According to Vivus Inc, their experimental drug Qnexa for treating obesity showed positive results in late stage trials, where patients who took the new diet pill, a combination of phentermine (a stimulant) and topiramate (an anticonvulsant), shed an average of nearly 15 per cent of their body weight over a year and also showed significant improvements in cardiovascular and other obesity-related risk factors.

Vivus Inc announced results of the EQUIP and CONQUER Phase 3 trials in a public statement on Wednesday, 9 September. The 56-week pivotal studies evaluated the safety and efficacy of Qnexa in more than 3,750 patients in 93 centres.

According to the drug company, the studies:

“Met all primary endpoints by demonstrating statistically significant weight loss with all three doses of Qnexa, as compared to placebo.”

“Patients taking Qnexa also achieved significant improvements in cardiovascular and metabolic risk factors including blood pressure, lipid levels, and type 2 diabetes,” said the statement.

The key results showed that:

  • On average, in the EQUIP study, patients treated with Qnexa lost 14.7 per cent of their body weight (an average of 37 lbs or 16.8 kg) over the 56 weeks of the study.

  • Patients treated with Qnexa showed significant improvements in cardiovascular, metabolic and inflammatory risk factors.

  • The drug exceeded FDA efficacy benchmarks for weight loss agents at all three doses tested in the trials.

  • Completion rates were significantly higher than placebo at all three doses (up to 69 per cent), indicating the drug was well tolerated.

  • The drug showed a favourable safety profile (the balance between benefits and risk).

EQUIP Study

For the randomized, double-blind, placebo-controlled EQUIP study, the investigators recruited 1,267 obese patients from 93 centers across the US (1,050 women and 217 men) with a starting average BMI of 42.1 kg/m2 and weight of 256 lbs (116 kg). The trial lasted 56 weeks, comprising four weeks of dose titration and then 52 weeks of treatment.

The study had 3 arms: low dose Qnexa, full dose Qnexa, and placebo, and patients were asked to follow a low calorie diet that left them short of around 500 calories a day. They were also required to make some simple changes to their lifestyle.

The EQUIP study results showed that:

  • The average weight loss for patients taking Qnexa who completed the study was 37 pounds (16.8 kg) for the full dose group and 18 pounds (8.2 kg) for the low dose group, compared to 6 pounds (2.7 kg) in the placebo group.

  • 60 per cent of the patients on the full dose who completed the study lost at least 10 per cent of their starting body weight, while 43 per cent lost at least 15 per cent.

  • Completion rates were 47, 57 and 59 per cent for the placebo, low dose and full dose groups.

  • Full dose patients showed significant improvements in blood pressure, triglycerides and cholesterol.

CONQUER Study

The CONQUER study was a randomized, double-blind, placebo-controlled, prospective trial, that like the EQUIP study had 3 arms, except that the patients took either a once a day mid-dose of Qnexa (as oppoosed to a low dose), a full dose or placebo.

From across 93 centers in the US, the trial investigators recruited 2,487 overweight and obese patients (1,737 women and 750 men) who had high blood pressure, high cholesterol or type 2 diabetes and whose average starting BMI was 36.6 kg/m2 and weight was 227 lbs (103.0 kg).

As in EQUIP, the patients underwent 4 weeks of dose titration period followed by 52 weeks of treatment, were asked to follow a low calorie diet with a daily deficit of 500 calories a day and were required to make some simple changes to their lifestyle.

The CONQUER study results showed that:

  • The average weight of those who completed the study was 30 pounds (13.6 kg) in the full dose group, 24 pounds (10.9 kg) in the mid-dose group, and 6 pounds (2.7 kg) in the placebo group.

  • 64 per cent of the full dose patients who completed the study lost at least 10 per cent of their starting weight, while 39 per cent lost at least 15 per cent.

  • Completion rates were 57, 69 and 64 per cent for the placebo, mid dose and full dose groups

The CONQUER study results also showed a number of risk factor reductions in patients taking Qnexa compared to those taking placebo. The following results were reported for reductions among patients showing the highest levels at baseline for each risk factor (top 25th percentile) and who completed the 56 weeks of the study:

  • The patients with highest blood pressure experienced a significant systolic blood pressure reduction of 20 mmHg from 147 mmHg, compared to 14 mmHg in the placebo group.

  • There was also a significant reduction in blood pressure medication among the Qnexa patients compared to the placebo group.

  • The patients with the highest triglyceride levels experienced a significant reduction of 98 mg/dL from 268 mg/dL, compared to 42 mg/dL from 262 mg/dL in the placebo group.

  • The patients with the highest hemoglobin A1c levels (a measure of blood sugar for diabetes patients) experienced a significant reduction of 0.6 from 7.3 per cent compared to only 0.1 from 7.4 per cent for the placebo group.

  • There was also a significant reduction in diabetes medication among the Qnexa patients compared to the placebo group (all patients were treated to standard of care for type 2 diabetes).

Adverse Events

Across both studies the most commonly reported side effects were dry mouth, tingling, constipation, altered taste and insomnia. Using tests that followed FDA guidelines, the investigators found no signals for suicide risk. There were no suicide attempts or behaviours, and there was no sign that people were thinking of suicide across all treatment groups, said the company statement.

Overall scores for depression and quality of life, including self esteem and general health showed significant improvement among patients who took Qnexa.

Scores for depression or depressed mood adverse events were similar in Qnexa and placebo groups and under 2 per cent for moderate to severe events.

Leland Wilson, president and chief executive officer of VIVUS said:

“The outstanding results from the EQUIP and CONQUER studies, in addition to the results from EQUATE that were reported late last year, confirm the positive effect of Qnexa and underscore the important role this therapy may play in the lives of patients battling obesity and related co-morbidities, if approved by the FDA.”

He said the company plans to file for federal approval by the end of this year and also submit the study reports for peer-reviewed journal publication.

“We believe these results may provide a compelling opportunity for global pharmaceutical companies, and we intend to initiate partnering discussions now that we have the full data set in hand,” said Wilson.

However while these results are impressive, according to various reactions in the media this week, there remains the question of what might happen in the longer term, both for patients who continue to use the drug and those who come off it.

In the 1990s the “fen-phen” combination of fenfluramine and phentermine also achieved impressive results with weight loss, but it was eventually withdrawn after reported links with pulmonary hypertension and serious heart valve problems, followed by lawsuits that are still being pursued against the drug maker.

For Qnexa Vivus have combined phentermine with topiramate which is better known as an anti-epilepsy drug although several studies have recently reported it has shown positive results in controlling weight loss and binge eating, according to a comment by Dr Mitchell Roslin, of Lenox Hill Hospital in New York City, reported by MedPage Today.

Source: Vivus Inc, MedPage Today.

Written by: Catharine Paddock, PhD