Niraparib + abiraterone acetate

This is the first and only dual action (or fixed-dose combination [FDC]) tablet combining a PARP inhibitor (niraparib) and a next-generation hormonal therapy (abiraterone acetate). Its ability to serve as a treatment for patients with deleterious or suspected deleterious BRCA-mutated, metastatic castration-resistant prostate cancer (mCRPC), should help to fulfill the need for more effective treatments. BRCA-positive mCPRC disease tends to be more aggressive; ~10-15% of patients with mCRPC harbor BRCA gene mutations. The approvals in both the United States and European Union represent the third prostate cancer treatment by Johnson & Johnson Innovative Medicine to reach this milestone and highlight the importance of reliable predictive biomarkers for precision treatment of patients. In August 2023, Foundation Medicine Inc received approval from the U.S. FDA for FoundationOne®CDx to be used as a companion diagnostic for niraparib + abiraterone acetate.

niraparib + abiraterone acetate

  1. Johnson & Johnson Innovative Medicine
  2. PARP inhibitor and hormone therapy
  3. Once daily oral administration in combination with prednisone or prednisolone to treat BRCA-positive mCRPC
  4. Also being evaluated for metastatic, hormone-sensitive prostate cancer (mHSPC) with HRR gene mutations
  5. ~76K new cases of previously untreated mCRPC
  6. ~110K new cases of rmHSPC in the G7 markets in 2023

Why is it a drug to watch?

The development of niraparib + abiraterone acetate used an inventive and smart life cycle management strategy (especially considering generics are available for abiraterone). It has a competitive edge given the very good efficacy as well as the positive physician opinion and desire to prescribe it. As an FDC in a single tablet, it is a convenient alternative.

U.S. FDA and EMA approvals were based on the results of a large phase 3 clinical trial (MAGNITUDE) conducted with patients with mCRPC (with or without homologous recombination repair [HRR]-associated gene alterations) who received niraparib + abiraterone acetate plus prednisone, whose outcomes were compared with those of patients who received placebo + abiraterone plus prednisone. The findings included the following:

  1. Median radiographic progression free survival (rPFS) in the BRCA1/2 subgroup of 19.5 months (vs 10.9 months with placebo + abiraterone)
  2. Median rPFS in the full HRR+ cohort of 16.7 months (vs 13.7 months with placebo + abiraterone)
  3. Manageable safety profile, with no new safety signals that affected the benefit-risk profile

Review and
approval status

April 2022

  • MAA filed: EMA

February 2023

  • NDA filed: U.S. FDA

April 2023

For patients with BRCA-positive mCRPC, to be used in combination with prednisone

  • Approved: EMA

August 2023

For patients with deleterious or suspected deleterious BRCA-positive mCRPC, as detected by an FDA-approved test

  • Approved: U.S. FDA

Actual and expected launch:

  • 2023: European Union, United States

How will niraparib + abiraterone acetate impact the market for prostate cancer?

  1. Hormonal therapy is the cornerstone of drug treatment in all patient populations and will remain the dominant drug class, including novel hormonal therapies (e.g., abiraterone, enzalutamide) expecting to hold approximately 50% of the total prostate cancer market by 2032.
  2. However, treatment is becoming increasingly diversified with the approval of novel targeted agents such as PARP inhibitors and prostate-specific membrane antigen (PSMA)-targeted radioligands.
  3. The late-phase pipeline spans a wide range of drug classes and novel therapies (e.g., PARP inhibitors, kinase inhibitors, PSMA-targeted radioligands, angiogenesis inhibitors).
  4. Niraparib + abiraterone acetate will be the sales-leading emerging agent, earning major-market sales of $2.9 billion in 2032. Due to long treatment durations and the premium price of niraparib + abiraterone acetate, 75% of those sales will come from the mHSPC setting.
  5. Although other PARP inhibitor + hormonal therapy combinations (e.g., Lynparza + abiraterone from AstraZeneca and MSD) are available, they are “open” combinations (i.e., two drugs administered as separate tablets with different dosing schedules).

What gaps in treatment does niraparib + abiraterone acetate fill?

When treated with current standard of care, mCRPC remains an incurable disease, and patients with BRCA-positive mCRPC are more likely to have aggressive disease, experience poor outcomes and have shorter survival times. Drugs with novel MOAs are needed to provide more effective treatment options. PARP inhibitors have the potential to partially satisfy this unmet need, and targeted therapies with predictive biomarkers will help ensure that patients are matched to the most effective MOA. Compared with earlier-to-market PARP + hormonal agent combinations for this molecularly defined subset of patients, niraparib + abiraterone acetate provides a convenient dosing schedule (once-daily dose).

What hurdles might it need to overcome to reach blockbuster status?

Niraparib + abiraterone acetate is likely to face stiff competition from other PARP inhibitor and hormone therapy combinations. Lynparza in combination with abiraterone acetate has the first-to-market advantage in the first line mCRPC with BRCA mutation segment. Lynparza also has greater physician familiarity due to its earlier approval as monotherapy in later-line settings. Another competitor, TALZENNA® (Pfizer Inc) in combination with XTANDI® (Pfizer Inc and Astellas Pharma Inc), has a broader label that also extends to patients with other HRR mutations. Additionally, some oncologists will prefer the dosing flexibility and cost saving offered by “open combinations” over FDCs.

expected sales in 2029
probability of success for niraparib + abiraterone acetate in the U.S.
Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of November 3, 2023

Drug Timeline &
Success Rates

– Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of November 3, 2023

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