCR4, inhibiting tumor cell migration and invasion, reducing HIV infection and transmission, regulating immune cell migration, and promoting hematopoietic stem cell mobilization, showcasing significant applications across multiple fields. In oncology, CXCR4 antagonists like Motixafortide, combined with Keytruda and chemotherapy, have significantly improved objective response rates (ORR) and progression-free survival (PFS) in patients with advanced pancreatic ductal adenocarcinoma and demonstrated antitumor effects in breast and lung cancers. For HIV treatment, CXCR4 antagonists like Plerixafor and AMD3100 reduce viral infection and spread by blocking HIV-CXCR4 interactions while enhancing the host immune response. In autoimmune diseases, CXCR4 antagonists mitigate inflammatory responses by reducing immune cell migration, alleviating symptoms in conditions like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In hematopoietic stem cell mobilization, CXCR4 antagonists such as Plerixafor and Motixafortide facilitate the release of hematopoietic stem cells from bone marrow into peripheral blood for autologous transplantation in diseases like non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). Market Drivers for CXCR4 Antagonist DevelopmentWith advancements in precision medicine, targeted therapeutics are increasingly prioritized. As a critical target in various diseases, CXCR4 antagonist development aligns with the precision medicine trend. CXCR4 antagonists hold significant value in treating hematological disorders such as multiple myeloma. Furthermore, these antagonists are being explored for new indications like breast cancer, WHIM syndrome, and Waldenström’s macroglobulinemia, all of which represent substantial patient populations and offer vast market potential. The combination of CXCR4 antagonists with other therapies, such as chemotherapeutics and immune checkpoint inhibitors, markedly enhances therapeutic efficacy and addresses clinical needs. Additionally, governmental and regional policy and financial support for innovative drug development have attracted extensive attention to and support for CXCR4 antagonists as promising innovative drugs. Top 10 Indications of CXCR4 Antagonists in Patsnap SynapseTechnological advancements and innovation have significantly driven the development of CXCR4 antagonists. Novel small-molecule antagonists such as Plerixafor and Mavorixafor, as well as peptide-based antagonists like Motixafortide, have demonstrated high affinity and favorable pharmacological efficacy. The application of antibody-based therapies and nanotechnology has further enhanced drug specificity and effectiveness. Multiple clinical trials have highlighted the substantial efficacy and safety of CXCR4 antagonists across various diseases. Some of these drugs have received FDA designations as Breakthrough Therapies or Fast Track therapies, expediting their development and approval. Targets of CXCR4 Antagonists in Patsnap SynapseRegional Development Analysis of CXCR4 AntagonistsNorth America leads in the development and market adoption of CXCR4 antagonists due to its advanced medical technology and robust regulatory framework. Significant investments from both the U.S. government and private sector have spurred research by major pharmaceutical companies and biotech startups. With a substantial patient population suffering from cancers, HIV infections, immune disorders, and requiring hematopoietic stem cell transplants, demand for CXCR4 antagonists remains strong. Key drugs, including Plerixafor and Mavorixafor, have achieved notable progress in this region. Regional Distribution of CXCR4 Antagonist Research and Development in Patsnap SynapseIn Europe, biopharmaceutical R&D is highly active, with many institutions and companies advancing work on CXCR4 antagonists. While the European Medicines Agency (EMA) maintains stringent drug approval processes, it is continuously optimizing these procedures to accelerate the market entry of innovative medicines. Europe's comprehensive healthcare systems and high patient receptivity to novel therapies drive demand for CXCR4 antagonists in oncology, HIV, immune disorders, and stem cell transplantation. Prominent drugs such as Motixafortide and Balixafortide are undergoing extensive clinical trials in the region. In Asia, particularly in countries like China, Japan, and South Korea, the biopharmaceutical market is expanding rapidly, with increasing