A lot has happened since we last addressed new
biosimilar developments in January
2018. In the
intervening months, there have been many significant developments related to
FDA’s implementation of an efficient regulatory program for biosimilar products
and the abbreviated BLA (aBLA) review process. Today we’re going to recap some
of what has transpired over the past 5 months in the biosimilars space in an
attempt to get our readers caught up.
Two New Approvals
Two important biosimilar “firsts” have been achieved
by the FDA and the respective product developers/aBLA sponsors. On May 15, FDA
approved the first biosimilar of Epogen®/Procrit® (epoetin alfa) for the
treatment of anemia caused by chronic kidney disease and chemotherapy –
developed by Pfizer/Hospira and called Retacrit (epoetin alfa-epbx). Then on
June 4th, the Agency approved Mylan/Biocon’s aBLA for Fulphila
(pegfilgrastim-jmdb), the first biosimilar to Neulasta® (pegfilgrastim) to
decrease the chance of infection in certain patients with non-myeloid cancer
who are receiving myelosuppressive chemotherapy.
This brings the total number of FDA-licensed
biosimilars to 11 – although only 3 have been launched commercially due to
ongoing patent litigation, settlements, and such. You can see an updated
version of our Status of Biosimilars Chart here.
Interestingly, the aBLA for Fulphila
(pegfilgrastim-jmdb) did not go through the advisory committee process like we
has seen occur for every prior application for the first-to-be-reviewed
biosimilar of a reference biosimilar product. It remains to be seen whether
that administrative decision by the Agency was (a) due to its familiarity with
the related molecule filgrastim – a biosimilar version was approved in 2015 as
the first-ever aBLA, and several more filgrastim aBLAs are presently under
review – (b) possibly related to the increased political pressure on FDA and
other components with the Department of Health and Human Services (HHS) to
deliver on President Trump’s promise to tackle high drug prices, or (c)
something else entirely. As of the date of this posting, no administrative
records or review documents for the Fulphila aBLA have been released publicly.
Revised Guidance
Also on June 4, FDA issued a revised version of the
draft guidance document Formal
Meetings Between the FDA and Sponsors or Applicants of BsUFA Products. The revisions were made to take into account BsUFA
II, enacted last year as part of the FDA Reauthorization Act, and the
performance goals under the current iteration of the Biosimilar User Fee
Program.
Monograph Developments
In March 2018, the CBER and CDER Directors jointly
sent a letter to USP, the private standard-setting body, regarding USP’s
stated intent to create biological drug product monographs. In short, Dr. Peter
Marks and Dr. Janet Woodcock expressed their concerns that the USP proposal, if
implemented, could “delay or impede licensure of a biosimilar that meets the
licensure requirements under section 351(k) of the [Public Health Service] Act”
but that does not necessarily “match the standards in the USP monograph
associated with the reference product.”
USP initially responded to the concerns on April 2,
2018 by issuing a public
statement that it
“will not develop a new monograph for a biologic unless there is stakeholder
consensus supporting its creation, including the support of FDA. USP’s proposed
revision is intended to align compendial names with FDA’s biologics naming
approach and avoid potential issues for manufacturers and other stakeholders.”
The Chief Operating Officer of USP, Dr. Ronald Piervincenzi, also responded
directly to the FDA center directors in a letter dated
April 27, 2018. It
has been quite fascinating to watch the debate between two entities with such
importance for drug and biologic developers take place so publicly over the
past several months. Rest assured that the conversations regarding biological
product standards are not over.
Final Thoughts
We’ll close this by noting that biosimilars, as part
of the FDA’s overall Drug Competition Action Plan (see a prior post here), have continued to receive a lot of press attention
but have had little substantive change to date. In conjunction with the
announcement of the HHS Blueprint to Lower Drug Pricing to much fanfare on May
11, 2018 (see here), FDA Commissioner Gottlieb issued his own concurrent
statement that focused on steps the Agency is taking to strengthen and advance
the generic and biosimilar markets.
Dr. Gottlieb has been touting the “Biosimilar Action
Plan” for several months now, so we expect to see some concrete actions soon
under this so-called BAP. While the plan is expected to include changes in the
proposed interchangeability standards that were issued as draft guidance in the
waning days of the Obama Administration, we know little about the Agency’s
plans for other biosimilar-specific actions.
Mintz Levin Cohn Ferris Glovsky and Popeo PC - Joanne
Hawana - Lexology
