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As Pfizer's HIV Drug Selzentry Gains FDA Approval, Monogram Preps for Trofile Launch

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This story was updated to include pricing information for Selzentry.
 
Language in the US Food and Drug Administration-approved labeling for Pfizer’s HIV drug Selzentry, which recommends doctors establish the tropism status of their patients prior to administering the drug, may help Monogram Biosciences garner reimbursement for its Trofile assay, Monogram officials said this week.
 
In conjunction with the FDA approval this week of Selzentry, also called maraviroc, Monogram held a call with investors to introduce the launch plans for its Trofile assay, a test that Pfizer used in clinical trials to determine which patients would benefit from treatment with its drug.
 
“We’ve had numerous discussions with payors from payor advisory boards to try to understand what they thought from a generic basis to [a] more tactical [basis] as we got closer to the launch,” said Monogram Chief Commercial Officer William Welch during the call. “But now that we’ve got the label, of course we’ll go right at them as this thing goes forward. All the conversations have been easily understood with the link between the drug and the diagnostic. … The conversations have gone quite well.”
 
According to Alfred Merriweather, Monogram’s chief financial officer, the company will begin marketing the test immediately to give physicians a head start to determine the tropism status of their patients before Pfizer launches Selzentry in mid-September. Company officials expect the Centers for Medicare & Medicaid Services and private payors to begin reimbursing for the test, priced at $1,960, within the next two months. State insurers will follow suit by the second quarter of next year, Welch expects.
 
Selzentry, for use in combination with other antiretroviral drugs to treat CCR5-tropic HIV-1, received priority review at the FDA. The drug, indicated for treatment-experienced HIV patients, “is the first in a new class of drugs designed to slow the advancement of HIV,” the FDA said in a release announcing the approval of the drug.
Although, in the US, Pfizer and Monogram have their own sales forces for marketing the drug and diagnostic separately, Pfizer’s reps will be equipped with an information sheet on the Trofile assay and be able to point physicians to Selzentry’s label to highlight the need to establish the tropism status for patients prior to maraviroc treatment.
 
“They won’t promote the test per say, but certainly they should explain the label to doctors and tell them [Trofile is] the tropism test that’s been used in the clinical trials,” Merriweather told Pharmacogenomics Reporter this week.
 
Trofile is a phenotypic assay that confirms whether an individual’s virus exclusively uses the CCR5 co-receptor, a protein on the surface of certain immune cells, and thus will respond to the drug. According to Pfizer, between 80 percent and 85 percent of treatment-naive HIV patients and about half of the treatment-experienced population fall into this category, called R5-tropic.
 
However, if the assay finds that HIV uses the CXCR4 co-receptor (non-R5 tropic) or uses both the CXCR4 and CCR-5 receptors (dual/mixed tropic), the patient will not benefit from the drug.
 
“Tropism testing and treatment history should guide the use of Selzentry,” the drug’s label states. “Use of Selzentry is not recommended in patients with dual/mixed or CXCR4-tropic HIV-1 as efficacy was not demonstrated in a Phase II study of this patient group. … In the majority of cases, treatment failure on maraviroc was associated with detection of CXCR4-using (i.e., CXCR4- or dual/mixed-tropic) virus which was not detected by the tropism assay prior to treatment.”
 
Unlike most HIV drugs that fight the virus inside white blood cells, Selzentry prevents the virus from entering the cells by blocking the CCR5 co-receptor. In a statement, the FDA estimated that among patients who have previously received HIV medications, approximately 50 percent to 60 percent have circulating CCR5-tropic HIV-1.
 
“This is an important new product for many HIV-infected patients who have not responded to other treatments and have few options,” said Steven Galson, director of FDA’s Center for Drug Evaluation and Research, in a statement.
Pfizer and Monogram in May 2006 announced a non-exclusive collaboration to make Monogram’s Trofile assay available for patients worldwide. Pfizer at the time also invested $25 million in Monogram [see PGx Reporter 05-10-05]. Selzentry is also part of an expanded access program in over 30 countries, where Pfizer has been providing the drug until it receives regulatory approval. Outside the US, Pfizer will market Trofile.
 
Recommending diagnostic testing in drug labeling has not necessarily been effective in getting physicians to use genetic tests. However, payors have said that if a drug’s label discusses the benefits of a certain type of testing, then they will be more likely to reimburse for such a product. FDA officials, on the other hand, have noted that the best way to ensure physician adoption of a diagnostic is through Rx/Dx co-development, as is the case with the Selzentry/Trofile combination [see PGx Reporter 01-03-2007].
 
Reimbursement, Adoption Confidence
 
As a result of the recommendation for tropism testing in maraviroc’s label, Monogram officials remained confident that the test would be broadly adopted by doctors and reimbursed by the majority of payors.
 
“The FDA label clearly states that you should know a patient’s tropism prior to initiating therapy and also patient history. We believe that the risk benefit for testing is quite high,” Welch reminded investors. “In treatment-experienced patients, about 50 percent of them are CCR5 positive. Knowing a person’s tropism [status] is pretty important. If one of the drugs were to fail in an HIV regimen then the entire regimen would fail. So, I think physicians will look to the labeling for advice.”
 
