Daiichi Sankyo Receives the First Approval for its Blood Cancer Drug Ezharmia

Daiichi Sankyo has received the first global approval for Ezharmia, a first-in-class dual EZH1 and EZH2 inhibitor for the treatment of patients with relapsed or refractory adult T-cell leukemia/lymphoma (ATL). The Japanese Ministry of Health, Labour, and Welfare (MHLW) approved Ezharmia (valemetostat tosylate) based on the findings of an open-label phase II trial that revealed a 48% overall response rate in previously treated ATL patients.

ATL is a rare and highly aggressive form of non-Hodgkin lymphoma (NHL) that is generally associated with HTLV-1 retrovirus infection and can manifest as either lymphoma or leukemia. It is usually treated with chemotherapy, but it has a high relapse rate and a five-year survival rate of 12% to 14%.

Japan is a global hotspot for ATL cases, with an estimated incidence of around 27 cases per 100,000 people, far higher than the United States, where the rare cancer is thought to have an incidence of around 0.05 cases per 100,000 people, with around 1,000 new cases diagnosed each year. Cancer is also more common in the Caribbean islands, Central and South America, Africa, and the Middle East.

Other drugs used to treat ATL include Kyowa Kirin’s amti-CCR4 antibody Poteligeo (mogamulizumab), which was approved by the MHLW in 2012 for CCR4-positive ATL, and Bristol-Myers Squibb/oral Celgene’s therapy Revlimid (lenalidomide), which was approved 5 years ago.

“As the first dual inhibitor of EZH1 and EZH2 to receive regulatory approval anywhere in the world, EZHARMIA represents an important advancement in the treatment of patients with relapsed or refractory adult T-cell leukemia/lymphoma, who have very few options beyond intensive chemotherapy,” said Wataru Takasaki, PhD, Executive Officer, Head of R&D Division in Japan, Daiichi Sankyo. 

He further added, “We are proud to have successfully translated the science behind dual EZH1 and EZH2 inhibition into a new and novel therapy for these patients, who face a poor prognosis and represent one of the most significant unmet medical needs in Japan. We will continue to pioneer the approach in the global development of EZHARMIA, our fifth new oncology medicine approved in Japan in the past three years.” 

Other EZH2 inhibitors that have completed clinical trials include MorphoSys’ lirametostat (CPI-1205) and GSK’s GSK2816126, both of which reached mid-stage testing but appear to have been abandoned. Another SHR2554 from Jiangsu Hengrui Medicine is still in the early stages of clinical development.

Pfizer and Sangamo Restarts Trial for Hemophilia A Gene Therapy giroctocogene fitelparvovec

After the FDA lifted a clinical hold on the study, Pfizer and Sangamo resumed patient recruitment in their registration trial for the hemophilia A gene therapy giroctocogene fitelparvovec. The phase III AFFINE trial was voluntarily halted by the two partners nearly a year ago and then placed on hold by the FDA after patients receiving the therapy produced higher than expected levels of Factor VIII – the clotting factor that giroctocogene fitelparvovec is designed to produce in the body.

Following treatment, some patients in the study had Factor VIII activity greater than 150%, raising concerns that they may be at increased risk of harmful clotting events. To reduce the risk, some patients were given oral anticoagulants.

The program’s postponement allowed rival hemophilia to emerge. BioMarin, a gene therapy developer, is poised to overtake Pfizer and Sangamo, particularly in Europe, where it recently received conditional approval for its therapy valoctocogene roxaparvovec from the European Commission. 

However, BioMarin has experienced its own development delays, with the FDA rejecting the therapy’s marketing application – known as Roctavian in the EU – in 2020, with a request for more information on its durability. BioMarin has stated that it intends to reapply for approval in the United States this month. That timeline puts BioMarin well ahead of Pfizer and Sangamo, who now predicts that dosing in AFFINE will begin next month, with results expected in the first half of 2024.

FDA Grants Accelerated Approval to Eli Lilly’s RET Drug Retevmo

Eli Lilly was granted FDA approval for its drug RET Drug Retevmo on September 21, 2022. The approval was granted for adult patients possessing locally advanced or metastatic tumors. The therapy is being used for tumors possessing the RET gene where there are limited options for alternative treatments. 

