Johnson & Johnson could be planning to use new data on Procrit (epoetin alfa) to defend its market position for treatment of anemia related to chronic kidney disease in patients who are not on dialysis.

Both J&J and Amgen - the marketer of Epogen (epoetin alfa) and Aranesp (darbepoetin alfa) -could be facing competition from Roche next year if its investigational continuous erythropoietin receptor activator Mircera , with a clear dosing advantage over short-acting epoetin, is approved by FDA.

J&J and Roche both presented data Nov. 20 on the dosing of their respective therapies at the American Society of Nephrology annual meeting in San Diego.

J&J presented data for the first time on the treatment of anemia-related CKD with Procrit once every two weeks; the FDA-approved initiation dose of Procrit for this patient population is 50-100 units/kg three times per week.

In the single-arm study of 67 patients with CKD not on dialysis, 88% of patients treated with Procrit 20,000 units once every two weeks achieved a target hemoglobin of between 11 and 12 g/dL. The mean Hb reached the target range at week six and stayed in that range for the remainder of the 28-week study.

The results suggest that patients could be treated with Procrit less frequently, according to J&J. That data could be beneficial if Roche's Mircera were to reach the market. Roche already released initial data from its Phase III program for Mircera in July showing a dosing advantage over epoetin alfa (¹ Also see "Roche’s Renal Anemia Studies Show Benefits Of CERA Once-Monthly Dosing" - Pink Sheet, 17 July, 2006.).

The company released additional Phase III data at the nephrology meeting, including two studies, ARCTOS and AMICUS, showing that Mircera administered once every two weeks corrected untreated renal anemia in patients with CKD, both on dialysis and not on dialysis. Two other studies, PROTOS and MAXIMA, found that Mircera maintained stable hemoglobin levels once every two or four weeks in dialysis patients who had previously been taking short-acting epoetin dosed one to three times per week.

The PROTOS (Patients Receiving CERA Once a Month for the MainTenance of Stable Hemoglobin) and MAXIMA (Maintenance of Hemoglobin Excels with IV Administration of CERA) studies were designed to show non-inferiority of Mircera on the Hb concentration in dialysis patients converted from more frequent dosing with epoetin alfa/beta to Mircera dosed once every two weeks or once every four weeks.

The primary endpoint was mean change in Hb between baseline and the evaluation period. PROTOS showed Mircera subcutaneous injection was able to maintain stable Hb levels in patients converted from SC epoetin alfa or beta up to three times a week.

For patients receiving Mircera every two weeks, the mean difference in Hb from baseline was 0.52 g/dL in the evaluation period and 0.68 g/dL for the follow up period. For those patients treated every four weeks, the mean difference in Hb levels were 0.57 g/dL for the evaluation period and 0.76 g/dL during the follow up period. The mean difference in Hb from baseline for the epoetin-treated arm was 0.57 g/dL for the evaluation period and 0.68 g/dL for the follow up.

A subgroup analysis found that Mircera's effect on Hb levels was not impacted by patients' age, gender or diabetic status.

MAXIMA evaluated the efficacy of intravenous Mircera in maintaining stable Hb levels in patients converted from epoetin alfa or beta, with similar non-inferiority results.

Roche's Phase III program represents the largest initial registration program ever conducted for the treatment of renal anemia, including two initiation/correction and four conversion/maintenance studies.

The competitive hostility between Roche and Amgen has been growing. Amgen's Epogen and Aranesp are protected by dozens of patents and the company has filed a patent infringement suit against Roche, attempting to block the launch of Mircera in the case it is approved by FDA; Roche's BLA for Mircera is pending at FDA with a February user fee date (² Also see "Roche Continuous Epoetin CERA BLA Submitted For Dosing Every Four Weeks" - Pink Sheet, 20 April, 2006.).

Roche, however, maintains that Mircera is a new chemical entity, different from recombinant human EPO in chemical and biological activity. In addition, Roche has filed counterclaims against Amgen, alleging that Amgen is participating in a broad anticompetitive scheme against Roche (³ Also see "Amgen’s “Anticompetitive Scheme” On EPO Should Be Invalidated By Court, Roche Says" - Pink Sheet, 7 November, 2006.).

Two studies published in The New England Journal of Medicine Nov. 16 may also have an impact on the category. The studies, sponsored by J&J (CHOIR) and Roche (CREATE) found that achieving higher hemoglobin levels in CKD patients does not have a positive effect on cardiovascular outcomes and could even have a negative impact (⁴ Also see "Epoetin Alfa Increases Cardiovascular Risks When Targeting High Hemoglobin Levels, J&J Study Finds" - Pink Sheet, 16 November, 2006.).

The study authors concluded that the trials confirmed the current best practice guidelines, recommending partial correction of anemia and not normalization of hemoglobin levels in CKD patients. Based on the findings, however, the authors recommend a target hemoglobin level of 11-12 g/dL to correct anemia in CKD patients compared to recently expanded Kidney Disease Outcomes Quality Initiative guidelines that set a target range of 11-13 g/dL.

-Jessica Merrill (j.merrill@elsevier.com)

J&amp;J, Roche Data Show Dosing Benefit In Treating Anemia With Procrit, Mircera

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J&J, Roche Data Show Dosing Benefit In Treating Anemia With Procrit, Mircera