demand for innovative drugs. Rich clinical trial resources and a large patient base create favorable conditions for CXCR4 antagonist research. The region exhibits significant potential due to its high prevalence of cancers, HIV infections, immune disorders, and stem cell transplant requirements. Representative drugs, such as Balixafortide, introduced by Fosun Pharma, are undergoing clinical trials for breast cancer. Numerous Asian pharmaceutical companies and research institutions are actively developing various CXCR4 antagonists. Market Competition Landscape for CXCR4 AntagonistsDevelopment Stage Distribution of CXCR4 Antagonists in Patsnap SynapsePlerixafor was the first FDA-approved CXCR4 antagonist, primarily used in autologous hematopoietic stem cell transplantation. Sanofi holds a first-mover advantage in the CXCR4 antagonist market, with a significant market share. The successful application of Plerixafor in stem cell transplantation has provided Sanofi with valuable data and experience, enabling further exploration of additional indications. For instance, Sanofi is investigating the potential of Plerixafor in oncology, particularly in enhancing immune cell infiltration within the tumor microenvironment and improving the efficacy of immunotherapies. Moreover, Sanofi is exploring Plerixafor's application in HIV treatment, aiming to reduce viral infection and transmission by blocking the interaction between HIV and CXCR4. Major Research Institutions for CXCR4 Antagonists in Patsnap SynapseThe CXCR4 antagonist Mavorixafor, the flagship product of X4 Pharmaceuticals, has received FDA priority review designation for the treatment of WHIM syndrome. WHIM syndrome is a rare primary immunodeficiency characterized by recurrent infections, hypogammaglobulinemia, and bone marrow abnormalities. The approval of Mavorixafor represents the first targeted therapy for WHIM syndrome, addressing an unmet medical need. In Phase 3 clinical trials for WHIM syndrome, Mavorixafor demonstrated positive outcomes, including favorable safety and efficacy profiles. These clinical results not only supported its regulatory submission but also bolstered X4 Pharmaceuticals’ market presence and investor confidence. Additionally, X4 Pharmaceuticals is actively exploring the use of Mavorixafor in other conditions, such as HIV infection and certain forms of chronic neutropenia. CXCR4 Antagonist Portfolio of X4 Pharmaceuticals in Patsnap SynapseBioLineRx's Motixafortide has shown remarkable efficacy in the treatment of pancreatic cancer and other malignancies. In collaboration with major pharmaceutical companies such as Merck and Roche, BioLineRx is advancing the development and commercialization of Motixafortide. Clinical trial data indicate that the combination of Motixafortide with Keytruda and chemotherapy significantly improves objective response rates (ORR) and progression-free survival (PFS) in patients. Motixafortide has also demonstrated promising results in autologous hematopoietic stem cell transplantation (ASCT). When combined with granulocyte colony-stimulating factor (G-CSF), Motixafortide substantially enhances the efficiency and quality of CD34+ stem cell collection. In the GENESIS global Phase 3 trial, the combination achieved significantly higher success rates compared to the placebo group, with 88.8% of patients achieving an optimal CD34+ cell dose in a single apheresis session and 92.5% in up to two sessions. Beyond pancreatic cancer and ASCT, BioLineRx is investigating Motixafortide in other oncology applications, including breast cancer, gastric cancer, and prostate cancer. Preliminary findings suggest that Motixafortide enhances antitumor immune responses by blocking CXCR4 receptors, reducing immunosuppressive cells in the tumor microenvironment, and increasing the infiltration of effector T cells and other antitumor immune cells. BioLineRx is also exploring combination therapies involving Motixafortide and other immunotherapies, such as PD-1 inhibitors and chemotherapeutic agents, which have demonstrated synergistic effects in early studies. CXCR4 Antagonist Portfolio of BioLineRx in Patsnap SynapseBioLineRx has established strategic partnerships with major pharmaceutical companies such as Merck and Roche to jointly develop and promote Motixafortide. These collaborations have accelerated the clinical research and market entry of Motixafortide, enhancing its global market presence. For