Ac­cord­ing to reg­u­lar up­dates from Am­gen over the past two years, in­ves­ti­ga­tors marched through a trio of late-stage stud­ies for etel­cal­ce­tide (AMG416) with noth­ing but good things to re­port. The drug scored out­stand­ing da­ta for sec­ondary hy­per­parathy­roidism (SH­PT), a dis­ease that af­fects chron­ic kid­ney dis­ease pa­tients on he­modi­a­lyis.

And this evening Am­gen re­port­ed that the drug was re­ject­ed by the FDA. The news came in a terse state­ment, with­out a hint about what the agency ob­ject­ed to.

The com­mer­cial name for this drug is Parsabiv. And here’s what Am­gen — a big biotech not known for ex­plain­ing dis­taste­ful things — had to say about it:

Am­gen is re­view­ing the Com­plete Re­sponse Let­ter, and we an­tic­i­pate a post-ac­tion meet­ing with the FDA lat­er this year to dis­cuss the Com­plete Re­sponse. The Com­plete Re­sponse Let­ter does not im­pact our reg­u­la­to­ry sub­mis­sions in oth­er re­gions.

Am­gen test­ed the drug in more than a thou­sand pa­tients, re­port­ed­ly meet­ing its pri­ma­ry end­points by slash­ing dan­ger­ous­ly high parathy­roid hor­mone lev­els. In one study 74.7% of sub­jects on the drug hit its tar­get, com­pared to just 8.9% in the place­bo arm. In an­oth­er Phase III tri­al the new drug out­per­formed Am­gen’s block­buster drug Sen­si­par, which earned $1.4 bil­lion.

This was one of Am­gen’s top Phase III ef­forts in the pipeline. It scored a suc­cess on its PC­SK9 cho­les­terol drug, but it’s been a dis­ap­point­ment in its ear­ly days on the mar­ket.

Bri­an Sko­r­ney, Baird an­a­lyst

Baird’s Bri­an Sko­r­ney not­ed the ab­sence of any ex­pla­na­tion from Am­gen, and then of­fered his opin­ion that the agency might have been put off by safe­ty is­sues. His com­ment:

In the head-to-head study, Sen­si­par and Parsabiv looked sim­i­lar, with Parsabiv show­ing high­er rates of treat­ment-emer­gent AEs (93% vs. 90%) over­all, with a slight­ly low­er rate of se­ri­ous ad­verse events (25% vs. 27%). Specif­i­cal­ly, Parsabiv showed high­er in­ci­dence of hypocal­cemia (5% vs. 2.3%), car­diac fail­ure (3% vs. 0.6%), and fa­tal ad­verse events (2.7% vs. 1.8%). It re­mains un­clear whether or not these dif­fer­ences fac­tored in­to the FDA’s de­ci­sion. It is pos­si­ble that the mod­est in­crease in these ad­verse events out­weighed the ben­e­fits pro­vid­ed on sec­ondary end­points and in the dif­fer­ing ad­min­is­tra­tion, in the FDA’s opin­ion. It’s al­so pos­si­ble that this is just a mi­nor CMC is­sue and can be quick­ly re­solved.

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

US regulators cleared an ultra-rare drug from Pharming Group, by way of Novartis, on Friday afternoon.

The Dutch biotech said the FDA greenlit leniolisib for an immunodeficiency disease known as activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome, or APDS. People 12 years and older can receive the oral drug, to be marketed as Joenja, beginning early next month, Pharming said, five days ahead of the decision deadline set by the FDA as part of a priority review.