Xtandi – Replacing competitor from Zytiga to Casodex (Bicalutamide) for a bigger pie in Prostate cancer & Finding its niche in crowded BC market
Xtandi + Zytiga vs. ARN-509 + Zytiga – Who will win the race?
Rising star Anti Androgens – Third generation Antiandrogens- What left for AR-V7 mutants after TOK-001 failure?
Late Stage Prostate Cancer Pipeline drugs – AKT inhibitors or PARP inhibitors or a new MoA combination with Antiandrogen or IO combo – Competing to Xtandi/Zytiga or targeting Xtandi/Zytiga Resistance Population?
Increase in prevalence of Prostate cancer and availability of new treatment options (Zytiga, Xtandi, Cabazitaxel, and Xofigo) in last few years has extended role of newer oral Antiandrogens to treat metastatic CRPC patient populations where the unmet need was high. This has expanded the WW market size of Prostate cancer drugs to $7b in 2016 from $2.5b in 2011. Now nmCRPC, HSPC, and Xtandi/Zytiga resistance population are the markets wherein new pipeline drugs are under development.
Reported PhII clinical data of Xtandi, ARN-509 and ODM-201 in nmCRPC when indirectly compared demonstrate the bar is high for ARN-509 to compete against Xtandi in the nmCRPC market and while ODM-201 is few years behind in clinical development. While in mHSPC reported clinical results of STAMPEDE study opens the door for docetaxel combination approach as a standard of care in the first-line setting.
Around 8 plus drugs are in PhIII development for Prostate cancer treatment and 26 plus drugs are in PhII development (21 small molecules) – success of a few (ARN-509, ODM-201, AZD 5363, GX301) in coming years will expand nmCRPC ($3.5be), mHSPC market ($1be) and Xtandi/Zytiga resistant population ($1be) market by 2023. Longer duration of therapy and high prevalence makes the earlier setting market more attractive and bigger for newer options than the late stage if they succeed.
For drugs targeting through androgen pathway – Now trials and clinical development is underway for second and third generation androgen receptor inhibitors (ARN-509, ODM-201, ODM-204, EPI-506, VT-464, TAS-3681, and DR103). While androgen synthesis inhibitors still need a proof of concept in the clinic due to the failure of TAK-700 & TOK-001. Expected data from VT-464 (Apr 2017) & ASN-001 will be important to watch to taste the success for this class. Androgen receptor degrader is another MoA in development from a decade and success of in-clinic compound GTX-758 (Data expected anytime from now as study completed in March 2016- less likely to succeed) will decide the proof of concept.
Other than pipeline drugs targeting androgen pathway, NCE targeting AKT pathway (AZD5363, Ipatasertib) appears to be more promising to succeed in late stage, while drugs acting through PARP inhibition (Olaparib, Niraparib) still needs a taste of success. Another interesting pipeline asset is an LHRH agonist LMIS 50 mg, which is designed to overcome the drawbacks of the commercial depot products containing GnRH agonists by using a proprietary delivery system.
Also, 6 therapeutic vaccines are in clinical development to treat prostate cancer. Recently launched PD-L1 IO therapy has increased hope of treating cancer in a much safer way. Current ongoing studies of late-stage IO mab are in Ph I/II clinical development and would be able to answer of PTEN hypothesis for the role of PD-1, PD-L1 inhibitor to treat prostate cancer in coming years.
Resistant development is another challenge with the long-term use of Xtandi/Zytiga and needs to be addressed by pipeline second/third generation Antiandrogens/ combination approach with IO/PARP/AKT inhibitors to treat mCRPC. Increase in pricing pressure in the developed market again put inference on Combination approach unless the advantage is significant and improve the Q0L in the earlier setting. Due to that, drugs targeting adjuvant setting has a high bar to deliver (Atezolizumab, GX301, Mipsagargin, and Olaparib) in the clinical development to add significant value.
This report details current unmet need, changing regulatory requirement, reimbursement challenges & market dynamics of Prostate Cancer drugs. Report mention pipeline Antiandrogens, late-stage prostate cancer pipeline drugs/new Mechanism of action & major companies developing Prostate cancer drugs. It also provides insight into the clinical development strategy of combination pipeline/marketed drugs & therapeutic competitive landscape to find treatment paradigm fit & market potential of new drugs for the treatment of Prostate Cancer