Slow Sales Uptake For Brintellix Show The Challenges Facing New Depression Drugs
R&D efforts on the part of major biopharmaceutical companies for novel drugs to treat depression and other CNS diseases have eroded over the past decade. In fact, a study published by the Rand Corporation referred to these as “neglected diseases”, a jarring comment when one considers how widespread these diseases are and that current treatments, while adequate, are less than optimal. Take, for example, depression. The selective serotonin reuptake inhibitors (SSRIs), such as Pfizer PFE +1.15%’s Zoloft (generic name, sertraline) and GSK’s Paxil (paroxetine), despite having been used for decades are less than perfect. They take weeks to become effective, have a variety of side-effects, and only work in about half of patients with depression. Certainly, there’s a need for new antidepressants that alleviate some, if not all of these issues.
While the big companies have exited this therapeutic area, the Danish company, Lundbeck, has stayed the course. In fact, in September of 2013, it received FDA approval for its novel antidepressant, Brintellix (vortioxetine). Brintellix is described by Lundbeck as a “novel multimodal antidepressant which offers the possibility to target several neurotransmitter systems with a single molecule.” Lundbeck conducted a robust clinical development program of more than 30 studies for this novel agent including eight phase 3 trials in depression, six of which were positive – a great result given the difficulty in showing statistically significant positive results in an area known for high placebo effects.
Beyond these studies, Lundbeck also sponsored REVIVE, a randomized clinical trial of Brintellix versus agomelatine in patients suffering with major depression (MDD). The key to REVIVE was that these patients had already failed to respond to first-line SSRIs. Brintellix out-performed agomelatine and was better tolerated as well. Brintellix was in a position to be used in patients with MDD who had failed on Zoloft or Paxil.
In order to help get the drug off to a good start, Lundbeck entered into a co-promotional deal with Takeda. In addition, in August of 2013, they hired 200 new sales reps to promote Brintellix. Lundbeck had prepared well both in positioning the drug and in putting significant resources behind it. In fact, people predicted good things for this novel antidepressant. EvaluatePharma predicted world-wide 2014 sales of $271 million and $1.435 billion in 2018. Deutsche Bank also was bullish with estimated 2019 sales of $1.85 billion.
However, Brintellix is off to a slow commercial start. Full year sales for this drug, launched in the U.S. and 11 other countries in 2014, amounted to $28.4 million (188DKK) only 10% of early predictions. First quarter sales for 2015 were $14.8 million (DKK), only a modest gain over the $12.5 million in sales for the fourth quarter of 2014. Admittedly, these are early days in the patented life of this drug. It has only been on the U.S. market for 18 months and less than a year in most other countries. But the sales to date have not been inspiring.
Why has Brintellix gotten off to such a slow start? One clue can be found in the first review it received from NICE , the National Institute for Health and Care Excellence in the U.K. Here is its guidance for Brintellix (vortioxetine):
The Committee acknowledged that having more treatment options was important for patients, and that vortioxetine may be beneficial for some people with a major depressive episode after initial treatment in primary care with a generic selective serotonin reuptake inhibitor (SSRI). However, the Committee concluded that there was no convincing evidence to show that vortioxetine was any more or less effective than other antidepressants. They also felt that the company had not sufficiently defined how vortioxetine would be used in the NHS, or reflected its potential position, within its economic model.
The committee was therefore minded not to recommend vortioxetine for treating adults with major depressive episodes after SSRI therapy and has requested further clarification and analyses from the company to address the issues it identified before it can decide whether vortioxetine is a cost-effective use of NHS resources.
Perhaps that’s the issue. Most payers are reluctant to reimburse for a new drug unless all other choices have been tried and have failed. It’s likely in the U.S. and other countries that such resistance to Brintellix is occurring, resulting in the slow uptake. But despite the acknowledged need for new antidepressants and despite the development program carried out by Lundbeck to distinguish its drug, payers appear skeptical. In this environment, it’s easy to understand why many companies have exited R&D in this therapeutic area. Lundbeck did a lot of things right, but it faces a strong headwind in making this a commercial success.
Brintellix can still grow sales. Another clinical trial with Brintellix called CONNECT showed that it performed better than Lilly ’s Cymbalta (duloxetine) on various cognitive measures when the two drugs were compared to placebo. As a result, it will be the first antidepressant in Europe to improve cognitive function in patients with depression. This may prove to be the boost Brintellix needs in order to come close to the billion dollar sales originally projected for this drug. But, it’s going to take time. Once again, a drug is only as successful as the value it delivers – as viewed not just by patients and physicians, but by payers as well.