example, BioLineRx partnered with Merck to conduct clinical trials of Motixafortide in combination with Keytruda for the treatment of pancreatic cancer. Additionally, BioLineRx collaborated with China-based Genfleet Therapeutics to develop Motixafortide for the Chinese market. Genfleet is independently responsible for designing and developing first-line combination therapies targeting advanced pancreatic ductal adenocarcinoma in mainland China. This partnership expedites Motixafortide's entry into the Chinese market, addressing the treatment needs of local patients. Fosun Pharma, through its collaboration with Polyphor, introduced Balixafortide for the treatment of breast cancer and other potential cancers. Balixafortide has demonstrated notable efficacy in breast cancer treatment. Clinical trial data from Fosun Pharma showed that Balixafortide, combined with eribulin mesylate injection, exhibited good efficacy and safety in HER2-negative metastatic breast cancer patients. In a global Phase 3 clinical trial, this combination achieved an objective response rate (ORR) of 40%, a median progression-free survival (mPFS) of 8.5 months, and a disease control rate (DCR) of 75%. Fosun Pharma is also exploring the application of Balixafortide in other cancers, such as pancreatic ductal adenocarcinoma (PDAC). According to an announcement by Spexis AG, Balixafortide demonstrated good safety and efficacy in PDAC patients, inhibiting tumor growth and metastasis. Additionally, Fosun Pharma is investigating combination therapies involving Balixafortide and other chemotherapeutic agents. For instance, the combination of Balixafortide with eribulin not only enhanced therapeutic efficacy but also reduced side effects, improving patients' quality of life. This combined therapy strategy offers new approaches to cancer treatment. ConclusionCXCR4 antagonists demonstrate immense potential across various medical fields, particularly in oncology, HIV infection, immune disorders, and hematopoietic stem cell transplantation. Advances in technology and supportive policies have provided robust backing for the development of CXCR4 antagonists, which hold promising market prospects. As more clinical trials are conducted and new drugs are approved, CXCR4 antagonists are poised to become vital tools for treating diverse diseases, offering hope and new options for patients. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery! Refrence  1.Yu, J., X. Zhou, and L. Shen, CXCR4-Targeted Radiopharmaceuticals for the Imaging and Therapy of Malignant Tumors. Molecules, 2023. 28(12).2.Yang, Y., et al., CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications. Int J Biol Sci, 2023. 19(11): p. 3341-3359.3.Bianchi, M.E. and R. Mezzapelle, The Chemokine Receptor CXCR4 in Cell Proliferation and Tissue Regeneration. Front Immunol, 2020. 11: p. 2109.

As a malignant disease of the liver cells, hepatocellular carcinoma (HCC) is one of the main causes of cancer-related deaths. While the treatment options for this aggressive type of cancer remain limited, the incidence is increasing. A research team has now described a molecular signalling pathway that plays a key role in the development of liver cancer, thereby identifying a potential new starting point for the development of therapeutic treatments. As a malignant disease of the liver cells, hepatocellular carcinoma (HCC) is one of the main causes of cancer-related deaths. While the treatment options for this aggressive type of cancer remain limited, the incidence is increasing. A research team led by Latifa Bakiri and Erwin Wagner from MedUni Vienna’s Clinical Institute for Laboratory Medicine has now described a molecular signalling pathway that plays a key role in the development of liver cancer, thereby identifying a potential new starting point for the development of therapeutic treatments. The results of the study have just been published in the journal Proceedings of the National Academy of Sciences (PNAS). In their research, the international team led by MedUni Vienna, built on earlier study results that had suggested the involvement of certain transcription factors (c-Fos and c-Jun) in the development of hepatocellular carcinomas. Transcription factors are proteins involved in numerous cellular processes, including the control of genes associated with the development of HCC. To advance these findings, the scientists developed a new mouse model. The experiments carried out with