Merriweather said that Monogram will start discussions with payors at the end of August regarding reimbursement for the first orders of the test. “We’ll be working with payors on our initial plans to minimize the time in the submission of claims and establishment of reimbursement,” Merriweather said. “We anticipate that some payors may make quick coverage decisions such that within a month or two initial revenues can be recorded, with acceleration as additional payors establish coverage.”
 
The level of reimbursement on the $1,960 list price will depend on the payor class, Welch explained. The company is betting that Medicare and private payors will likely pay at list price, while state payors will wait to reference the national coverage limit and pay between 70 percent and 80 percent of that price.
 
“We know states will use that price as a reference to get a lower price; normally 80 percent would be [the price] for Medicaid,” Welch said. “So, overall, the price we usually get from the list price for our products is somewhere between [the] 70 percent to 75 percent range. We think Trofile will probably meet this range.”
 
To determine the price of the test, Welch said Monogram factored in the cost to develop, produce, distribute, and make Trofile available to clinicians for patient care. The company also conducted market research with payors and physicians, and sought input from stakeholders.
 
“We know the pharmacoeconomics would support a higher Trofile cost,” Welch said. “We plan to finalize the pharmacoeconomic analyses now that maraviroc is going to be available. We’ll know what the drug cost is and the overall therapy and the value of Trofile.”
 
He added that the list price is in the “sweet spot” for investors, patients, providers, and advocates.
 
However, during a meeting of the Antiviral Drugs Advisory Committee in late April, committee members observed that resistance or co-receptor switching may cause patients to stop responding to maraviroc and may require them to be periodically tested with Monogram’s Trofile assay.  This raised concerns that the additional cost of periodic testing may discourage patients from using the drug [see PGx Reporter 05-02-2007].
 

“We know the pharmacoeconomics would support a higher Trofile cost.”

Pfizer has set the wholesale acquisition cost for Selzentry to $29 per day for both the 150 and 300mg twice a day dosing regimens. The WAC price is the drug manufacturer’s list price for a drug to wholesalers or direct purchasers in the US. “We don't and can't speculate on [the price to patients] as the price will likely vary from payor to payor and the cost to patients is dependent on their coverage,” a Pfizer spokesperson told Pharmacogenomics Reporter over e-mail.
 
Although Pfizer will not launch its product before mid-September, Monogram is beginning conversations with physicians this week to prepare for an immediate launch of its test using a 50-person sales team. Merriweather told Pharmacogenomics Reporter this week that the company is using the lag time to reach out to physicians and encourage them to establish the tropism status of their patients.
 
“In our case, the test is ready, we’re ready, we got our sales force trained,” Merriweather said. “There is a two-week turnaround time on our test. So, if we go out and talk to doctors in a week or so, and they identify patients and submit samples within the next week or two, it will take a couple of weeks to get the results back to the doctor. By early September the doctor can be making a decision to prescribe maraviroc or not.
 
“By having our test available a little bit earlier, we’re allowing doctors to go ahead and start screening their patients. … That actually dovetails quite nicely,” Merriweather added.
 
Future Profitability
 
During the call, Monogram CEO William Young acknowledged that Selzentry’s approval “holds the potential to transform [Monogram’s] HIV business, providing a significant new revenue stream that will be layered on top of our existing revenues.”
 
The company recently reported $9.7 million in revenue for the three months ended June 30. Total revenue in the second quarter of 2006 was higher at $13.4 million, since during that time Pfizer's Phase III trial for maraviroc was still in process.
 
Outside of its agreements with Pfizer, the Trofile assay is also being used as a companion diagnostic for several other HIV drugs under development, notably a pair of novel integrase inhibitors made by Merck and Gilead [see PGx Reporter 03-21-2007]. These deals, if successful, also hold promise for future earnings for the company.
 
“Our Trofile assay is the only available tropism test, and as a reminder, it has been the only test that’s been used in every Phase II and Phase III study of CCR5 antagonist to date,” Young said. Company officials also acknowledged during the call that they are developing next-generation Trofile assays.
 
The agency approved maraviroc based on 24-week data from two double-blind, placebo-controlled studies. In the trials, approximately twice as many patients receiving maraviroc with optimized background therapy had undetectable viral load at 24 weeks versus optimized background therapy alone. These studies are ongoing since “longer term data will be required before the FDA can consider traditional approval for Selzentry,” Pfizer said in a statement.
 
Selzentry’s label includes a boxed warning about liver toxicity and a statement in the Warnings/Precautions section about the possibility of heart attacks. The most common adverse events reported with maraviroc were cough, fever, upper respiratory tract infections, rash, musculoskeletal symptoms, abdominal pain, and dizziness.
 
“The safety and efficacy of Selzentry have not been established in treatment-naïve adult patients or pediatric patients,” the label states. Pfizer has said it plans to seek a claim for Maraviroc in treatment-naïve patients, for which the pivotal trial is already enrolled. The company has said it expects to file this additional indication with the FDA in mid-2007.

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