R&D efforts on the part of major biopharmaceutical companies for novel drugs to treat depression and other CNS diseases have eroded over the past decade. In fact, a study published by the Rand Corporation referred to these as “neglected diseases”, a jarring comment when one considers how widespread these diseases are and that current treatments, while adequate, are less than optimal. Take, for example, depression. The selective serotonin reuptake inhibitors (SSRIs), such as Pfizer PFE +1.15%’s Zoloft (generic name, sertraline) and GSK’s Paxil (paroxetine), despite having been used for decades are less than perfect. They take weeks to become effective, have a variety of side-effects, and only work in about half of patients with depression. Certainly, there’s a need for new antidepressants that alleviate some, if not all of these issues.
While the big companies have exited this therapeutic area, the Danish company, Lundbeck, has stayed the course. In fact, in September of 2013, it received FDA approval for its novel antidepressant, Brintellix (vortioxetine). Brintellix is described by Lundbeck as a “novel multimodal antidepressant which offers the possibility to target several neurotransmitter systems with a single molecule.” Lundbeck conducted a robust clinical development program of more than 30 studies for this novel agent including eight phase 3 trials in depression, six of which were positive – a great result given the difficulty in showing statistically significant positive results in an area known for high placebo effects.
Beyond these studies, Lundbeck also sponsored REVIVE, a randomized clinical trial of Brintellix versus agomelatine in patients suffering with major depression (MDD). The key to REVIVE was that these patients had already failed to respond to first-line SSRIs. Brintellix out-performed agomelatine and was better tolerated as well. Brintellix was in a position to be used in patients with MDD who had failed on Zoloft or Paxil.
In order to help get the drug off to a good start, Lundbeck entered into a co-promotional deal with Takeda. In addition, in August of 2013, they hired 200 new sales reps to promote Brintellix. Lundbeck had prepared well both in positioning the drug and in putting significant resources behind it. In fact, people predicted good things for this novel antidepressant. EvaluatePharma predicted world-wide 2014 sales of $271 million and $1.435 billion in 2018. Deutsche Bank also was bullish with estimated 2019 sales of $1.85 billion.
However, Brintellix is off to a slow commercial start. Full year sales for this drug, launched in the U.S. and 11 other countries in 2014, amounted to $28.4 million (188DKK) only 10% of early predictions. First quarter sales for 2015 were $14.8 million (DKK), only a modest gain over the $12.5 million in sales for the fourth quarter of 2014. Admittedly, these are early days in the patented life of this drug. It has only been on the U.S. market for 18 months and less than a year in most other countries. But the sales to date have not been inspiring.
Why has Brintellix gotten off to such a slow start? One clue can be found in the first review it received from NICE , the National Institute for Health and Care Excellence in the U.K. Here is its guidance for Brintellix (vortioxetine):
The Committee acknowledged that having more treatment options was important for patients, and that vortioxetine may be beneficial for some people with a major depressive episode after initial treatment in primary care with a generic selective serotonin reuptake inhibitor (SSRI). However, the Committee concluded that there was no convincing evidence to show that vortioxetine was any more or less effective than other antidepressants. They also felt that the company had not sufficiently defined how vortioxetine would be used in the NHS, or reflected its potential position, within its economic model.
The committee was therefore minded not to recommend vortioxetine for treating adults with major depressive episodes after SSRI therapy and has requested further clarification and analyses from the company to address the issues it identified before it can decide whether vortioxetine is a cost-effective use of NHS resources.
Perhaps that’s the issue. Most payers are reluctant to reimburse for a new drug unless all other choices have been tried and have failed. It’s likely in the U.S. and other countries that such resistance to Brintellix is occurring, resulting in the slow uptake. But despite the acknowledged need for new antidepressants and despite the development program carried out by Lundbeck to distinguish its drug, payers appear skeptical. In this environment, it’s easy to understand why many companies have exited R&D in this therapeutic area. Lundbeck did a lot of things right, but it faces a strong headwind in making this a commercial success.
Brintellix can still grow sales. Another clinical trial with Brintellix called CONNECT showed that it performed better than Lilly ’s Cymbalta (duloxetine) on various cognitive measures when the two drugs were compared to placebo. As a result, it will be the first antidepressant in Europe to improve cognitive function in patients with depression. This may prove to be the boost Brintellix needs in order to come close to the billion dollar sales originally projected for this drug. But, it’s going to take time. Once again, a drug is only as successful as the value it delivers – as viewed not just by patients and physicians, but by payers as well.