Full article reprinted from "The Pink Sheet" DAILY November 3, 2010
Amylin's Byetta cleared for first-line use without a black box stigma, but sales may still not get a lift. read more...
Full article reprinted from "The Pink Sheet" DAILY November 3, 2010
Analysts doubt that FDA's approval of Amylin and Eli Lilly's Byetta injection as a monotherapy type 2 diabetes will give sluggish sales much of a lift, but the lack of a black box warning for pancreatitis is reassuring and could bode well for other drugs overshadowed by that condition.
Approval for a twice-daily Byetta (exenatide) injection as a standalone treatment for adults came on Oct. 30, two days before Amylin announced a major partnership deal to develop obesity drugs with Takeda.
Byetta had already been approved as an add-on therapy with metformin, a sulfonylurea, or a thiazolidinedione, and the monotherapy application was long overdue, given that the drug had a user fee date of December 2008.
FDA had also been working on revisions to safety information in the Byetta label to address the pancreatitis risk and it's likely that this caused the delay-- changes were cleared and published at the same time as the monotherapy indication.
Byetta's label now states that, based on post-marketing data, the drug is associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. Doctors are advised to observe patients for signs of pancreatitis and halt treatment if symptoms arise.
The label also includes a warning on renal impairment, in response to 78 reports of problems with kidney function by Byetta users from April 2005 through October 2008.
Byetta should not be used in patients with severe renal impairment (defined as creatinine clearance less than 30 mL/min) or end-stage renal disease. It should be used with caution in patients with renal transplantation. Furthermore, the label notes that the most common side effects associated with Byetta-- nausea, vomiting, and diarrhea--may contribute to the development of altered kidney function.
Monotherapy clearance not expected to lift sales
In a press statement, Amylin said the "expanded indication gives physicians the option to prescribe Byetta as a first-line treatment, increasing the number of patients who may benefit from the medication and providing an opportunity to treat patients with Byetta earlier in the disease."
Whether the added indication will do much for sales remains to be seen. Take-up of the GLP-1 agonist has been disappointing and Amylin has restructured a number of times, including hundreds of job cuts, and revamped its sales and marketing strategies to give scripts a boost. Byetta sales amounted to $670 million in 2008, not far up from $636 million in the previous year.
Many see the drug's future as lying with Byetta LAR, the long-acting, once-weekly form of exenatide, which was submitted for approval to the FDA for approval in May 2009 by Amylin with partners Lilly and Alkermes.
Pancreatitis is a risk in the diabetes patient population generally and the condition has overshadowed a number of drugs, including Byetta. Using data from UnitedHealth, Amylin has conducted an epidemiology study that showed Byetta does not increase risk of acute pancreatitis compared to other type 2 diabetes medications, but it's unclear whether this has been enough to fully reassure doctors.
"The win for Amylin is that the pancreatitis update did not result in a black box," wrote Kelly Close, president of the San Francisco-based diabetes consultancy Close Concerns in an Oct. 31 note. "This should be very encouraging to doctors in particular, who have been dogged by malpractice lawyers."
Similarly, Baird analyst Thomas Russo noted that the inclusion of a bolded warning as opposed to a boxed warning for pancreatitis is good news for the product and could mean that other GLP-1 agonists-- Byetta LAR, Novo Nordisk's Victoza (liraglutide) and Roche/Ipsen's taspoglutide-- could get labels with similarly benign language.
Another drug that could benefit is Merck's dipeptidyl peptidase-4 inhibitor Januvia (sitagliptin), which was also recently linked to a possible risk for pancreatitis, raising the specter of a black box warning.
Amylin has suggested that Byetta could get a boost from the resolution of the label issue, but the real-world impact is unclear, according to Russo. In the most recent week for which figures were available, Byetta prescriptions were still about percent below their early-2008 peak. "Investors will take a wait-and-see approach," he wrote.
In the meantime, the monotherapy indication is more important in the future for the LAR than for Byetta, Russo concluded.
Cannacord Adams analyst Adam Cutler observed in a Nov. 2 note to investors that Byetta sales and prescription trends have been flat and are unlikely to change significantly based on the new label. "We suspect that physicians who wanted to prescribe Byetta as monotherapy were likely already doing so," he wrote.
J.P Morgan's Cory Kasimov has "minimal expectations for a reacceleration of sales…We still expect Byetta's commercial hurdles (2x/day injection and GI/nausea tolerability issues) to remain an impediment to use," the analyst wrote in a Nov. 2 investor note. "In our view, the real hope is that this will facilitate a broader label for exenatide once-weekly, when and if it's approved."
New warning on kidney damage called "non-alarming"
Analysts weren't fazed by the new warning on kidney damage in the new Byetta label. For example, Kasimov referred to the label language as "a non-alarming description warning against use in patients with severe renal impairment."
In a Nov. 2 release, the FDA warned health care professionals and patients taking Byetta to pay close attention to any signs or symptoms of kidney problems.
"Patients also should be aware that problems with kidney function could lead to changes in urine color, frequency of urination or the amount of urine, unexplained swelling of the hands or feet, fatigue, changes in appetite or digestion, or dull ache in mid to lower back," according to the statement.
To put the problems in context, the agency noted that it received 78 reports in the three-year period studied, out of over 7 million prescriptions dispensed. Some cases occurred in patients with pre-existing kidney disease or in patients with one or more risk factors for developing kidney problems.
- Emily Hayes
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