Mikael Dolsten, M.D., Ph.D.
Chief Scientific Officer and President, Worldwide Research, Development and Medical at Pfizer
Thank you, Dave.
Today, I'd like to start off with one of the four pillars of our oncology portfolio, which are breast, urogenital, blood cancers and precision medicine. Within urogenital, prostate cancer is an area in which we have strong momentum. Recent positive study results further strengthen our franchise, building upon the global standard of care set by XTANDI, and underscoring our long-standing commitment to the pursuit of breakthroughs that define new standards of care in prostate cancer.
I'll highlight data from two Phase 3 studies: EMBARK and TALAPRO-2, as well as early, but promising signals from our EZH2 inhibitor, each of which has the potential to reach broader patient populations across the treatment continuum in prostate cancer. Final analysis from TALAPRO-2, evaluating our potential blockbuster PARP inhibitor TALZENNA in combination with XTANDI were presented at ASCO GU. Results showed significant and clinically meaningful improvement across the all-comers population in radiographic progression-free survival, or rPFS, in men with metastatic castration-resistant prostate cancer, with or without homologous recombination repair or HRR gene mutations.
There was a 37% reduction in risk of disease progression. Median rPFS in patients treated with TALZENNA and XTANDI was not reached at the time of analysis versus 21.9 months for placebo plus XTANDI. A trend in overall survival favoring TALZENNA plus XTANDI was also observed, though these data are immature. The final OS data will be reported once the predefined number of survival events has been reached.
Treatment with TALZENNA and XTANDI resulted in statistically significant improvement in overall response rates, which suggest a potential cooperative effect between the two treatments. The U.S. FDA has granted Priority Review for our sNDA for TALZENNA in combo with XTANDI for metastatic castration-resistant prostate cancer, with a decision expected in '23. The ongoing TALAPRO-3 study, if successful, may further expand the reach of this potential blockbuster into the HRR-deficient metastatic castration-sensitive population.
We recently presented data from our Phase 3 EMBARK study evaluating XTANDI plus leuprolide in men with non-metastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence at the American Urological Association's '23 Annual Meeting. The study met its primary endpoint with statistically significant and clinically meaningful improvement in metastasis-free survival, with a 58% reduction in risk for radiographic progression or death. Key secondary endpoints were met including time to PSA progression.
These results suggest XTANDI, the only novel hormone therapy approved for three disease states of prostate cancer in the U.S. has the potential if approved to expand to patients in the hormone-sensitive, or castration-sensitive setting, for the first time.
Next, I'd like to share early data from one of our next-wave candidates, a potential first-in-class and best-in-class EZH2 inhibitor, which we shorthand as 1497. EZH2 is an epigenetic transcriptional repressor that is frequently overexpressed in prostate cancer. We believe that inhibition of EZH2 may provide synergistic effects in combination with XTANDI, with the potential to address unmet needs of patients with androgen-sensitive and resistant disease.
Here are data from our ongoing Phase 1/2 study evaluating 1497 in second-line mCRPC patients with prior abiraterone and/or XTANDI, and up to one line of chemo. On the left are updated data from a Phase 1 dose escalation study shared at ESMO last year. These encouraging results show durable anti-tumor activity in both XTANDI-naive and -experienced patients, with all XTANDI-naive patients having received prior abiraterone. Importantly, this suggests that the addition of our EZH2 inhibitor has the potential to sensitize XTANDI-resistant tumors, which is an increasing clinical unmet need.
The early rPFS data are also highly encouraging, reaching 8.7 months in the XTANDI-experienced and 17.1 months in XTANDI-naive, both of which are notably longer than historical controls. For example, in the control arm of the CARD study, rPFS for XTANDI alone was only 4.8 months in XTANDI-naive patients.
And although cross-trial comparisons cannot be made, these results, in combination with the emerging objective response rate and PSA50 response, are supportive of the contribution of our EZH2 inhibitor candidate in driving these responses. From a safety perspective, the combination was generally well tolerated, with mostly Grade 1 and Grade 2 events. The randomized Phase 2 study in second-line mCRPC is ongoing, with data expected in early '24.
