EU Regulator Starts its Review of Cidara Therapeutics’ Candidiasis Therapy Rezafungin

The EU regulator has begun its review of Cidara Therapeutics’ once-weekly antifungal rezafungin, with a decision expected next year as a new option for serious, invasive candida infections. The application is based on the ReSTORE trial, which demonstrated that rezafungin, an echinocandin, was as effective as daily dosing with the decades-old drug caspofungin in severe candidemia and invasive candidiasis. Rezafungin, if approved, would be the first new front-line therapy for severe candida infections in well over a decade, providing a much-needed new option for patients who do not respond to current front-line drugs.

The EU filing comes shortly after Cidara and its US partner for the drug, Melinta Therapeutics, submitted rezafungin for FDA approval, with a decision expected in the first quarter of 2023. Melinta paid Cidara USD 30 million upfront for the drug’s US rights in a deal that could be worth up to USD 460 million in royalties on sales. Mundipharma now has commercial rights to the antifungal drug in all markets other than the United States and Japan because of a 2019 agreement that included a USD 30 million upfront fee, a USD 9 million equity investment, and up to USD 529 million in milestone payments and royalties.

Despite current treatments, the mortality rate for patients with invasive candidiasis is still high, reaching up to 40%. Because of this unmet need, Cidara predicts a USD 400 million market opportunity for rezafungin, which could rise to USD 750 million if the drug also performs well in the ReSPECT trial, where it is being used to prevent infections with Candida, Aspergillus, and Pneumocystis species in blood and bone marrow transplant patients.

EU Approves Gilead Sciences’ HIV Therapy Sunlenca

After the FDA rejected it earlier this year, the European Commission has become the first regulator in the world to approve Gilead Sciences’ therapy for people with multidrug-resistant (MDR) HIV infection that only needs to be taken twice a year. Sunlenca, which is based on the HIV capsid inhibitor lenacapavir, has been approved in the EU for use as an adjunct to antiretroviral therapy in patients who are unable to achieve viral suppression with current drugs. It is administered as an injection every 6 months following an initial oral dose-loading course.

Once available, it will compete with ViiV Healthcare’s Rukobia (fostemsavir), Gilead’s main HIV competitor, which was approved for MDR HIV in the EU last year and in the US in 2020 but must be taken orally every day. Rukobia earned £35 million (USD 41 million) in the first half of 2022 and £45 million overall in 2021. The FDA rejected Gilead’s first marketing application for Sunlenca in February due to manufacturing concerns, specifically the possibility of sub-visible particulate contamination from the borosilicate glass vials that were originally used to produce the drug.

Moreover, Gilead switched to an aluminosilicate glass vial and refiled the drug in June, and is now hoping for FDA approval by the end of its review period on December 27. Gilead also plans to expand the use of lenacapavir into new and larger patient populations, including the general HIV-positive population and people who have had sex with HIV-positive partners for pre-exposure prophylaxis (PrEP).

Merck Signs USD 3.5 Billion Deal with Orna Therapeutics

Merck announced a collaboration agreement to discover, develop, and commercialize multiple programs, including vaccines and therapeutics in infectious disease and oncology.

Under the terms & conditions of the agreement, Merck will make a payment to Orna of $150 million, which will be expensed by Merck itself in the third quarter 2022 and included in non-GAAP results. Additionally, Orna will be eligible to receive upto $3.5 billion in development, sales, and regulatory milestones allied with the progress of the multiple vaccine, therapeutic programs, and authorities on any approved drugs derived from the association. Orna will preserve rights to its oRNA-LNP technology platform and will extend to advance other wholly owned programs in various areas such as oncology and genetic disease. Merck will invest $100 million of equity in Orna’s recently completed Series B financing round.

By self-circularization, Orna’s proprietary oRNA technology creates circular RNAs from linear RNAs. oRNA molecules have been shown to have more excellent stability in vivo than linear mRNA and have the potential to process larger quantities of therapeutic proteins inside the body. Newly synthesized oRNA molecules are more concisely packaged into custom lipid nanoparticles, which Orna has engineered to target critical tissues in the body. 

Preclinical data, including the presentations at the 2022 American Society of Gene & Cell Therapy Annual Meeting, have showed the potential of oRNA expression and delivery as an approach for further development in multiple areas, including vaccines and oncology therapeutics.

FDA Grants Swift Review to AstraZeneca and Merck’s Lynparza 

AstraZeneca and Merck & Co’s PARP inhibitor Lynparza is previously in use to treat prostate cancer associated with a specific genetic mutation. However, it could be broadened if the FDA approves a new marketing application.

