Isis Pharmaceuticals $ISIS and Sanofi $SNY announced the FDA approval of KYNAMRO (mipomersen) for the treatment of homozygous familial hypercholesterolemaia on January 29, 2013 and held a conference call the next day. This approval followed the December 2012 approval of JUXTAPID (lomitapide) from Aegerion Pharma for the same patient population and the October 2012 FDA Advisory Committees that voted in favor of both drugs. My notes from the webcast can be found below. Keep in mind this is reporting what management said on the call, which always includes a fair amount of "ISIS speak" statements that often later turn out to be hogwash, as I have noted when possible.Related Content:(Continue reading for full post)
The race to developed novel cholesterol-lowering monoclonal antbodies targeting PCSK9 is heating up as Regeneron REGN and Sanofi SNY are the first to embark on a massive phase 3 program. While this battle is the realm of the big pharmas, small-cap biotech investors should also track the progress of these hypercholesterolemia drugs which are competitors in the familial HoFH/severe HeFH arena to KYNAMRO/mipomersen (developed by Isis Pharma ISIS with SNY - note Isis abandoned their PCSK9 antisense program), lomitapide (Aegerion AEGR), and ALN-PCS (RNAi against PCSK9 from Alnylam ALNY, which is seeking a parter for phase 2 development). Continue reading below the jump for the latest updates from 3q-2012 earnings conference calls about these candidates.
Quick notes from the Isis Pharma $ISIS conference call after tepid endorsement of KYNAMRO (mipomersen) by the FDA metabolic and endocrine products advisory committee. You can find more of my commentary on this event (as well as competitor Aegerion Pharma $AEGR and their drug lomitapide) on the Chimera Research Group blog.
- US - 200-300 pts on apheresis out of 12000-15000 eligible (don't have specific # that are hoFH - is believed that about 10% of them can access and tolerate the procedure). Therefore most on apheresis are actually heFH
- FOCUS trial - SPA negotiated with understanding that outcome trial not possible in severe HeFH either. Would you consider adding atherosclerosis measurement etc? We considered imaging, but not acceptable endpoint to regulators. [context for this is a dissatisfaction expressed by the AdComm regarding the LDL endpoint, particularly for any population broader - and lower risk - than homozygous familial hypercholesterolemia]
- refused to compare/contrast US/EU regulatory process. "it is proceeding" [context: it was clear form the panel that the broader label in the EU sought by ISIS/Sanofi was in grave jeopardy - a fact that was finally admitted much later on Isis's 3q-2012 earnings conference call]
- nothing about the panel causes us to change our estimates of # of pts and # of accessible pts [complete BS of course...]
Both Aegerion Pharma AEGR (lomitapide) and Isis Pharma ISIS (KYNAMRO/mipomersen with partner Sanofi SNY / Genzyme) will face FDA advisory committees for the homozygous familial hypercholesterolemia (HoFH) drugs this week:
I compiled a few key figures from the FDA briefing document for AEGR, highlighted my notes from the FDA reviewers, and added a few comments of my own that relate to the panel discussions for both AEGR and ISIS. Sorry it is a bit disorganized, but I will try to go back and clarify further - keep reading here for all the details.
- 10/15: AEGR briefing documents released
- 10/16: ISIS briefing documents released
- 10/17: AEGR panel presentations, discussion and vote
- 10/18: ISIS panel presentations, discussion and vote
Aegerion Pharma $AEGR held its first quarter 2012 earnings call on May 3rd. Here are a few quick notes regarding their drug candidate lomitapide and its potential competitor KYNAMRO (mipomersen) from Isis Pharma $ISIS.
- US NDA and EU MAA have been accepted for review
- Expect FDA advisory committee meeting late 3q or early 4q 2012
- Expect US approval late 2012 and EU approval first half 2013
- Project profitability in 2014
- Working on patient registry for homozygous familial hypercholesterolemia (HoFH), won't say how many patients are on it until closer to launch
- Expect mipomersen and lomitapide to be revieweed at same panel. Topics of discussion could include trial design, liver safety, REMS
- AEGR has submitted a proposed REMS to FDA in NDA filing focused around strict on-label use and monitoring of liver enzymes.
- Don't see a place for PCSK9 drugs in HoFH
- Now can't forecast a date for access program/reimbursement in France (had been projecting by year-end 2011)
- Need to reformulate before starting pediatric trials -won't start until 2013, and probably after initial regulatory decisions. Need to get same bioavailability, stability, palatability for whatever presentation given to kids - so even if plan to open capsules and mix with food, would have to do the work. Liquid formulation has not been tried but should be technically feasible.
- Market size estimate ~3000 patients in US holds up across multiple methods of calculation so far.
- In these patients, neither mipomersen nor lomitapide is going to get all patient to goal LDL levels
- Intellectual property: Excited about patent issued in 2011 (administration patent through 2025-2026 in US/EU). Composition of matter (COM) patent expires in 2015, Hatch-Waxman extension through mid-2020. 10 years EU market exclusivity. Patent term extension for COM in US "yet to be determined"