In its briefing document, the US Food and Drug Administration
(FDA) recently raised issues regarding the safety of Genzyme, a
) company, and partner
Isis Pharmaceuticals Inc.
) candidate Kynamro (mipomersen).
The companies are seeking FDA approval for the use of Kynamro for
the treatment of patients with homozygous familial
hypercholesterolemia (HoFH). Kynamro will be reviewed by an FDA
advisory panel on October 18, 2012. A response from the FDA is
expected by January 29, 2013. Approval would trigger a $25
million milestone payment from Sanofi.
The FDA raised concerns regarding liver-related adverse effects
associated with Kynamro in the briefing document. In the pooled
phase III results, it was observed that a higher number of
adverse events were related to elevations in serum transaminase
levels and hepatic steatosis in the Kynamro arm as compared to
In the Kynamro arm, the incidence of reported benign and
malignant neoplasms (3.1%) was also higher, when compared to
placebo (0.9%). Additionally, the FDA noted that Kynamro
increased the incidence of hemangiosarcomas and hepatocellular
adenomas/carcinomas in animal studies.
Investors have reacted negatively with Isis Pharma's share price
plunging 21.9% on the news.
Kynamro is the lead pipeline candidate at Isis Pharma. Isis
Pharma and Genzyme are also seeking approval for the candidate in
the EU for HoFH and severe heterozygous familial
hypercholesterolemia (HeFH) - the companies are expecting to
launch Kynamro later this year pending EU approval.
Isis and Genzyme are conducting a 12-month study (FOCUS FH -
saFety and atherOgeniC lipoprotein redUction of mipomerSen in
FH). This study is being conducted to support the expansion of
the FH patient population to include severe HeFH in the US,
support an alternative dosing regimen (three times a week), and
broaden the FH indication beyond severe in Europe. Successful
development could allow Kynamro's label expansion in the
Isis Pharma's agreement with Genzyme dates back to 2008. As per
the terms of the deal, Isis will not only receive
commercialization and development milestones, it will also split
net profits with Sanofi on Kynamro (70% - Sanofi, 30% - Isis)
until worldwide sales eclipse $2 billion. Thereafter, the
companies will split profits on Kynamro 50/50.
Although we believe Kynamro has blockbuster potential, we remain
worried that concerns regarding the safety profile of the drug
could limit its commercial potential once launched.
We currently have a Neutral recommendation on Isis Pharma, which
carries a Zacks #4 Rank (short-term Sell rating). We expect
investor focus to remain on the outcome of the FDA panel meeting.
We note that the FDA's Endocrinologic and Metabolic Drugs
Advisory Committee will be reviewing
Aegerion Pharmaceuticals, Inc
) lomitapide on October 17 for the treatment of adult patients
AEGERION PHARMA (AEGR): Free Stock Analysis
ISIS PHARMACEUT (ISIS): Free Stock Analysis
SANOFI-AVENTIS (SNY): Free Stock Analysis
To read this article on Zacks.com click here.