The US regulator has initiated a priority review of Lynparza in combination with abiraterone and prednisone/prednisolone as a first-line treatment for metastatic castration-resistant prostate cancer based on the results of the PROpel trial.

The study included an all-comer population of men with mCRPC showcased that Lynparza plus Johnson & Johnson’s hormonal therapy Zytiga reduced the risk of disease progression or death by 34 per cent versus Zytiga alone, with radiographic progression-free survival of 24.8 months and 16.6 months, respectively.

Lynparza was approved in 2020 as second-line therapy for homologous recombination repair (HRR) gene-mutated mCRPC last year. However, extending its label to include non-HRR patients in the frontline setting would increase the number of patients that are eligible for the treatment.

The drug was first approved in 2014, and is used for various indications across ovarian cancer, breast cancer, fallopian tube cancer, peritoneal cancer and pancreatic cancer. It remains one of AstraZeneca’s fastest-growing oncology therapies, with sales rising 18 per cent to almost $1.3 billion in the first half of this year.

The priority review indicates that the FDA targets to complete its application assessment within 6 months, and according to AstraZeneca, that should happen before the end of the year.

Prostate cancer is one of the most commonly diagnosed cancer in men, and despite an increase in the number of available treatments for men with metastatic castration-resistant prostate cancer, 5 year survival remains stubbornly low at around 15 per cent. In the United States, prostate cancer is projected to cause around 35,000 deaths in the year 2022.

The new indication would also extend Lynparza’s lead in prostate cancer over rival PARP inhibitors like GSK’s Zejula, Clovis Oncology’s Rubraca, and Pfizer’s Talzenna.

Rubraca was approved in the year 2020 for BRCA1/2 mutated mCRPC and is in two phases III trials to extend its label. These include the CASPAR study of the drug in combination with Pfizer/Astellas’ Xtandi, which consists of an all-comer mCRPC population whose tumors have become resistant to androgen-reducing first-line medicines.

GSK’s Zejula recently showed that it improved rPFS in patients with newly-diagnosed mCRPC when given alongside Zytiga and prednisone in the MAGNITUDE trial. Still, its benefits were confined to patients with homologous recombination repair mutations only.

Meanwhile, Pfizer’s Talzenna has been paired with Xtandi in phase III TALAPRO-II trial, in patients suffering with and without homologous recombination repair mutations, with results awaited later this month.

FDA Approves Axsome’s Depression Therapy Auvelity

Axsome Therapeutics has updated that the US FDA has approved AUVELITYTM (dextromethorphan HBr -bupropion HCl) extended-release tablets for the treatment of the Major Depressive Disorder (MDD) in adults. 

AUVELITY is the first, only approved oral N-methyl D-aspartate (NMDA) receptor antagonist medicine to treat Major Depressive Disorder. The therapy has a statistically significant antidepressant efficacy compared to a placebo starting at one week. The rapid antidepressant effects of AUVELITY have been sustained at all subsequent time points. AUVELITY uses the first new oral mechanism of action in more than 60 years for MDD. 

In the clinical trials, AUVELITY was studied in a GEMINI placebo-controlled study in more than 1,100 patients with depression. In the study, AUVELITY demonstrated superior results compared to placebo in improving depressive symptoms as measured by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6. AUVELITY works on the NMDA receptor, an ionotropic glutamate receptor, and the sigma-1 receptor in the brain via its dextromethorphan component.

Based on preliminary clinical data, in March 2019, the FDA granted Breakthrough Therapy designation for AUVELITY to treat Major Depressive Disorder. Additionally, the therapy was evaluated by the FDA under Priority Review. As per the initial updates, AUVELITY is expected to be commercially available in the U.S. in the fourth quarter of 2022. 

Major Depressive Disorder is a debilitating, chronic, biologically-based disorder that results in a low mood and energy and is often accompanied by other emotional and physical symptoms. As per WHO, MDD affects 322 million people globally, representing an 18.4% increase in the number of people living with Major Depressive Disorder between 2005 and 2015. According to the U.S. Department of Health and Human Services, an estimated 21 million U.S. adults experience Major Depressive Disorder each year. Apart from Axsome, several key companies such as Allergan (Cariprazine), SAGE Therapeutics (SAGE-217), Seelos Therapeutics (SLS-002), Clexio Biosciences (CLE-100), and others are evaluating their Major Depressive Disorder therapies.

