Byondis Files its HER2-Targeting Antibody-Drug Conjugate (ADC) Trastuzumab Duocarmazine in the US and Europe

Byondis has filed for clearance of its HER2-targeting antibody-drug conjugate (ADC) trastuzumab duocarmazine in the United States and Europe, setting up a battle with heavyweight competitors Roche and AstraZeneca/Daiichi Sankyo next year. The Dutch company submitted the ADC to the FDA last week, and yesterday, the company said that the EMA had formally begun its review of the drug for HER2-positive, locally advanced or metastatic breast cancer that cannot be treated surgically. Byondis believes trastuzumab duocarmazine (SYD985) is a “next-generation” anti-HER2 ADC with a lower toxicity profile than competitors like Roche’s Kadcyla (adotrastuzumab emtansine) and AZ/Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan). 

This is due to the company’s ADC technology platform, which implies that the cytotoxic payload that circulates systemically after treatment is lower than that of currently-marketed ADCs, limiting adverse effects. The ADC is stable in the bloodstream and is internalized by cancer cells, where the payload (duocarmycin) is activated, limiting the drug’s exposure to healthy tissues. The marketing applications were filed in the US and EU based on the results of the phase III TULIP trials, which compared trastuzumab duocarmazine to the physician’s choice of therapy following at least two prior HER2-targeting treatment regimens, with an application in the US due soon.

The physician’s choice of therapy included Seagen’s oral HER2 drug Tykerb (lapatinib) plus Roche’s chemotherapeutic drug Xeloda (capecitabine) or Roche’s HER2 therapy Herceptin (trastuzumab) plus one of Xeloda, vinorelbine, or eribulin. The FDA has assigned trastuzumab duocarmazine a typical 10-month review duration in the United States. Byondis has teamed with German pharmaceutical company Medac to commercialize the drug in Europe.

AbbVie Files Migraine Prevention Drug Atogepant in EU

AbbVie has submitted its oral CGRP inhibitor atogepant for the prevention of both episodic and chronic migraine in the EU, attempting to catch up with Pfizer/BioHaven and their recently authorized Vydura drug. The EMA file for atogepant covers migraine prevention in people who experience at least four migraine days per month – the same indication that was approved for Vydura (rimegepant) in April as the first oral medication for migraine prevention.

In the United States, Atogepant was licensed as Qulipta last September for migraine prevention. In contrast, Vydura is marketed as Nurtec ODT and was cleared for acute migraine therapy in early 2020 and for prevention in May 2021. AbbVie sells another oral CGRP called Ubrelvy (ubrogepant) for acute migraine treatment, which produced roughly USD 552 million last year, but hasn’t yet published Qulipta’s quarterly sales performance. Meanwhile, Biohaven reported Nurtec ODT sales of USD 462 million in 2021, prompting Pfizer to pay USD 500 million upfront for the drug’s rights outside the US in November.

Last month, the drugmaker revealed new evidence with atogepant in the prevention of chronic migraine – defined by the FDA as at least 15 migraine days per month for at least three months – that AbbVie suggests could help it differentiate atogepant from its competitor.

Grünenthal Acquires Bayer’s Testosterone Drug Rights for €500 Million

Grünenthal is paying up to €500 million for rights to Nebido (testosterone undecanoate), sold in around 80 countries worldwide for a testosterone deficiency, and made €117 million last year.

The legacy product now lies outside Bayer’s core areas of oncology, cardiology, ophthalmology, hematology, radiopharmaceuticals, and women’s health, and the funds raised from the sale will support the “ongoing transformation of Bayer’s pharmaceutical business to focus on the key areas of the future medical innovation,” said the company.

Fellow German group Grünenthal is a pharma company focused mainly on pain products, although its portfolio also includes other specialty medicines such as Nexium for gastrointestinal disorders.

It has a history of buying mature brands from other pharmaceutical companies, for instance paying $300 million for rights to AstraZeneca’s migraine therapy Zomig in a similar deal five years ago.

