US – Pfizer and Arvinas, a clinical-stage biopharmaceutical company, agree to a collaborative deal that will see both companies work towards the development of breast cancer therapy.
The collaboration combines Arvinas’ investigational estrogen receptor-targeting breast cancer therapy with Pfizer’s deep experience in breast oncology therapeutics.
Under the pact, Arvinas is set to receive US$650 million in an upfront payment, in addition to a potential US$1.4 billion in milestone payments; profits and costs to be shared 50/50 worldwide. Additionally, Pfizer expects to complete a US$350 million equity investment in Arvinas.
Arvinas is developing ARV-471, an investigational oral PROteolysis TArgeting (PROTAC) Chimera estrogen receptor protein degrader. The estrogen receptor is a well-known disease driver in most breast cancers.
ARV-471 is currently in a Phase 2 dose expansion clinical trial for the treatment of patients with estrogen receptor (ER) positive / human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) locally advanced or metastatic breast cancer.
“This collaboration has the potential to be transformational, as it combines our leadership in targeted protein degradation with Pfizer’s global capabilities and deep expertise in breast cancer. This should significantly enhance and accelerate the development and potential commercialization of ARV-471 while also advancing Arvinas’ strategy of building a global, integrated biopharmaceutical company,” said John Houston, Ph.D., Chief Executive Officer at Arvinas. “We share Pfizer’s deep commitment to people with breast cancer and are thrilled to partner with them to develop this potentially best-in-class therapy. Despite advancements in oncology in recent years, considerable unmet need persists in the treatment of HR+ breast cancer. Together with Pfizer, we will deploy our PROTAC technology in an effort to help people with this devastating disease.”
ER is the primary driver of hormone receptor (HR) positive breast cancer, which is the most common breast cancer subtype.
Endocrine therapy is a backbone of ER+ breast cancer treatment and is used as monotherapy or as combination therapy as a standard of care across treatment settings.
Arvinas and Pfizer are seeking to develop ARV-471 as the potential endocrine therapy of choice for patients and their physicians.
Interim data presented in December 2020 from the ongoing Phase 1 dose escalation clinical trial of ARV-471 in patients with locally advanced or metastatic ER+/HER2- breast cancer indicated its potential as a novel oral ER targeted therapy.
This study has enrolled heavily pretreated patients, with all patients having received prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitors.
Despite the advanced stage of disease and heavy pretreatment, these interim data, as of December 2020, demonstrated that ARV-471 can promote substantial ER degradation and exhibits an encouraging clinical efficacy and tolerability profile.
ARV-471 currently is being evaluated as a treatment for metastatic breast cancer in a Phase 1 dose escalation study, a Phase 1b combination study with Pfizer’s Ibrance (palbociclib), and a Phase 2 monotherapy dose expansion study (VERITAC).
Arvinas and Pfizer expect to initiate two additional trials of ARV-471 in 2021, including a second Phase 1b combination trial with everolimus and a trial in the neoadjuvant setting.
In 2022, Arvinas and Pfizer expect to initiate Phase 3 studies across lines of therapy in metastatic breast cancer, including combinations with Ibrance, followed by pivotal studies in the early breast cancer setting.
The two companies had previously announced in 2018 a separate research collaboration and license agreement for the discovery and development of drug candidates using Arvinas’ PROTAC technology.
Study findings that links breast cancer to everyday chemicals
In a publication review published in the Environmental Health Perspectives journal, it was found that close to 296 chemicals were responsible for the increased cause of estradiol in women. Estradiol is a form of estrogen and the major female sex hormone.
Of these chemicals, 71 caused an increase in estradiol. They included chemical flame retardants, dyes, fungicides, and pesticides.
The findings suggest that some of these synthetic chemicals could increase the risk of breast cancer by way of stimulating the two hormones linked to breast cancer: estrogen and progesterone.
Similarly, in one randomized trial, using a mixture of estrogen plus progestin which is the synthetic form of progesterone that the body produces naturally in hormone replacement therapy was shown to increase breast cancer risk.
However, scientists are still trying to establish how these chemicals are achieving this increase in estradiol.
One way, they hypothesize, is that these chemicals could be acting as aromatase, activators the opposite of drugs such as tamoxifen, and causing cells to produce more of these hormones.
The study also points out that regular exposure from multiple sources rather than one-off or rare exposures is likely to have an effect.
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