Spotlight On: Zytiga trial results and implications in prostate cancer market

Zytiga is one of three key drugs in the castrate-resistant prostate cancer (CRPC) sector. FirstWord assesses the impact of positive trial results for the Johnson & Johnson product.

What has happened?

Johnson & Johnson announced on Thursday that it has unblinded a Phase III study of Zytiga (abiraterone) in combination with prednisone for the treatment of CRPC in patients who have not received chemotherapy, based on the unanimous recommendation of the independent data monitoring committee (IDMC). The recommendation was made as part of a planned interim analysis of data, including co-primary endpoints of progression-free survival and overall survival. Based on its analysis, the IDMC recommended that patients in the placebo arm be offered treatment with Zytiga.[1]

International Strategy & Investment analyst Mark Schoenebaum suggested that the majority of analysts had anticipated this outcome, although it has come six months ahead of expectations.[2]

Zytiga in combination with prednisone is currently approved by the FDA for the treatment of CRPC in men who have received prior chemotherapy containing docetaxel. In this setting, it has demonstrated improved median survival of 4.6 months.[1]

What are the implications?

For Johnson & Johnson / Zytiga

There are approximately twice as many pre-chemotherapy CRPC patients as post-chemotherapy CRPC patients, according to analysts. Approval in this indication would therefore significantly enhance the commercial potential of Zytiga, providing access for the drug to a broader number of patients and a longer duration of treatment. A regulatory filing with the FDA is expected early in the second half of 2012. Brean Murray, Carret analyst Jonathan Aschoff noted, however, that the disclosure of full clinical data from Johnson & Johnson later in the year (anticipated at ASCO) will provide physicians with a "fully ethical reason to use Zytiga off-label in the pre-chemo setting" prior to approval.[3]

For Dendreon / Provenge

Dendreon's Provenge (sipuleucel-T) is indicated for the treatment of pre-chemotherapy CRPC asymptomatic patients. Approval of Zytiga in pre-chemotherapy patients, based on potentially strong efficacy data from the unblinded trial, would therefore provide a significant competitive threat.

Gauging the true extent of patient share that could migrate from Provenge to Zytiga remains challenging, said Schoenebaum, and is dependent on knowing what percentage of patients who receive Zytiga before Provenge will remain asymptomatic after treatment with Johnson & Johnson's drug. Predicting the percentage of patients who would fail Zytiga therapy and remain asymptomatic is very difficult at this point. Schoenebaum noted that physician feedback has been mixed with responses ranging from 0 percent to 100 percent.

Schoenebaum said that "since the trial was stopped earlier than expectations, we are operating under the assumption that the data were truly spectacular." He added that he expects Zytiga overall survival data to compare favourably to that of Provenge and believes that most patients will therefore be prescribed Zytiga ahead of Provenge in the pre-chemotherapy CRPC setting.

Dendreon confirmed on its recent fourth-quarter conference call that it had initiated trials to demonstrate the sequenced co-use of Provenge with Zytiga. Mirroring the view of Schoenebaum, however, Robert W. Baird & Co. analysts suggested that most physicians will prescribe Zytiga first in the pre-chemotherapy setting, based on the results of a survey they have carried out.[4]

Aside from efficacy considerations, there are a number of other factors that will dictate the respective usages of Zytiga and Provenge in the pre-chemotherapy CRPC setting. Provenge is an infused therapy which costs $93,000 per patient. Furthermore, a patient receives three infusions over the course of a month; therefore the cost of treatment occurs over a very short period. Rodman & Renshaw analyst Reni Benjamin told FirstWord that "doctors seem to be prescribing slowly as they get used to the billing cycle – remember, instead of paying $75,000 for a product such as Erbitux over 7-8 months, now doctors need to pay $93,000 in one month, and wait to be reimbursed."[5] With analysts suggesting that Zytiga will be priced at around $5,000 per month, an eight-month cycle would cost $40,000 by comparison. Unlike Provenge which is infused, Zytiga and Medivation's MDV3100 (see below) are also both oral treatments.

Nevertheless, Benjamin believes there is a clear place for Provenge in the treatment regimen: "While the competition may have intensified for Provenge in the chemo-naïve CRPC patients setting, we believe that if approved, [Zytiga] and MDV3100 will likely continue to be prescribed by the medical oncologist. Dendreon continues to target urologists, a strategy which, in our opinion, differentiates Provenge and ensures the longer-term growth."[6]

Schoenebaum, who forecasts 2015 sales of $660 million for Provenge, said the company will need to 'execute well' to achieve his estimate. He concedes the difficulties in forecasting market penetration rates for Provenge; however, given that it is "a unique product and precedent may not be applicable here."

For Medivation / MDV3100

Medivation is developing MDV3100, a similar product to Zytiga. Johnson & Johnson's agent has demonstrated an ability to prolong survival in post-chemotherapy CRPC patients, but has yet to receive approval for this indication. In Phase III trials, MDV3100 demonstrated a prolonged median survival of 4.8 months. Aschoff noted that MDV3100's "superiority over the Zytiga post-chemo results can be extrapolated to viewing Thursday's news as a positive for MDV3100 rather than disastrously competitive."

He added that "we expect [MDV3100's] Phase III survival result in pre-chemo patients in [the] second-half [of] 2013 to be even better than what Johnson & Johnson will show at ASCO with Zytiga, not to mention safer. The new Zytiga result also facilitates MDV3100 use off-label in the pre-chemo setting starting in [the] fourth-quarter [of] 2012." Medivation is conducting a trial in the pre-chemo indication at present.

Sources

1. Johnson & Johnson, Study Unblinded: Zytiga (abiraterone acetate) plus prednisone for asymptomatic or mildly symptomatic chemotherapy naive patients with metastatic castration resistant prostate cancer (March 8, 2012)
2. International Strategy & Investment research note (March 8, 2012)
3. Barron's "No Future" for Dendreon or Provenge (March 8, 2012)
4. Bloomberg, Johnson & Johnson Zytiga Study Sets Up Challenge to Dendreon’s Provenge (March 8, 2012)
5. Reni Benjamin, Rodman & Renshaw, Interview (February 28, 2012)
6. Rodman & Renshaw research note (March 8, 2012)

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