PharmaShots Interview: Astellas' Txema Sanz Shares Insights on the Evrenzo (roxadustat) for Symptomatic Anemia Associated with Chronic Kidney Disease

In an interview with PharmaShots, Txema Sanz, Senior Vice President and Head of the Global Medical Specialties at Astellas shared his views on the EC's approval of Evrenzo (roxadustat) for the Treatment of symptomatic anemia associated with Chronic Kidney Disease

Shots:

The approval is based on the P-III program including 8 studies evaluating Evrenzo in 9600 patients with symptomatic anemia associated with CKD, regardless of dialysis status & prior ESA treatment. Following the EC's approval, FibroGen to receive $120M milestones along with royalties based upon EU sales
The results demonstrated that the therapy was effective in maintaining target Hb levels & safety profile is reflective for CKD populations compared to ESAs
Roxadustat is a HIF-PH inhibitor & is approved in EU member states, including the EEA countries, Japan, China, Chile & South Korea for the same indication in adult patients on DD & NDD

Tuba: Discuss in brief, CKD, and anemia of CKD along with its epidemiology.

Txema Sanz: Chronic kidney disease (CKD) is a highly prevalent and underdiagnosed condition, affecting approximately one in 10 people globally. It is recognized as a global public health issue and is projected to become the fifth most common cause of premature death by 2040.

Anemia is a common and early complication of CKD affecting approximately 20% of CKD patients.

Multiple factors cause anemia of CKD, including reduced oxygen sensing in the kidney, reduced erythropoietin production, chronic inflammation that results in increased hepcidin levels, and iron deficiency.

Anemia of CKD has a significant negative impact on patients' everyday lives, reducing their ability to exercise, work and perform everyday tasks. Additionally, anemia of CKD is associated with an increased risk of hospitalization, cardiovascular (CV) complications, and worsening kidney function.

Despite this many patients with anemia of CKD remain untreated or undertreated, in part due to the complexities of current treatment approaches.

Tuba: Give a brief description of EVRENZO's work with the HIF-PH family.

Txema Sanz: Astellas is very pleased EVRENZO (roxadustat) has been approved as the first orally administered hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitor and believes it offers an important new therapeutic option for the management of symptomatic anemia in adults with CKD in the EU.

The research teams that first identified the HIF protein complex and the way the body responds to low oxygen, were awarded the Nobel Prize in 2019 for their work. This award-winning discovery is the target pathway, integral to the mechanism of action of roxadustat

Oral EVRENZO supports the management of anemia by increasing hemoglobin (Hb) levels through a different mechanism of action (MoA) compared with the current standard of care, injectable erythropoiesis-stimulating agents (ESAs), which are typically co-administered with IV iron.

As a HIF-PH inhibitor, EVRENZO activates the body's natural response to reduced oxygen levels in the blood.
This response involves the regulation of multiple, coordinated physiological processes that leads to increased stimulation of red blood cell production and increased availability of iron thus providing anemia management with a reduced need for IV iron.

Tuba: Summarize the journey of EVRENZO's clinical study. What benefits of EVRENZO have been shown in studies?

Txema Sanz: The European Commission's decision and the recent approval in the UK are based on the results from a comprehensive pivotal P-III program comprising eight multicenter and randomized studies, which involved 9,600 patients worldwide.

The results of the roxadustat clinical program support the efficacy of roxadustat in achieving and maintaining target Hb levels (10'12 g/dL) in patients with anemia of CKD regardless of dialysis status and irrespective of prior ESA treatment with a reduced need for IV iron.

The safety profile observed in the roxadustat development program is reflective of the CKD populations studied and comparable with ESAs.

Tuba: Are you planning for the study of drugs on some other type of anemia?

Txema Sanz: In August 2019, Astellas' co-development partner FibroGen initiated a P-II study in the U.S. investigating the efficacy and safety of roxadustat for the treatment of anemia in patients receiving chemotherapy for non-myeloid malignancies.

