It's been a rough year for Northstar Neuroscience (Seattle) from January when its lead stroke therapy failed in a clinical trial to July when a major shareholder pressured the company to either sell or liquidate — but perhaps the tide is about to turn.
Northstar said the FDA has granted conditional approval of a second clinical study of its Renova cortical stimulation system for the treatment of major depressive disorder. With this approval, the company said it expects to begin enrolling patients into its PROSPECT II study this quarter, with preliminary results anticipated during the second half of 2009.
The approval comes less than three months after Northstar said it would move away from stroke rehabilitation therapy and instead focus on its cortical stimulation for depression, putting all other clinical programs on hold (Medical Device Daily, Aug. 4, 2008).
The PROSPECT II study is a prospective, double-blinded, sham-controlled study designed to build on the positive safety profile and promising efficacy observed in the PROSPECT I feasibility trial, Northstar said. The trial will be conducted at up to six sites and will include up to 24 subjects.
"Major depressive disorder affects millions of people who are not adequately treated today and who suffer greatly. Targeted stimulation of the cerebral cortex has shown promise in relieving depressive symptoms where drugs and other therapies have not been effective," said John Bowers, president/CEO of Northstar. "This is an important milestone for our depression program, and we are excited to move forward with our clinical collaborators to begin study enrollment."
Cortical stimulation involves a neurosurgical procedure to place an electrode which Bowers describes as a flat and flexible device "a little bigger than a postage stamp" over the outermost layer of the brain, called the cerebral cortex. The electrode is then connected via a lead wire to a neurostimulator in the patient's chest. The pacemaker-sized neurostimulator and lead wire are implanted under the skin and are capable of continuously delivering electrical stimulation to the brain, Northstar said.
"The objective is to be able to provide very precise targeted stimulation and be able to provide stimulation on a continual basis," Bowers told Medical Device Daily.
Bowers said Northstar is targeting the area of the brain that regulates things like feelings and decision-making. In the brains of people suffering from severe, intractable depression, he said, the activities that are frequently seen in that area is different from the activities seen in the same area of a healthy person's brain.
"We're looking to intervene in a really targeted way to that area of the brain to affect neuroactivity," Bowers said.
In August, when the company reported that it was dropping its clinical work on stroke to focus on depression, Bowers told analysts during a conference call that the company had conducted a "thorough evaluation" of its clinical opportunities and that "based on our findings, we determined that increasing focus on our existing depression program and putting our other clinical programs on hold is the best course to achieving a viable therapy for the millions of patients suffering from treatment resistant depression, while also conserving our financial assets and striving to enhance overall shareholder value."
In July Northstar turned down an unsolicited takeover bid from Tang Capital Partners (San Francisco) that valued the company at $58 million (MDD, July 7, 2008). Then, RA Capital Biotech Fund (Boston), in a letter, asked Northstar either to find a buyer or make a cash distribution (MDD, July 16, 2008).
The company's value fell after its lead therapy — which sought to stimulate the brain to improve motion in stroke survivors — failed in a clinical trial in January.
Bowers told MDD that the "huge clinical need" for a new depression therapy makes it an important area of focus, and he noted results from the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study, funded by the National Institute of Mental Health, which found that 33% of all depressed patients do not have satisfactory sustained responses after four antidepressant treatments. The STAR*D trial, which evaluated more than 4,000 depressed patients, is known as the largest clinical study for depression ever conducted in the U.S.
"Cortical stimulation represents a new approach to treat depression," said Brian Kopell, MD, Northstar's VP of medical affairs. "Increasing evidence points to disordered neural networks in the brain as an underlying cause of depressive symptoms. We believe that we can influence these networks with electrical stimulation without placing electrodes deep within brain tissue. This technology has the potential to offer an alternative treatment to many desperate individuals who currently have exhausted conventional options for the treatment of major depressive disorder."
According to Northstar, nearly 15 million American adults suffer from major depressive disorder, which is defined as a serious medical illness that goes beyond "the blues."
While there are a variety of antidepressant medications that can treat depression, these drugs often don't work either because of side effects such as weight gain or sexual dysfunction — or intolerability. Another option for depression treatment is electroconvulsive therapy (ECT), but Northstar says about 20% to 50% of patients who respond to ECT relapse within six months.
Another treatment option that just became available last week from a private company, Neuronetics (Malvern, Pennsylvania) is a device that uses transcranial magnetic stimulation (TMS) to treat major depressive disorder when antidepressant medication fails to work. Neuronetics said last week that the FDA has cleared its NeuroStar TMS system for the treatment of depression (MDD, Oct. 9, 2008).
The obvious difference between the two therapies is that one involves a series of 40-minute treatment sessions in a psychiatrist's office in which the doctor uses a coil to deliver magnetic pulses to the patient's brain, while the other involves a permanently implanted brain "pacemaker."
Another less-obvious difference between Northstar's depression program and the magnetic stimulation therapy from Neuronetics is the patient population. The NeuroStar device is available to patients who have failed to achieve satisfactory improvement from one prior antidepressant medication or above at or above the minimal effective dose and duration in the current episode. The inclusion criteria for Northstar's PROSPECT II trial are even more selective.
"To be included in this study, patients need to have failed four previous therapies," Bowers said.