Last updated: January 1, 2025
Introduction to ARV-471
ARV-471 is an investigational oral PROTAC® (PROteolysis TArgeting Chimera) estrogen receptor protein degrader, co-developed by Arvinas, Inc. and Pfizer Inc. This drug candidate is designed to treat patients with locally advanced or metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer.
Collaboration and Financial Terms
In July 2021, Arvinas and Pfizer announced a global collaboration to develop and commercialize ARV-471. Under this agreement, Pfizer paid Arvinas $650 million upfront and made a $350 million equity investment in Arvinas, acquiring approximately 3.5 million newly issued shares of Arvinas common stock. The companies will equally share worldwide development costs, commercialization expenses, and profits. Arvinas is also eligible to receive up to $400 million in approval milestones and up to $1 billion in commercial milestones[1].
Clinical Development Status
Phase 1 and Phase 2 Trials
ARV-471 is currently being evaluated in several clinical trials. It has completed Phase 1 dose escalation studies and is ongoing in a Phase 1b combination study with Pfizer’s IBRANCE® (palbociclib) and a Phase 2 monotherapy dose expansion study (VERITAC). The VERITAC trial has shown promising results, with a clinical benefit rate (CBR) of 38% in evaluable patients, defined as confirmed complete response, partial response, or stable disease for at least 24 weeks. The drug has also demonstrated a favorable tolerability profile, with most treatment-related adverse events reported as Grade 1 or 2[2][4][5].
Key Findings from VERITAC Trial
- Clinical Benefit Rate: ARV-471 achieved a CBR of 38% in the VERITAC trial, with 37.1% and 39% CBR in the 200 mg and 500 mg treatment arms, respectively.
- Progression-Free Survival: The median progression-free survival (PFS) was 3.7 months in all patients and 5.7 months in patients with ESR1 mutant tumors.
- Tolerability: The drug showed a favorable tolerability profile, with the majority of treatment-related adverse events being Grade 1 or 2[2][4][5].
Future Clinical Milestones
Phase 3 Trials
Based on the positive results from the Phase 2 trials, Arvinas and Pfizer plan to initiate two Phase 3 registrational trials. One trial will evaluate ARV-471 as a second-line treatment in patients with ER+/HER2- metastatic breast cancer, and the other will assess ARV-471 in combination with palbociclib as a first-line treatment. These trials are expected to start in the fourth quarter of 2022 and will be pivotal for the drug’s regulatory approval and commercialization[5].
Market Projection
Unmet Need in Breast Cancer Treatment
Despite advancements in oncology, there remains a significant unmet need in the treatment of ER+/HER2- breast cancer. Current treatments, such as fulvestrant, have limitations, and there is a need for more effective and tolerable therapies. ARV-471, with its novel PROTAC technology, has the potential to address this gap by offering a more targeted and efficient way to degrade the estrogen receptor, a key driver in ER+ breast cancers[1][3].
Competitive Landscape
ARV-471 is positioned to compete with existing therapies like fulvestrant. However, the drug's clinical profile, particularly its ability to show superior anti-tumor activity in preclinical studies and its favorable tolerability, suggests it could become a preferred treatment option. The differentiation in efficacy, especially in patients with ESR1 mutant tumors, could further enhance its market potential[3][4].
Analysts’ Perspectives
While some analysts have expressed mixed views on the drug's clinical benefit rates, particularly the variability in efficacy between ESR1 mutant and wild-type patients, the overall consensus is that ARV-471 has the potential to become a significant player in the breast cancer treatment market. The initiation of Phase 3 trials is seen as a positive step towards validating its clinical benefit and commercial viability[4].
Key Takeaways
- Collaboration and Funding: Arvinas and Pfizer have a robust collaboration with significant financial commitments, ensuring the drug’s development and commercialization.
- Clinical Efficacy: ARV-471 has shown promising clinical benefit rates and a favorable tolerability profile in Phase 2 trials.
- Future Trials: Phase 3 trials are planned to start in late 2022, which will be crucial for regulatory approval and market entry.
- Market Potential: The drug addresses a significant unmet need in ER+/HER2- breast cancer treatment and has the potential to become a new standard of care.
FAQs
What is ARV-471 and how does it work?
ARV-471 is an investigational oral PROTAC® estrogen receptor protein degrader designed to specifically target and degrade the estrogen receptor (ER) in tumor cells, thereby inhibiting the growth of ER-positive breast cancer.
What is the current clinical status of ARV-471?
ARV-471 is currently in Phase 2 clinical trials, with positive results from the VERITAC trial showing a clinical benefit rate of 38% and a favorable tolerability profile. Phase 3 trials are planned to start in late 2022.
What is the significance of the collaboration between Arvinas and Pfizer?
The collaboration combines Arvinas’ expertise in targeted protein degradation with Pfizer’s global capabilities and deep expertise in breast cancer, enhancing the development and potential commercialization of ARV-471.
How does ARV-471 compare to existing treatments like fulvestrant?
ARV-471 has shown superior anti-tumor activity compared to fulvestrant in preclinical studies and has a favorable tolerability profile, suggesting it could become a preferred treatment option for ER+/HER2- breast cancer.
What are the next steps in the development of ARV-471?
Arvinas and Pfizer plan to initiate two Phase 3 registrational trials in late 2022, one as a second-line treatment and the other in combination with palbociclib as a first-line treatment.
Sources
- Arvinas and Pfizer Announce Global Collaboration to Develop and Commercialize PROTAC® Protein Degrader ARV-471. Pfizer. Retrieved November 22, 2022.
- Arvinas Announces ARV-471 Achieves a Clinical Benefit Rate of 38% in Evaluable Patients and Continues to Show a Favorable Tolerability Profile in its Phase 2 Expansion Trial (VERITAC). Arvinas. Retrieved November 22, 2022.
- Arvinas and Pfizer Announce PROTAC® Protein Degrader ARV-471. Pfizer. Retrieved December 10, 2021.
- Arvinas' Experimental Breast Cancer Drug Fails to Impress Analysts. BioSpace. Retrieved November 23, 2022.
- Arvinas Announces ARV-471 Achieves a Clinical Benefit Rate of 38 Percent in Evaluable Patients and Continues to Show a Favorable Tolerability Profile in its Phase 2 Expansion Trial (VERITAC). BioSpace. Retrieved November 22, 2022.
