Alkermes Schizophrenia Drug Heads To FDA, But Questions Linger

Xconomy Boston — 

Alkermes got some much-needed good news on Thursday, announcing that an experimental schizophrenia drug fared better than a staple drug for the debilitating disease in a closely watched study. But is that benefit big enough for doctors to prescribe the drug, if it’s approved, over cheap generics?

Alkermes (NYSE: ALKS), of Dublin, Ireland, and Waltham, MA, said that ALKS 3831 succeeded in the second of two Phase 3 studies. This study, dubbed Enlighten-2, was designed to test whether ALKS 3831 can lead to less weight gain than the schizophrenia drug olanzapine (Zyprexa). Weight gain is a common side effect of psychiatric drugs, including the generic olanzapine.

In the study, Alkermes enrolled 561 schizophrenia patients and gave them either ALKS 3831 or olanzapine for six months. Of those patients, 538 were given the medications and had their weight assessed at least once over the course of the study. The main goals of the trial were for ALKS 3831 to lead to less of a jump in body weight than olanzapine over six months, and for fewer patients on the Alkermes drug to gain at least 10 percent more weight from the start of the study.

Alkermes said ALKS 3831 succeeded on both measures, as well as a secondary goal evaluating the proportion of patients who gained 7 percent or more weight during treatment.

Specifically, the 272 patients on olanzapine had an average 6.59 percent weight gain after six months, compared to a 4.21 percent weight gain for the 266 patients on ALKS 3831. Some 29.8 percent of olanzapine patients had at least a 10 percent weight gain during the study, compared to 17.8 percent of those on ALKS 3831. And 42.7 percent of olanzapine patients had at least a 7 percent weight gain, versus 27.5 percent of those treated with ALKS 3831.

The most common side effects associated with the Alkermes drug were drowsiness, dizziness—and weight gain. Alkermes said 3.6 percent of patients on ALKS 3831, however, suffered an unspecified serious side effect, compared to 2.5 percent of olanzapine patients.

Alkermes said it aims to file for FDA approval of ALKS 3831 in mid-2019 based on the results. The company’s shares, which closed at $36.88 apiece yesterday, ticked down slightly to $36.50 apiece Thursday morning.

Alkermes started out as a drug delivery specialist but has since made a concerted effort to transform itself into a drugmaker. That effort suffered a stinging setback earlier this month when an FDA panel rejected its experimental depression drug ALKS 5461. But Alkermes still has ALKS 3831, which is now headed to the FDA.

The Alkermes schizophrenia drug is a combination of olanzapine and a second compound called samidorphan. It’s supposed to have the same antipsychotic benefits of olanzapine, but without the same type of weight gain.

That effect wasn’t seen in Alkermes’ first Phase 3 study, called Enlighten-1, however—people on both olanzapine and ALKS 3831 gained weight at similar rates. But Alkermes executives at the time pointed to the fact that the trial was only four weeks long and really meant to measure the drug’s effectiveness—it wasn’t a long enough study to draw conclusions about weight. The truer test of those effects is Enlighten-2, a study that lasted six months. Alkermes said in a prepared statement today that the weight gain trends for each drug “began to separate after week 4 and continued to diverge” for the rest of the study. Those on ALKS 3831 saw their weight stabilize after six weeks and stay stable for the rest of the trial, Alkermes said.

It remains to be seen, however, whether the benefits are substantial enough for ALKS 3831 to sell well in the real world. In a note to investors, Stifel analyst Paul Matteis noted that the drug importantly had a “solid benefit” on “weight gain outliers,” as in those whose weight jumps by at least 10 percent, a “major drawback of olanzapine in the real world.” But the difference versus olanzapine wasn’t as stark as in earlier testing, and patients on Alkermes’s drug still gained a decent amount of weight—possibly more than they might on other antipsychotics than olanzapine, Matteis wrote.

Alkermes will hold a conference call this morning to discuss the results. The company hasn’t given all the key details from the study, but noted that it would submit the results to a peer-reviewed journal and provide the full results at a future medical meeting.

Here’s more on Alkermes, its transformation, and ALKS 3831.