For more information about this study, visit www.clinicaltrial.gov [NCT04076943]

Roxadustat is in P-III development for the treatment of anemia in patients with myelodysplastic syndromes (MDS).

Tuba: Can we have a discussion on the Rx+ healthcare solution? How can it be helpful to the patients?

Txema Sanz: At Astellas, Changing Tomorrow is the ethos that guides everything we do. We combine promising science and the latest technology with our expertise and passion to make a difference, to deliver treatments and solutions that improve the lives of patients.

Our Rx+ story defines the type of society we want to realize through Rx+, the VALUE provided by it, as well as the business domains associated with this area.

We have identified key areas and priorities for Rx+, with the aim of realizing a world where people can live mentally and physically healthy lives and be true to themselves through healthcare solutions based on scientific evidence.

Our three core VALUES include:

Preventing disease onset and slow progression by using personal data
Expanding options for people with limited access to current therapeutics
Supporting active living by enhancing physical and sensory function

Several Rx+ programs are steadily progressing within our six established areas: (1) Chronic Disease Progression Prevention; (2) Motor Function Support/Replacement; (3) Digital × Neuroscience; (4) Patient w/o Effective Medicines; (5) Patient Outcome Maximization via Precise Surgery/Diagnosis; and (6) Sensory Function Support/Replacement.

Tuba: How much EVRENZO sparked the economy of Astellas after the approval of EC? Do you think the product will boost more?

Txema Sanz: EVRENZO is an important medicine within our specialty care business and we hope that it will contribute to the management of the anemia of CKD in many patients worldwide. Current projected sales (potential peal sales) are between 50 and 100 billion yen in Astellas territories only.

Tuba: Can you shed some light on Astellas' contribution to the healthcare sector?

Txema Sanz: At Astellas, we are working to turn innovative science into value for patients. Our research focuses predominantly on areas of high unmet need in under-served and serious diseases.

Our current R&D pipeline focuses on four key areas such as immune-oncology, genetic regulation (mainly for muscle diseases), regeneration (cell therapy mainly for ophthalmology), and mitochondrial biology (mainly for renal and muscle diseases).

In October 2019, - the U.S. Food and Drug Administration (FDA) granted Astellas Fast Track designation for treatments focused on patients at increased risk of developing moderate to severe acute kidney injury (AKI) after coronary artery bypass and/or valve surgery. Phase II a PoC study in cardiovascular surgery-associated AKI is ongoing.

Astellas also has a number of oncology assets in late-stage trials, including:

XTANDI® (enzalutamide) for the treatment of patients with castration-resistant prostate cancer (CRPC) in many countries. It is also approved for metastatic hormone-sensitive prostate cancer (mHSPC, also known as metastatic castration-sensitive prostate cancer or mCSPC) in the EU, U.S., and Japan.
XOSPATA® (gilteritinib) for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with FLT3 mutation. Gilteritinib is currently being investigated for earlier stages of AML.
PADCEVTM (enfortumab vedotin-ejfv), co-developed with Seagen, is approved in U.S. and Japan for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received prior therapy. PADCEV is currently being investigated for earlier stages of urothelial cancer as well as other solid tumors.
Zolbetuximab, is being investigated in gastric and gastroesophageal junction (GEJ) adenocarcinoma, as well as pancreatic adenocarcinoma.

In addition, Astellas has non-oncology assets in late-stage trials, including:

Fezolinetant for the treatment of moderate-to-severe vasomotor symptoms.
AT132 for the treatment of X-linked myotubular myopathy.

Source: WhatIsEpigenetics

About Author: Txema Sanz is the Senior Vice President and Head of Global Medical Specialties at Astellas. He has completed D.Phil. Neuroscience from the University of Oxford & has more than 20 years of industry experience. Sanz will continue to provide leadership for the global teams supporting priority non-oncology products, excluding Gene/Cell Therapies.