Qsymia Uptake Slow, Steady, but Will It Win Obesity Race?

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"Dark horse Contrave has gained some ground through faster patient accrual and negotiations by its maker, Orexigen Therapeutics Inc., with the FDA for faster resubmission of its new drug application."

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Four weeks after its launch, 2,000 patients were taking obesity drug Qsymia (phentermine/topiramate), from Vivus Inc., with new patient starts slowing from an initial four- or five-fold increase to a 27–33% increase from week three to week four, according to IMS and Wolters Kluwer weekly prescription data.

Uptake is slower than some investors expected, and in the meantime, dark horse Contrave (naltrexone/buproprion) has gained some ground through faster patient accrual and negotiations by its maker, Orexigen Therapeutics Inc., with the FDA for faster resubmission of its new drug application (NDA).

"We view these numbers as another good week of new patient starts for Qsymia, even though the 27-33% increase reported by the two vendors may seem disappointing to some investors that may have anticipated the four- to five-fold increase in earlier weeks to become a trend," wrote Yatin Suneja, a Cowen and Co. analyst.

IMS reported that in the fourth week of its launch, Qsymia logged 1,626 new prescriptions, which was a 27% increase over those estimated for the third week.

Wolters Kluwer found 1,935 new prescriptions for the same period, a 33% jump.

The capture rate for those numbers is not reported, meaning that they are most likely a more accurate measure of trends than real patient numbers.

Suneja said the figures represent 813 and 968 new patient starts, respectively, because new patients receive two prescriptions when beginning the drug. The first is a starting prescription for low-dose Qsymia (2.75 mg phentermine/23 mg topiramate) for the first two weeks, and the second prescription is for mid-dose (7.5 mg phentermine/46 mg topiramate) for use after two weeks, minimally for the next four weeks.

The patient is evaluated for response to the drug after two weeks, and then, if necessary, boosted to the midrange dose.

After 12 weeks on the drug, if the patient has not lost 3% of body weight, that subject gets another 12-week trial at the highest dose, after which the test for continuation is 5% loss of body weight. The total trial period is 28 weeks.

However, J. P. Morgan's Cory Kasimov cautioned that not all physicians are following those prescribing guidelines. "Apparently not all physicians are writing both initial scripts at the same time (some will do just the low dose at first and others may bypass the low dose). Thus, in addition to the difficulties in assessing capture rate, estimating the number of new patients on drug is not as straightforward as dividing the [new prescriptions] in half," Kasimov wrote.

Although the slower-than-expected uptake, combined with last week's denial by the European Committee for Medicinal Products for Human Use (CHMP), appears to be a major setback for the company, Suneja pointed out that it is still too early to get a good read on the launch, and that the launch is being managed through a mail-order pharmacy. "We're dealing with a mail-order pharmacy launch, which may make estimates even less predictive of actual scripts," Suneja wrote. (See BioWorld Today, Oct. 22, 2012.)

Reimbursement trends were a strong, and possibly widely overlooked, positive for Mountain View, Calif.-based Vivus. Reimbursement by commercial payers increased to 56% in the fourth week, up from 53% the third week and 36% in the second week.

"We previously confirmed with management that these data (at least at week 2) were representative. Moreover, we also previously reported from the Obesity Society last month in San Antonio that payers were aggressively reaching out to Vivus for information on Qsymia," Kasimov wrote.

In July, Vivus projected reimbursement at about 30% of payers one year from launch, and growing thereafter. That was based on reimbursement rates for obesity treatments in general, which run about 30%.

Instead, payers have moved quickly to reimburse Qsymia, exceeding Vivus' one-year goal by the second week, and beating it soundly by week four.

Vivus' stock (VVUS:NASDAQ) lost $1.12 to close Monday at $19.48.

Orexigen Gaining Ground

Orexigen said it received a response from the FDA's Center for Drug Evaluation and Research indicating that the agency highly supports discussions with the company about a faster path to resubmission of its NDA for Contrave.

The company may be able to submit the NDA in advance of reporting interim data from the Light Study, which is accruing patients faster than expected.

The Light Study is a cardiovascular outcomes trial requested by the FDA in January 2011 when it rejected the San Diego-based company's submission for Contrave. (See BioWorld Today, Feb. 1, 2011.)

That would mean that the interim analysis would come out while the FDA is reviewing the new submission, and if everything goes well, putting the agency in a position to act on Contrave quite soon after those interim data are reported.

The FDA denied Orexigen's request to be considered for approval on the basis of existing clinical data along with a postmarketing requirement to submit the interim data from Light shortly after approval.

"We remain highly confident in Contrave's ultimate approvability, as we see it as highly unlikely that the product increases the risk of major adverse [cardiovascular] events," Kasimov wrote. "In our view, the magnitude of the valuation discrepancy between Orexigen and the other two major obesity players [Arena Pharmaceuticals Inc. and Vivus] is unwarranted, and we expect this gap to narrow over time."

San Diego-based Arena and partner Eisai Inc. gained approval of obesity drug Belviq (lorcaserin) in June. (See BioWorld Today, June 28, 2012.)

Orexigen said enrollment in the Light Study has exceeded 7,000 patients and it will continue enrolling patients to reach 9,000 by the end of 2012. That means the time to accrual of the 87 major adverse cardiovascular events needed for the interim review also would occur earlier, by about two months, or the second quarter of 2013.

The company previously had expected that interim analysis by the middle of 2013.

Catherine Shaffer
BioWorld

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