Obesity Drug Resubmitted for FDA Approval

Vivus’s resubmission of the new drug application for its obesity drug Qnexa (topiramate/phentermine) is for a severely limited patient population – excluding all women under 55 years of age.

The price of the deal the company reached with the Food and Drug Administration in September on a plan for an early new drug application (NDA) resubmission was that it would have to restrict the patient population – excluding women of childbearing age to avoid the risk of birth defects in babies born to women taking the drug.

Chief Financial Officer Timothy Morris told "The Pink Sheet" that the restriction would mean the drug is off limits to any woman under the age of 55. By eliminating patients who could become pregnant, the company sidesteps the concerns about teratogenicity raised in the FDA’s "complete response" letter rejecting initial approval on Oct. 28, 2010.

While the company says that the drug can be used in some 80 million Americans, it will not be able to market the drug to a prime demographic.

Mr. Morris said there will be some exceptions; women under 55 will be able to get a prescription if their doctor believes they do not have childbearing potential.

And the company is looking ahead to expand the indication; Vivus is awaiting the results of FORTRESS, a post hoc analysis that will take a closer look at the effects of topiramate on women who bore children while taking the drug. The results are expected in December, and Vivus will submit top-line data to the FDA at that time.

According to the Oct. 17 NDA submission, Qnexa will be indicated for obese patients with a body mass index (BMI) over 30 kg/m² or overweight patients with a BMI over 27 who do not have childbearing potential, and who have at least one comorbidity, like high blood pressure, type 2 diabetes, or abdominal obesity.

On top of the original datasets, the filing adds 2-year data from the SEQUEL study – based on a 1-year extension of a subset of patients that completed the 56-week CONQUER study. The NDA also includes study results from a recent sleep apnea trial to help support the company’s claims that Qnexa does not contribute to heart disease or an elevated heart rate. The company is also studying the drug for sleep apnea and diabetes.

Vivus submitted a Risk Evaluation and Mitigation Strategy (REMS) as well. Mr. Morris would not comment on what the REMS included, but said that Vivus is waiting for feedback from the agency on its proposal.

Prior to last year’s action letter, Vivus had proposed a REMS plan that included a voluntary pregnancy registry, because 34 women in the Qnexa clinical trials became pregnant despite measures taken by the company to keep accidental pregnancies from occurring.

Qnexa is a combination of phentermine, an appetite suppressant, and topiramate, a form of Johnson & Johnson’s antiseizure medication Topamax. Both components are available as generics. In March, the FDA reclassified topiramate as Pregnancy Category D because of the drug’s potential to cause birth defects, usually cleft lip or palette. Warnings are now included on the labels of all forms of the drug, and doctors are instructed to evaluate whether the benefits are worth the risks when treating a woman of childbearing age. A Category D warning means that there is now human evidence of the risk of birth defects, as opposed to the Category C warning topiramate previously had, which was only supported by evidence in animal studies.

The FDA told the company that its Endocrine and Metabolic Advisory Committee will host a panel in the first quarter of 2012 to reassess the risks associated with the drug. A panel in July 2010 voted 10-6 against approval of the obesity drug.

This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

Vivus’s resubmission of the new drug application for its obesity drug Qnexa (topiramate/phentermine) is for a severely limited patient population – excluding all women under 55 years of age.

The price of the deal the company reached with the Food and Drug Administration in September on a plan for an early new drug application (NDA) resubmission was that it would have to restrict the patient population – excluding women of childbearing age to avoid the risk of birth defects in babies born to women taking the drug.

Chief Financial Officer Timothy Morris told "The Pink Sheet" that the restriction would mean the drug is off limits to any woman under the age of 55. By eliminating patients who could become pregnant, the company sidesteps the concerns about teratogenicity raised in the FDA’s "complete response" letter rejecting initial approval on Oct. 28, 2010.

While the company says that the drug can be used in some 80 million Americans, it will not be able to market the drug to a prime demographic.

Mr. Morris said there will be some exceptions; women under 55 will be able to get a prescription if their doctor believes they do not have childbearing potential.

And the company is looking ahead to expand the indication; Vivus is awaiting the results of FORTRESS, a post hoc analysis that will take a closer look at the effects of topiramate on women who bore children while taking the drug. The results are expected in December, and Vivus will submit top-line data to the FDA at that time.

According to the Oct. 17 NDA submission, Qnexa will be indicated for obese patients with a body mass index (BMI) over 30 kg/m² or overweight patients with a BMI over 27 who do not have childbearing potential, and who have at least one comorbidity, like high blood pressure, type 2 diabetes, or abdominal obesity.