these proteins showed that the combination with previously unexplored (Fra) proteins in this context triggers the cascade of tumour formation. Specifically, this involves the interaction between c-Jun and Fra-2, which the studies showed to be essential in the development of liver cancer. "It is remarkable that we were able to reverse tumour growth by switching off the protein combination of c-Jun and Fra-2," reports the head of the study Erwin Wagner. The study also showed that tumour growth can be stopped by blocking a specific gene (c-Myc). "Accordingly, our research results suggest that the molecular signalling pathway we have identified represents a promising starting point for further research into HCC and the development of new therapeutic measures," concludes first author Latifa Bakiri. Hepatocellular carcinoma is an aggressive tumour with rapid progression and limited therapeutic options. Even though the incidence has increased significantly in Western countries in recent decades, this type of cancer is still comparatively rare. However, due to its poor prognosis, HCC is one of the most common causes of cancer-related deaths. HCC occurs in particular in the context of advanced liver disease (cirrhosis, chronic hepatitis B) and is often only diagnosed at a late stage.

On March 14th, British pharmaceutical giant AstraZeneca announced its intention to acquire Amolyt Pharma, a clinical-stage biotech company focused on the development of innovative therapies for rare endocrine diseases. The acquisition is set to further strengthen AstraZeneca's rare disease business unit, Alexion, by bolstering its late-stage product development pipeline and adding a critical component to its bone metabolism portfolio - eneboparatide (AZP-3601), a therapeutic peptide currently in phase III clinical trials. This drug has a novel mechanism of action aimed at addressing key therapeutic goals for patients with hypoparathyroidism. It is reported that patients with hypoparathyroidism, due to insufficient production of parathyroid hormone (PTH), suffer from severe calcium and phosphate metabolism dysregulation, leading to symptoms and complications that can alter quality of life, including chronic kidney disease among others. There are an estimated 115,000 patients in the United States and about 107,000 in the European Union affected by this condition, with approximately 80% being female. Parathyroid hormone is secreted by the four tiny parathyroid glands located near the thyroid gland. When there is an insufficiency or absence of PTH secretion, it leads to a decrease in the concentration of calcium ions in the blood and an increase in phosphate levels, which is the most significant laboratory finding for the diagnosis of hypocalcemia. The most common cause of the loss of PTH is injury or removal of the parathyroid glands during thyroid or neck surgery. This condition disrupts the normal balance of calcium and phosphate metabolism in the body, causing a range of symptoms and complications including, but not limited to, muscle cramps, twitching, tremors, fatigue, emotional instability, and potentially, if left untreated, osteomalacia, increased risk of fractures, and dental issues. Therefore, finding therapies that can substitute the function of PTH is crucial for patients with hypocalcemia, with the goal of restoring calcium-phosphate homeostasis and improving patient quality of life. As a PTH receptor 1 (PTH1R) agonist, eneboparatide employs a novel mechanism of action specifically designed for the therapeutic aim of treating hypoparathyroidism. This peptide is capable of highly affinity binding to the R0 conformation of PTH1R receptors. Despite its short pharmacokinetic half-life, eneboparatide is still able to induce a sustained elevation in serum calcium levels in vivo. Such a design allows eneboparatide to vigorously promote calcium reabsorption in the renal tubules and exert physiologically significant effects on bone turnover, which has been confirmed by animal experiments and human studies. In the year 2016, a research team from Harvard Medical School developed two murine models of acquired hypoparathyroidism and utilized these models to evaluate the efficacy of PTH(1-34) and a long-acting PTH analog (LA-PTH) in regulating blood calcium levels. The results show that a single subcutaneous injection of LA-PTH can more effectively increase serum calcium levels compared to PTH(1-34) administered at a