Grünenthal will purchase cash upfront, with the final figure dependent on any closing adjustments. It will also take ownership of a contract business in the United States, where Endo Pharmaceuticals licenses Nebido from Bayer and sells it under the brand name, Aveed.

The two companies said that the transaction is expected to close by the end of 2022, subject to approval by the competition authorities.

The divestment comes as Bayer is engaged in a push to become a top ten oncology company by 2030. Prostate cancer treatment Nubeqa drives its ambition, recently tipped to become a €3 billion seller.

The group faces competition from big-selling pharma products Eylea for ophthalmic diseases and anticoagulant Xarelto in the coming years. It is pivoting to growth areas to ride out that revenue loss.

Nubeqa is one of three drugs the company hopes to help weather that impact on revenues, along with recently-approved diabetic kidney disease therapy Kerendia and elinzanetant for menopausal symptoms.

Vertex Acquires ViaCyte for USD 320 Million

Vertex Pharmaceuticals recently announced that it would acquire ViaCyte, a private cellular therapy company, for $320 million. Vertex’s acquisition of ViaCyte gives it access to complementary technologies to pursue novel stem cell-derived cell replacement therapies as a functional treatment cure for type 1 diabetes.

Vertex is currently engaged in clinical trials for VX-880, an investigational allogeneic stem cell-derived, fully differentiated, insulin-producing islet cell therapy for T1D. According to a company press release, it has seen promising safety and efficacy results from its ongoing Phase I/II study.

Vertex’s acquisition of ViaCyte grants them complementary assets to accelerate the development of VX-880. These include additional human stem cell lines, intellectual property around stem cell differentiation, and good manufacturing practice manufacturing facilities for cell-based therapies.

“VX-880 has successfully showed clinical proof of concept in type 1 diabetes, and the procurement of ViaCyte will advance our goal of transforming, if not curing type 1 diabetes by expanding our capabilities and bringing additional tools, technologies, and assets to our current stem cell-based programs,” added Reshma Kewalramani, president and CEO, Vertex.

Kyowa Kirin Drops Nourianz follow-up KW-6356 for Parkinson’s

Kyowa Kirin has announced that it had dropped the development of its Parkinson’s disease therapeutics candidate, KW-6356, despite positive proof-of-concept results in a mid-stage trial. KW-6356 is a drug of the adenosine A2A receptor antagonist class, and in the phase 2 data, the drug has depicted promising results as monotherapy and, in a combo, to treat Parkinson’s disease. Kyowa Kirin started the development of KW-6356 as a follow-up to Nourianz (istradefylline), the Kyowa’s first-gen adenosine A2 agonist. The USFDA approved Nourianzby in 2019. KW-6356 has a higher affinity and selectivity for adenosine A2A receptors, and upon approval from the regulatory authorities, the therapy is expected to cover a wider group of Parkinson’s patients than Nourianz.

Kyowa Kirin cited the “global regulatory landscape, development hurdles, and timelines for potential market entry” as the key factor that makes an additional investment into the therapeutics development of KW-6356 as untenable and unsustainable. Kyowa further stated in the press release stated that clinical factors are not the issue for the decision and the therapy was potentially effective in relieving motor and non-motor symptoms. In August 2018, Kyowa Kirin, armed with positive proof-of-concept data, said it would continue to pursue development on its own.

FDA Grants Orphan Drug, Fast Track Designations to CV-01 in Recurrent Glioblastoma

The U.S. Food and Drug Administration (FDA) has granted both Orphan Drug and Fast Track Designations to Alpheus Medical’s CV-01 delivery of sonodynamic therapy (SDT) as a potential treatment for patients with recurrent Glioblastoma. Alpheus Medical’s proprietary, investigational SDT is a noninvasive drug-device combination that targets cancer cells throughout the entire hemisphere using low-intensity, diffuse ultrasound. The sonodynamic therapy is administered in an outpatient setting and does not require imaging. 