Now, we turn to the potential for near-term growth across our respiratory vaccine franchise. Prevnar 20 or our 20-valent pneumococcal conjugate vaccine, is now approved for children aged six weeks through 17 years. We are confident in our ability to maintain leadership in the pneumococcal vaccine space with Prevnar 20, which offers the broadest serotype coverage of any pediatric pneumococcal conjugate vaccine, helping to protect against the 20 serotypes in the vaccine.
We have strong momentum with our RSV vaccine candidate, having received a positive VRBPAC [Phonetic] Committee vote supporting potential approval to help combat RSV in older adults and PDUFA dates for our older adults and maternal indications in quick succession in the coming months. And just last month, the New England Journal of Medicine published results from the two positive Phase 3 studies. Emerging data from the middle of the second RSV season in the Northern Hemisphere in the Phase 3 older adult study support meaningful durable vaccine efficacy; we will share the data once complete.
In the coming months, we plan to start a Phase 3 study of the RSV vaccine candidate in 18-year-olds to 60-year-olds at high risk for RSV and in immunocompromised adults 18 and over, and a Phase 1 study in two-year-olds to 18-year-olds at high risk, with the potential to expand broadly the reach of our vaccine candidate both to those aged 18 to 60 with high-risk conditions as well as to pediatrics and adolescents.
Our RSV-Flu coadministration study met its primary endpoint, demonstrating non-inferiority for all four flu strains and the RSV A and B strains. This suggests the RSV vaccine candidate, if approved, could be co-administered with flu vaccinations and add an important component of seasonal protection against respiratory pathogens.
Finally, the FDA recently updated the EUA for our Omicron BA.4/BA.5 [Phonetic] bivalent COVID-19 vaccine to enable those at high-risk of severe COVID-19 illness, including the elderly and immunocompromised, to partner with their healthcare providers to be proactive and in helping them to protect themselves against COVID-19. We anticipate another update from FDA in June that will provide guidance on COVID-19 vaccine strains and vaccination timing for the 2023 fall and winter seasons.
Beyond vaccines, antivirals are an important component of our strategy in respiratory viruses. Here we share data for the first time from our second-generation oral COVID-19 antiviral candidate, a potent and selective SARS-CoV-2 Mpro inhibitor that is currently in Phase 1.
We designed this candidate to achieve clinical exposure that would have similar anti-viral activity to PAXLOVID but without the need for ritonavir boosting and with the potential for reduced drug interactions. Early results from Phase 1 dose escalation are encouraging, with no dose-limiting safety or tolerability findings. Dosing achieved concentrations many-fold over in vitro EC90 and is therefore expected to have similar antiviral activity to PAXLOVID.
On the right are preliminary results from a Phase 1 pharmacokinetic study of midazolam drug interaction, which is a well-known standard for indicating CYP3A4-mediated drug-drug interactions. These data show there is a lack of such drug-drug interactions, suggesting there may be no related restrictions of co-dosing with drugs metabolized by CYP enzymes.
Based on these encouraging data, we are planning to advance to a Phase 2 dose-ranging study in the first half of this year. In addition to the assets I spoke about today, we continue to make progress on the pipeline with more than 25 milestones recently achieved or anticipated through the first half of '24.
As an example: in inflammation & immunology, the FDA has approved our sNDA for CIBINQO, enabling a label expansion for adolescents with moderate-to-severe dermatitis. In internal medicine, ZAVZPRET, the migraine nasal spray has received FDA approval, expanding our migraine portfolio. Recently, the FDA Advisory Committee voted in support of PAXLOVID's favorable benefit-risk profile, with a soon PDUFA date in May.
In closing, we are very excited about the potentially transformative catalysts expressed across the pipeline as we work with continued urgency to bring breakthroughs to patients.
Thank you. Let me turn it over to Chris to start Q&A.