dose tenfold higher, with the effect lasting over 24 hours, and without leading to excessive urinary calcium excretion. In a phase I clinical trial conducted on healthy volunteers, eneboparatide demonstrated the ability to rapidly induce a steady increase in serum calcium levels along with the dosage increment, and this elevation was maintained throughout the entire treatment period. More importantly, there was no observed increase in urinary calcium excretion during the study, nor were there any changes in bone biomarkers. This indicates that eneboparatide can raise serum calcium levels without causing negative effects on urinary calcium excretion or bone metabolism, showing good safety and potential efficacy. Phase II clinical data have shown that enboparatide successfully restores serum calcium levels to normal and holds promise for eliminating the patient's dependency on daily calcium and vitamin D supplements. In adults with chronic hypophosphatemia and hypercalciuria, the results indicate that enboparatide can normalize calcium content in the urine. Moreover, for patients with hypophosphatemia, enboparatide also helps maintain bone mineral density, which is a significant potential benefit for patients at increased risk of osteoporosis or reduced bone density. About PTH1R Currently, the main clinical targets for the treatment of hypoparathyroidism are the PTH1R (developing safer and more effective synthetic PTH analogues or oral small-molecule PTH1R agonists) and the vitamin D receptor (a type of nuclear receptor, with vitamin D receptor agonists able to control calcium and bone metabolism, and regulate growth and differentiation of various cell types). Parathyroid hormone 1 receptor 1 (PTH1R) belongs to the Class B G protein-coupled receptor family. This receptor can be activated by two different endogenous peptide agonists, namely parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP), leading to the activation of Gs, Gq, and β-arrestin, thereby modulating various signaling pathways and exerting different biological effects. Research has shown that PTH can regulate the calcium and phosphate balance in bones and kidneys, while PTHrP regulates the cellular proliferation and differentiation in developing bones and other tissues. Natural PTH and modified agonist peptides can induce significant anabolic bone formation and have been used in clinical treatments for osteoporosis. Therefore, PTH1R is also considered a key target for the treatment of hypoparathyroidism and osteoporosis, and can be treated through the injection of PTH or PTHrP analogues. According to statistics from the Synapse database, there are currently a total of 87 therapeutic drug development projects worldwide targeting PTH1R. The types of drugs primarily consist of recombinant peptides, biosimilars, hormones, etc., with only a small portion being small-molecule drugs. The natural ligands for Class B GPCRs are peptide hormones, which activate the receptors by binding to a larger open pocket within the transmembrane domain. Additionally, the extracellular domain is required for high-affinity ligand-receptor interactions. Therefore, drug development targeting Class B GPCRs primarily involves biologics or recombinant peptides, which is significantly different from the current market trend where drugs targeting Class A family GPCR members are mainly small molecules. Class B GPCRs belong to the peptide hormone receptor family and are common drug targets for various metabolic disorders, including osteoporosis, Type 2 diabetes, obesity, cardiovascular diseases, and migraines. Developing oral medications targeting Class B GPCRs, to improve patient quality of life, minimize side effects, and reduce costs still poses certain challenges. Other Drugs for the Treatment of Hypoparathyroidism Currently, other candidate drugs targeting PTH1R for the clinical treatment of hypoparathyroidism include the PTH1R agonist PCO-371, which is developed by Chugai Pharmaceutical and is in Phase 1 clinical studies. In 2016, Chugai Pharmaceutical published an article in the journal Nature Communications, detailing the development of an orally active small molecule PTHR1 agonist, PCO-371, for the treatment of hypoparathyroidism. PCO-371 is a novel orally active small molecule that functions as a full agonist of PTHR1. Oral administration of PCO-371 in osteoporotic rats significantly increased bone turnover rate, although the increase in bone mass