Currently, Northwell Health’s North Shore University Hospital in Long Island, New York, is enrolling patients for a first-in-human, phase 1 clinical trial evaluating the safety, optimal dosage, and efficacy of the sonodynamic therapy platform for recurrent high-grade glioma. The trial is expected to enroll up to 33 patients.

Glioblastoma is one of the most common primary brain cancer and accounts for nearly 57% of all gliomas and 48% of all primary malignant central nervous system (CNS) tumors. Currently, there are only a few effective options in the Glioblastoma Therapeutics Market. Alpheus Medical’s CV-01 is expected to change the landscape of high-grade glioma and the patient outcome.

Merck and Orion Announces USD 290 Million Collaboration for Prostate Cancer Therapy

Merck and Orion announced global collaboration for the development and commercialization of Orion’s investigational candidate ODM-208 which is an investigational steroid synthesis inhibitor for the treatment of Metastatic Castration-Resistant Prostate Cancer. The drug targets cytochrome P450 11A1 (CYP11A1), an enzyme important in steroid production. ODM-208 is supposedly an oral, non-steroidal, selective inhibitor of the CYP11A1 enzyme currently being evaluated in Phase 2 clinical trial for Metastatic Castration-Resistant Prostate Cancer treatment. By inhibiting CYP11A1 enzyme activity, ODM-208 is designed to suppress the production of all steroid hormones and their precursors that may activate the androgen receptor signaling pathway.

Merck will make an upfront payment to Orion of about USD 290 million, which will be expensed by Merck in the third quarter of 2022 and included in non-GAAP results. Orion will be solely responsible for manufacturing the clinical and commercial supply of ODM-208. In addition, the contract provides both parties with an option to convert the initial co-development and co-commercialization agreement into a global exclusive license to Merck. Orion would be eligible to receive milestone payments associated with progress in the development and commercialization of ODM-208 and tiered double-digit royalties on sales if the product is approved. The total amount potentially accrued from multiple regulatory and sales milestone events represents a substantial opportunity for Orion.

Worldwide, Prostate cancer is the second most common cancer in people assigned male at birth, with an estimated 1.4 million patients diagnosed worldwide in 2020. Approximately 10-20% of patients with advanced prostate cancer are estimated to develop CRPC within five years, and at least 84% of these patients may develop metastases at the time of CRPC diagnosis. Patients with advanced prostate cancer have a particularly poor prognosis, and the five-year survival rate remains low.

Verve Starts Trials of Cholesterol Drug in Test of Base Editing Technique

Verve Therapeutics has initiated dosing patients in a Phase 1b trial of its in vivo gene-editing drug for high cholesterol, made to permanently switch off the PCSK9 gene with a one-shot treatment. The clinical trial, namely heart-1 study, is enrolling patients with an inherited form of very high cholesterol – heterozygous familial hypercholesterolaemia (HeFH) – that predisposes them to the early development of heart disease. The first subject is administered with the dose of VERVE-101, the first test in humans of an experimental CRISPR/Cas9 genome editing technique known as base editing. Via base editing, drugs replace a single nucleotide in the DNA strand with another without making double-strand breaks (DSBs) in the gene.

The clinical trial heart-1 will enroll 40 adults with HeFH and established atherosclerotic cardiovascular disease, initially in New Zealand, although the plan is to expand the study to include investigation sites in the UK and US later this year, subject to regulatory consent. It will look at the effects of VERVE-101 on levels of PCSK9 and LDL cholesterol (LDC-c) in the blood, with the first data expected next year.

After the development process, VERVE-101 could provide a one-off alternative to a lengthening list of PCSK9 inhibitors that have to be dosed chronically. The first antibodies to reach the market were Amgen’s Repatha (evolocumab) and Sanofi/Regeneron’s Praluent (alirocumab) – which were launched several years ago . Verve’s trial could add another candidate into the mix, but for now, the attention is on establishing base editing as a therapeutic strategy.