European Commission Approves Oncopeptides’ Pepaxti in Combination with Dexamethasone for Multiple Myeloma

Oncopeptides AB has announced that the European Commission has granted marketing authorization to its therapy Pepaxti® (melphalan flufenamide, also called melflufen) in combination with dexamethasone, for the treatment of multiple myeloma in adults. The marketing authorization is valid in all EU member states and the European Economic Area (EEA), including Iceland, Lichtenstein, and Norway. Oncopeptides is looking forward to launching the therapy in Germany in Q4, 2022, ahead of an EU-wide rollout.

Pepaxti (melphalan flufenamide, also called melflufen) is a lipophilic peptide conjugated alkylating drug that rapidly and selectively delivers cytotoxic agents into tumor cells. The drug is composed of a di-peptide and an alkylating moiety. The therapy is approved only for patients who have received at least three prior lines of therapies, whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody. The drug is also approved to treat patients who have demonstrated disease progression on or after the last therapy. 

EU approval of Pepaxti was based on the key findings observed in the Phase II HORIZON study and the randomized controlled Phase III OCEAN study. On July 20, 2022, the FDA announced a public advisory meeting of the Oncologic Drugs Advisory Committee on September 22, 2022, to discuss the benefit/risk of melphalan flufenamide. 

Multiple Myeloma is one of the most common hematologic malignancies that originates in plasma cells, a type of white blood cell, and accounts for approximately 1-2% of all new cancer cases. The global incidence rate of Multiple Myeloma is observed to be 1.7 per 100,000. According to DelveInsight’s assessment, among the EU-5 countries, in 2020, Germany registered the highest number of cases of Multiple myeloma with 7,600 cases.

Bluebird Bio’s Zynteglo Becomes First Cell-based Gene Therapy to Approve in the US

Bluebird Bio’s Zynteglo became not only the first but the most expensive gene therapy after it is by the US FDA on Wednesday. Also known as Beti-cel, Zynteglo is a one-time gene therapy that is custom-designed to treat beta-thalassemia in adult and pediatric patients. Majorly those who require blood transfusions at regular intervals. 

The gene therapy nearly took 10 years of development. Zynteglo is launched at a price tag of approximately USD 2.8 million. The therapy offers advanced treatment by providing a reliable alternative to regular red blood cell transfusions and iron chelation. Beta-thalassemia is a rare disorder causing hypoxia in patients’ bodies, commonly leading to liver and heart complexity. 

The drug is expected to face some complications from insurers due to its high pricing. Bluebird has been pitching Zynteglo in order to secure a one-time therapy that can comply with the transfusion demands. It’ll ultimately aid in saving patients over a long period of time. 

The average cost for a single transfusion is approximately 6.4 million USD. Since the treatment comes with a high cost, up to 80% of that payment will be refunded if a patient does not achieve transfusion independence. The launch of the treatment is expected in the fourth quarter. Almost negligible revenue is expected till the end of 2022 since the treatment cycle is approximately 70 to 90 days, starting from the first cell collection to the final transfusion. 

GSK Gets June 2023 FDA Decision Date for Momelotinib

US Food and Drug Administration (FDA) approved GlaxoSmithKline Plc’s New Drug Application (NDA) for Momelotinib. The drug comprises a differentiated mechanism of action for treating anemic patients with myelofibrosis. As per the reports US FDA assigned 16 June 2023 for Prescription Drug User Fee Act Action. 

The approval of NDA is based on the outcomes of major Phase III trials. The Momentum trial of the drug Momelotinib passed all the requirements, including primary and key secondary endpoints, which majorly comprised Splenic Response Rate (SRR), Transfusion Independence (TI) rate, and Total Symptom Score (TSS). The final analysis data of the trial for the drug was preset at the 2022 American Society of Clinical Oncology Annual Meeting and the European Hematology Association 2022 Hybrid Congress.

The final approval of the market for Momelotinib is yet to be announced.  Momelotinib was initially developed by Sierra Oncology, Inc., which GlaxoSmithKline Plc further occupied in July 2022. Myelofibrosis is a rare condition causing hematologic cancer majorly due to dysregulated JAK-signal transducer and activator of transcription protein signaling. The major symptoms of myelofibrosis include splenomegaly and progressive anemia. 

Myelofibrosis is known to affect approx 20,000 patients in the US, including which 40% of the patients are pre-diagnosed with anemia, and the remaining patients develop anemia gradually. The major cause behind 30% of patients discontinuing the treatment is the lack of enough blood inside the body. The patients might also need to undergo multiple transfusions as a part of treatment.