was limited. In rats with hypocalcemia, PCO-371 restored serum calcium levels without increasing urinary calcium, and its effect was stronger and more sustainable than that of injected PTH. These results suggest that PCO-371 may offer a new therapeutic option for PTH-related disorders, including hypoparathyroidism. PCO371 was obtained through cellular-level functional screening. It can stimulate COS-7 cells expressing PTH1R to produce cAMP as well as enhance the activity of phospholipase C. The action of PCO371 on PTH1R is primarily through interaction with the transmembrane region and is not affected by the receptor's extracellular domain. DOI: 10.1038/ncomms13384 PCO371 not only can dose-dependently increase the expression of bone-related messenger RNAs such as Fos, osteocalcin, and receptor activator of nuclear factor-κB ligand (RANKL), but it can also dose-dependently reduce the mRNA expression of osteoprotegerin and sclerostin. DOI: 10.1038/ncomms13384 Additionally, PCO371 is capable of inducing bone resorption activity similar to that of PTH in fetal rat long bone organ cultures. Using concentrations of 1 μmol l^-1 or higher, PCO371 stimulated the release of isotopically labeled ^45Ca from pre-labeled bone as effectively as hPTH(1-34). Moreover, the authors investigated the effects of combined treatment with PCO371 and alfacalcidol in a hypocalcemic rat model following parathyroidectomy. Administration of 75 ng kg^-1 of alfacalcidol alone normalized serum calcium to within or above the target therapeutic range but was accompanied by substantial urinary calcium excretion. A daily oral dose of 6 mg/kg^-1 of PCO371 with 38 ng kg^-1 of alfacalcidol raised serum Ca to levels comparable to those achieved with 75 ng kg^-1 of alfacalcidol alone. The combination of PCO371 and alfacalcidol allowed for a reduction in the dose of alfacalcidol, thereby decreasing urinary calcium excretion. This suggests that PCO371 can be used in the treatment of hypoparathyroidism, either as a monotherapy or as an adjunct to conventional therapy. DOI: 10.1038/ncomms13384 In 2020, the Chugai team continued to publish articles in the "Journal of Medicinal Chemistry," where they discussed the small molecule hPTHR1 agonist PCO371 and its lead compound 1 (CH5447240), which could induce hypocalcemic and bile acid synthesis suppression effects similar to PTH in rats with parathyroidectomy. The compound is currently undergoing Phase I clinical trials for the treatment of hypoparathyroidism. On December 11, Ascendis Pharma Inc. announced that the U.S. FDA had accepted the company's resubmitted New Drug Application (NDA) for palopegteriparatide (TransCon PTH) for the treatment of adult patients with hypoparathyroidism. The resubmitted application was a complete response to a Class II resubmission and set a Prescription Drug User Fee Act (PDUFA) target date of May 14, 2024.  TransCon PTH is an investigational PTH hormone prodrug developed by Ascendis Pharma. It is a mPEGylated modification of the parathyroid hormone (PTH 1-34) designed for once-daily injection to provide sustained release of active PTH. The drug is currently being developed for the treatment of adult hypoparathyroidism. Targeted PTH1R Therapy for Osteoporosis On November 21, Apotex Inc. also announced that the U.S. FDA approved the company's Teriparatide injection for the treatment of osteoporosis. The Teriparatide injection is supplied in the form of single-patient use prefilled pens, with each pen containing 250 mcg/mL and a dosage of 20 mcg per administration. On November 17, the U.S. FDA also approved the marketing of a Teriparatide injection by Teva Pharmaceuticals, similarly intended for the treatment of osteoporosis. Teriparatide is a recombinant peptide and a synthetic form of natural human parathyroid hormone. This medication can help the body to form new bone, increase bone mineral density, and strengthen bones. Abaloparatide was originally developed by Ipsen SA as an N-terminal analog of parathyroid hormone-related protein (PTHrP) and is also an agonist for the parathyroid hormone type 1 receptor (PTH1R). It is a synthetic peptide consisting of 34 amino acids and shares 41% homology with human parathyroid hormone 1-34 and human PTHrP 1-34. Following its approval in the United States in 2017, it has also been approved in countries and regions such as Japan and the European Union for the treatment of osteoporosis and postmenopausal osteoporosis.