As many as 41 patients were evaluated, and their efficacy was demonstrated in LIBRETTO-001 (NCT03157128), which is a multicenter, open-label, and multi-cohort trial. The evaluation was done based on results obtained from around 343 patients (RET fusion-positive). Patients were administered selpercatinib until the symptoms of disease progression and susceptible toxicity were observed. 

As per the Blinded Independent Review Committee (BIRC), the overall response rate (ORR) and duration of response (DOR) were recorded to determine efficacy. The recorded ORR and DOR recorded for 41 respective patients were 44% (95% CI: 28, 60)  and (95% CI: 9.2, not estimable) in the duration of 24.5 months. The key tumor types with visible responses include pancreatic adenocarcinoma, colorectal, salivary, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma. The trial results showed the most common adverse reactions (≥25%) in patients, mainly edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.

GSK and Spero Therapeutics Announce Exclusive License Agreement for Late-Stage Antibiotic Asset, Tebipenem HBr

Tebipenem pivoxil hydrobromide (tebipenem HBr) is about to commercialize after GSK and Spero announced the exclusive license agreement. The late-stage antibiotic therapy is about to commercialize in all regions except for Japan and certain other Asian provinces. The development of the antibiotic is being done by Spero. Tebipenem HBr is a potential first oral carbapenem antibiotic used to treat bacterial urinary tract infections (cUTI), including pyelonephritis. Luke Miels, Chief Commercial Officer, GSK, said: “There is a high unmet medical need for a novel oral antibiotic as an alternative to intravenous hospital therapy for drug-resistant complicated urinary tract infections. Tebipenem HBr complements GSK’s infectious disease strategy and is consistent with our commitment to finding value-enhancing opportunities to build a strong late-stage portfolio. Tebipenem HBr has a clear US FDA regulatory path to potential approval, which could significantly benefit patients with complicated urinary tract infections.”

“Spero’s agreement with GSK provides a critical step towards fully realising the value tebipenem HBr can potentially provide to physicians, payors, and patients,” said Ankit Mahadevia, M.D., Chief Executive Officer of Spero. “We are thrilled to collaborate with GSK on developing tebipenem HBr for patients suffering from complicated urinary tract infections. With their antibiotic expertise and global commercial reach, GSK is ideally positioned to launch tebipenem HBr following regulatory approval as the first oral treatment for complicated urinary tract infections, providing patients with an alternative to in-hospital intravenous therapy. Tebipenem HBr’s potential as an at-home, oral option can potentially be of significant benefit by reducing hospital resource utilisation. In addition, our partnership with GSK strengthens our balance sheet and shareholder base.”

The phase III clinical trial will be initiated in 2023 by Spero, considering the feedback provided by US FDA. GSK will make an initial investment of $66 million following the terms of the license agreement. The complete payment will be made based on milestones. 

European Commission Approves AstraZeneca’s Tezspire for Severe Asthma

AstraZeneca’s Tezspire, also known as Tezepelumab, has been approved in the European Union as an add-on maintenance treatment in patients of age 12 years and older suffering from severe asthma who are partially controlled with high dose inhaled corticosteroids plus another medicinal product.

Tezspire is a maintenance therapy for patients suffering from no phenotype or biomarker limitations.

This approval was based on results from the clinical study, PATHFINDER, which included the pivotal NAVIGATOR phase III trial in which Tezspire showed superiority across every other primary and key secondary endpoint in patients suffering from severe asthma compared to placebo when added to standard therapy.

Tezspire is the first biologic that has been approved in Europe for people suffering from severe asthma that acts at the top of the inflammatory cascade by blocking thymic stromal lymphopoietin. Further, the treatment significantly reduced asthma worsenings across the PATHWAY phase II and the NAVIGATOR phase III clinical trials, which consisted of a broad population of severe asthma patients irrespective of key biomarkers.

FDA Approves Selpercatinib for Locally Advanced or Metastatic RET Fusion+ Solid Tumors

Patients suffering from RET fusion-positive locally advanced or metastatic solid tumors can now acquire treatment with selpercatinib following its approval by the FDA.