On top of the original datasets, the filing adds 2-year data from the SEQUEL study – based on a 1-year extension of a subset of patients that completed the 56-week CONQUER study. The NDA also includes study results from a recent sleep apnea trial to help support the company’s claims that Qnexa does not contribute to heart disease or an elevated heart rate. The company is also studying the drug for sleep apnea and diabetes.

Vivus submitted a Risk Evaluation and Mitigation Strategy (REMS) as well. Mr. Morris would not comment on what the REMS included, but said that Vivus is waiting for feedback from the agency on its proposal.

Prior to last year’s action letter, Vivus had proposed a REMS plan that included a voluntary pregnancy registry, because 34 women in the Qnexa clinical trials became pregnant despite measures taken by the company to keep accidental pregnancies from occurring.

Qnexa is a combination of phentermine, an appetite suppressant, and topiramate, a form of Johnson & Johnson’s antiseizure medication Topamax. Both components are available as generics. In March, the FDA reclassified topiramate as Pregnancy Category D because of the drug’s potential to cause birth defects, usually cleft lip or palette. Warnings are now included on the labels of all forms of the drug, and doctors are instructed to evaluate whether the benefits are worth the risks when treating a woman of childbearing age. A Category D warning means that there is now human evidence of the risk of birth defects, as opposed to the Category C warning topiramate previously had, which was only supported by evidence in animal studies.

The FDA told the company that its Endocrine and Metabolic Advisory Committee will host a panel in the first quarter of 2012 to reassess the risks associated with the drug. A panel in July 2010 voted 10-6 against approval of the obesity drug.

This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

Vivus’s resubmission of the new drug application for its obesity drug Qnexa (topiramate/phentermine) is for a severely limited patient population – excluding all women under 55 years of age.

The price of the deal the company reached with the Food and Drug Administration in September on a plan for an early new drug application (NDA) resubmission was that it would have to restrict the patient population – excluding women of childbearing age to avoid the risk of birth defects in babies born to women taking the drug.

Chief Financial Officer Timothy Morris told "The Pink Sheet" that the restriction would mean the drug is off limits to any woman under the age of 55. By eliminating patients who could become pregnant, the company sidesteps the concerns about teratogenicity raised in the FDA’s "complete response" letter rejecting initial approval on Oct. 28, 2010.

While the company says that the drug can be used in some 80 million Americans, it will not be able to market the drug to a prime demographic.

Mr. Morris said there will be some exceptions; women under 55 will be able to get a prescription if their doctor believes they do not have childbearing potential.

And the company is looking ahead to expand the indication; Vivus is awaiting the results of FORTRESS, a post hoc analysis that will take a closer look at the effects of topiramate on women who bore children while taking the drug. The results are expected in December, and Vivus will submit top-line data to the FDA at that time.

According to the Oct. 17 NDA submission, Qnexa will be indicated for obese patients with a body mass index (BMI) over 30 kg/m² or overweight patients with a BMI over 27 who do not have childbearing potential, and who have at least one comorbidity, like high blood pressure, type 2 diabetes, or abdominal obesity.

On top of the original datasets, the filing adds 2-year data from the SEQUEL study – based on a 1-year extension of a subset of patients that completed the 56-week CONQUER study. The NDA also includes study results from a recent sleep apnea trial to help support the company’s claims that Qnexa does not contribute to heart disease or an elevated heart rate. The company is also studying the drug for sleep apnea and diabetes.

Vivus submitted a Risk Evaluation and Mitigation Strategy (REMS) as well. Mr. Morris would not comment on what the REMS included, but said that Vivus is waiting for feedback from the agency on its proposal.

Prior to last year’s action letter, Vivus had proposed a REMS plan that included a voluntary pregnancy registry, because 34 women in the Qnexa clinical trials became pregnant despite measures taken by the company to keep accidental pregnancies from occurring.

Qnexa is a combination of phentermine, an appetite suppressant, and topiramate, a form of Johnson & Johnson’s antiseizure medication Topamax. Both components are available as generics. In March, the FDA reclassified topiramate as Pregnancy Category D because of the drug’s potential to cause birth defects, usually cleft lip or palette. Warnings are now included on the labels of all forms of the drug, and doctors are instructed to evaluate whether the benefits are worth the risks when treating a woman of childbearing age. A Category D warning means that there is now human evidence of the risk of birth defects, as opposed to the Category C warning topiramate previously had, which was only supported by evidence in animal studies.

The FDA told the company that its Endocrine and Metabolic Advisory Committee will host a panel in the first quarter of 2012 to reassess the risks associated with the drug. A panel in July 2010 voted 10-6 against approval of the obesity drug.

This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.