Amgen and Praecis are requesting a meeting with FDA to discuss issues surrounding the NDA for their prostate cancer treatment Plenaxis (abarelix).

Plenaxis received a "not approvable" letter June 11. The NDA for the gonadotropin-releasing hormone antagonist was submitted Dec. 12, 2000, and was under a priority review with a user fee date of June 12.

Amgen and Praecis suggested as recently as June 4 that the application was on track. A release described Phase III studies on prostate specific antigen and testosterone reduction and noted the product's priority review status.

FDA's action letter was the first communication regarding the application the companies had with the agency since submitting the NDA, Praecis said. However, the companies have received two citations for pre-approval promotion from the agency's ad division.

A press release announcing the Amgen/Praecis collaboration drew a letter from FDA objecting to statements that abarelix acts faster than other products (¹ [A#00610230022]).

A letter in March from FDA cited an unbranded ad in the Journal of Urology. The ad states "Surge and flare: Is there really a difference?" The ad suggests that Plenaxis will be superior to and safer than luteinizing hormone-releasing hormone antagonists, FDA said (² Also see "Formulary-Tailored Pharmacoeconomic Models Being Used By Rx Sales Reps" - Pink Sheet, 2 April, 2001.).

The companies maintain that abarelix yields a faster suppression of testosterone without the initial surge associated with other prostate cancer treatments. In a 271-patient trial versus TAP's Lupron (leuprolide), no abarelix patients "experienced a surge of testosterone, compared with 82% of the leuprolide-acetate patients," a press release states.

Another Phase III trial compared abarelix to leuprolide plus bicalutamide (AstraZeneca's Casodex), a combination that is used to mitigate testosterone surge.

Plenaxis, "a new depot GnRH antagonist, is devoid of this initial surge and, therefore could potentially eliminate the cost, noncompliance, and inconvenience associated with combination therapies," a study abstract maintains.

The 255-patient study demonstrated that 100% of the abarelix patients versus 14% of the active control group avoided testosterone surge.

Abarelix appeared to be equally as effective as control in reducing PSA in patients. At 24 weeks, 100% of each group met the endpoint of a 50% reduction from baseline in serum PSA levels.

The abarelix versus Lupron trial showed a faster initial PSA decline for abarelix but equivalent levels for both therapies after several weeks.

Abarelix patients had a 50% PSA reduction at week two versus a 15% reduction for the 91 leuprolide patients. After four weeks, abarelix showed a 75% reduction compared to 61% for leuprolide. At day 85, both products showed greater than 90% reduction in serum PSA levels.

The clinical significance of testosterone surge has been questioned by clinicians. Following the presentation of abarelix Phase II data at the American Society for Clinical Oncology 2000 annual meeting, physicians discussed whether the surge findings translated into a survival advantage or disadvantage (³ Also see "Praecis/Amgen Abarelix-Depot Spares Patients Initial Testosterone Surge" - Pink Sheet, 29 May, 2000.).

For the second endpoint of rapidity of medical castration in the abarelix v. Lupron/Casodex trial, "a significantly greater number of [abarelix] (68%) versus [combination-therapy] (0%) patients achieved castration on day 8." Both therapies had similar rates of allergic events requiring medical intervention.

Amgen and Praecis are currently conducting Phase II trials of abarelix for endometriosis.

Amgen has a number of applications for significant products that have been pending at FDA for over a year. FDA's arthritis advisory committee is expected to review Amgen's rheumatoid arthritis treatment anakinra in August (⁴ Also see "Amgen Anakinra Arthritis Advisory Committee Review Expected In August" - Pink Sheet, 30 April, 2001.). The BLA was filed in December 1999.

A BLA for Amgen's Epogen successor product Aranesp was also submitted in December 1999. Amgen is still discussing labeling with FDA. The product recently received approval in Europe for anemia related to chronic kidney failure (⁵ Also see "Amgen Aranesp European Approval For Dialysis Use Permits Bi-Weekly Dosing" - Pink Sheet, 18 June, 2001.).

Amgen/Praecis Ask For FDA Meeting After Plenaxis Deemed "Not Approvable"

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