Strong performance for Medivation Inc.’s late-stage prostate cancer drug MDV3100 on all secondary efficacy endpoints in the Phase III AFFIRM trial, with adverse event rates about on par with placebo, complement a previously announced 4.8 month improvement in overall survival in the study.

The AFFIRM results released at the American Society of Clinical Oncology Genitourinary Cancers Symposium provide a much more complete picture than what has been available until now, showing side effect rates about the same as placebo.

An androgen receptor signaling inhibitor, MDV3100 is partnered with Astellas Pharma Inc.The companies are planning a pre-NDA meeting with FDA “early in 2012” to determine a path for filing in castrate-resistant prostate cancer following failure with chemotherapy.

The pivotal AFFIRM study tested MDV3100 in 1,199 post-chemo, progressive CRPC patients randomized 2:1 to the treatment drug or placebo.

Details about performance in secondary efficacy endpoints, such as time to progression of disease and safety, were presented during a Jan. 31 press teleconference. The data were presented and further analyzed at the symposium itself on Feb. 2.

The data help to shed further light on the drug’s profile in a competitive market, following an announcement in November that the candidate had demonstrated a 4.8 month OS survival benefit, equivalent to a 37% reduction in risk, results so positive that the trial was discontinued Also see "Medivation Aims To Capture Prostate Cancer Market, One Trial At A Time" - Pink Sheet, 14 November, 2011..

This efficacy did not, it appears, come at the price of safety. In the AFFIRM study, the overall adverse event rate for the test drug was 98.1% vs. 97.7% for placebo, while the rate of serious side effects was 33.5% for those on treatment vs. 38.6% for placebo (see table).

Total Events

≥ Grade 3 events

MDV3100

(n=800)

Placebo

(n=399)

MDV3100

(n=800)

Placebo

(n=399)

Adverse Events

98.1%

97.7%

45.3%

53.1%

Serious Adverse Events

33.5%

38.6%

28.4%

33.6%

Discontinuations due to Adverse Events

7.6%

9.8%

4.6%

7.0%

Adverse events leading to deaths

2.9%

3.5%

2.9%

3.5%

Source: H. Scher, Memorial Sloan-Kettering Cancer Center, Presented at ASCO Genitourinary Cancers Symposium 2012

“The benefit-to-risk profile will likely position it as the first agent after docetaxel therapy,” Howard Scher, the trial’s co-principal investigator and chief of genitourinary oncology at Memorial Sloan-Kettering Cancer Center, said during the press briefing.

MDV3100 is one of many new contenders in prostate cancer. The market for prostate cancer therapies is now booming, with three new treatments approved in the last few years for different segments of the population – all showing a survival benefit Also see "Prostate Cancer Market Snapshot: More Than Provenge" - Pink Sheet, 22 November, 2010.. Johnson & Johnson’s Zytiga (abiraterone), approved in April 2011 for post-chemo use, has had a strong launch, including off-label penetration into chemo-naïve patients Also see "J&J’s Zytiga –The Anatomy Of A Cancer Launch" - In Vivo, 30 November, 2011.. The Street has viewed MDV3100 as a potentially strong rival because – unlike Zytiga – MDV3100 does not have to be administered with prednisone. Sanofi’s Jevtana (cabazitaxel) was cleared by FDA in June 2010 for use after chemotherapy, but while this drug showed a 2.4 month improvement in OS it also has been associated with significant side effects.

In the AFFIRM study of MDV3100, there was significant use of both Zytiga and Taxotere following progression – 58.4% for the placebo group vs. 41% for MDV3100. The most common follow-up therapy was Zytiga, used by 24.3% of placebo patients and 20.9% on the test drug.

“In spite of that, MDV3100 was able to demonstrate significant benefit over the placebo arm,” Medivation CEO David Hung said in an interview.

The total length of survival was 18.4 months for the test drug vs. 13.6 months for placebo.

Progression On Hold

On average, based on PSA tests, those on MDV3100 had 8.3 months of progression-free survival vs. three months for placebo.

For the treatment group, 54% had a 50% or greater decline, compared to 1.5% for placebo. And furthermore, 24.8% had a 90% PSA decline or more, vs. 9% for placebo.

This impact on PSA is “unprecedented and will definitely change the way we take care of patients in the office,” said the ASCO GU press conference moderator, Nicholas Vogelzang, head of the genitourinary cancer section at the Nevada Cancer Institute.

This impact was also demonstrated on imaging studies – median radiographic progression-free survival was 8.3 months vs. 2.9 months for placebo.

Looking ahead, Astellas and Medivation have a broad Phase III development program for MDV3100, with trials ongoing in chemo-naïve patients, among other populations. The companies have not disclosed release dates for data from the other studies.

Phase III Data AFFIRM Safety As Well As Survival For MDV3100

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