Selpercatinib has been approved by the FDA at an oral dose of 40 mg and 80 mg for patients with RET fusion-positive locally advanced or metastatic solid tumors following progression on or after previous systemic therapy with no other adequate treatment options.

The continued approval of selpercatinib in this indication may depend on confirmation of clinical benefit from a trial. The phase I/II LIBRETTO-001 trial included a total of around 40 patients suffering from solid malignancies, with the most common tumor types such as pancreatic adenocarcinoma, colorectal cancer, salivary gland cancer, and unknown primary disease. The overall response rates in each tumor type were approximately 55%, 20%, 50%, and 33%, respectively. 

“In the LIBRETTO-001 trial, selpercatinib showed clinically meaningful and durable responses across a variety of tumors in patients suffering with RET-driven cancers, including pancreatic, colon, and other cancers in need of new treatment options,” added Vivek Subbiah, MD, associate professor of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center. 

Fennec Pharmaceuticals Announces FDA Approval of PEDMARK® (Sodium Thiosulfate Injection)

On September 21, 2022, Fennec Pharmaceuticals Inc. announced that the US FDA had approved its therapy, PEDMARK® (sodium thiosulfate injection). PEDMARK® is designed to reduce the risk of ototoxicity associated with cisplatin in pediatric patients one month of age and older with localized, non-metastatic solid tumors. With this approval, the PEDMARK becomes the first and only treatment approved by the FDA to reduce cisplatin-related ototoxicity in pediatric patients. PEDMARK® consists of a unique formulation of sodium thiosulfate in single-dose, ready-to-use vials for intravenous use.

The FDA decision was based on the safety and efficacy data from two pivotal multicenter, open-label, randomized Phase 3 trials (SIOPEL 6 and COG ACCL0431). The clinical trials compared PEDMARK plus cisplatin-based regimens to cisplatin-based regimens alone to reduce cisplatin-induced hearing loss in pediatric patients. In the SIOPEL 6 trial, 114 patients were enrolled from 1 month to 18 years of age with standard risk hepatoblastoma. In the COG ACCL0431 trials, 125 patients from 1 to 18 years of age with solid tumors were enrolled for the study. Both the study demonstrated that the incidence of hearing loss was consistently and significantly lower in the PEDMARK plus cisplatin arm compared with the cisplatin alone arm. The most common adverse reactions in SIOPEL6 are vomiting, infection, nausea, decreased hemoglobin, and hypernatremia. The most common adverse reaction in COG ACCL0431 is hypokalemia. The approval of PEDMARK® is expected to overcome the unmet needs and prevent platinum-induced ototoxicity in pediatric patients.

FDA Approves UBE Corp and Santen’s Omlonti Eye Drops for Glaucoma Patients

On September 26, 2022, Santen Inc. and UBE Corporation (UBE) announced that the US FDA had approved their therapy, OMLONTI® (omidenepag isopropyl ophthalmic solution) 0.002% eye drops, for the reduction of elevated intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension. OMLONTI® is developed in collaboration by Santen and UBE.

The therapy was evaluated in three randomized and controlled clinical trials in subjects with open-angle glaucoma or ocular hypertension with an average baseline IOP of 24-26 mm Hg. Omidenepag isopropyl, the active pharmaceutical ingredient in OMLONTI®, is a selective prostaglandin EP2 receptor agonist developed by UBE. Omidenepag isopropyl increases aqueous humor drainage through the conventional (or trabecular) and uveoscleral outflow pathways and is the only product with this pharmacological action in the market available currently. 

Earlier in 2018, the OMLONTI® was launched in Japan as Eybelis® ophthalmic solution 0.002%. At the beginning of February 2021, the therapy was released in five Asian countries and regions. Glaucoma is a severe disease that damages the optic nerve, resulting in visual field loss. It is one of the leading causes of irreversible blindness worldwide. In 2020, nearly 76 million people were affected by it and the number of cases are further expected to reach 95 million by 2030. Additionally, more than three million people in the United States are affected by glaucoma or ocular hypertension. It is observed that primary open-angle glaucoma is the most common type of glaucoma. With the launch of OMLONTI® as a new option to control IOP, the glaucoma therapeutics market outlook is expected to improve immensely in the coming years.