After a tough couple of years things are finally looking up for Alkermes. The group should soon get US approval for its big pipeline hope, the antipsychotic ALKS 3831, if an advisory committee meeting held on Friday is anything to go by.
Making ALKS 3831 a commercial success looks like a trickier prospect. The sellside is forecasting sales of just $262m by 2026, according to EvaluatePharma consensus. Expectations vary widely, with Leerink pencilling in $300m peak sales versus Mizuho’s more bullish $700m, but both sets of analysts admit that the project could be tough to sell.
Alkermes, meanwhile, is confident about ALKS 3831’s commercial chances, although a spokesperson declined to give an estimate for peak sales. Before the panel meeting, Blair Jackson, the company’s senior vice-president of corporate planning, told Evaluate Vantage that the project, if approved, should “drive a lot of growth for the business”.
It is clear that the group, which two years ago saw the failure and ultimate FDA rejection of its depression project ALKS 5461, needs fresh blood. Sales of Alkermes’ marketed addiction drug, Vivitrol, have slowed, and its clinical pipeline looks thin.
|The outlook for Alkermes|
|Product/project||Description||Status||2026e sales ($m)|
|Vivitrol||Opioid antagonist for addiction||Marketed||519|
|Vumerity||Monomethyl fumarate prodrug for MS||Marketed||85*|
|ALKS 3831||Antipsychotic plus opioid antagonist||PDUFA Nov 15, 2020||262|
|ALKS 4230||IL-2 fusion protein for oncology||Phase II||33|
|*Royalties only, product licensed to Biogen.
At least ALKS 3831 now looks odds-on for approval in schizophrenia and bipolar disorder. The project is a combination of the antipsychotic olanzapine and the opioid antagonist samidorphan; the rationale is that the combo would be as effective as olanzapine while avoiding the weight gain that has been a problem with the older antipsychotic.
Here, ALKS 3831 was a qualified success – patients receiving the drug did gain weight, but not as much as those on olanzapine (Weighty issue shrinks for Alkermes, but does not disappear, November 29, 2018).
Still, on Friday the panellists voted 16-1 that samidorphan meaningfully mitigates olanzapine-associated weight gain.
The other big question around ALKS 3831 had been safety; specifically, issues with using an opioid antagonist in a psychiatric patient population in which the abuse of opioids is relatively high.
The FDA was concerned that samidorphan might spur withdrawal in patients who are physically dependent on opioids, or could lead to overdose in patients trying to overcome its opioid-blocking effects. There is also the risk that samidorphan might cancel out the painkilling effects of opioids when these are medically necessary.
These worries look unlikely to hold back approval of ALKS 3831: the panel voted 13-3 that the safety profile of ALKS 3831 has been adequately characterised. And Alkermes could also avoid a REMS programme, with the panel coming down 11-6 that labelling would be enough to mitigate the risks relating to samidorphan.
Although some panellists argued against approval in bipolar disorder, asking for more data, the path has largely been cleared for an FDA nod. However, getting to market might be the easy part.
Shifting patients from generic antipsychotics to a branded product could be tough, especially given ALKS 3831’s “decent [but] not stellar” weight-gain profile, to quote Stifel analysts. In a similar vein, Mizuho noted that patients would likely need to try multiple generic products before being given ALKS 3831.
Perhaps these concerns could help explain why, after gaining 13% in premarket trading, Alkermes’ share price was up just 2% soon after the open this morning.
Still, the group has little else to pick up the slack right now. Alkermes’ pipeline also features an IL-2-targeting project, ALKS 4230, which posted intriguing results at the recent Esmo meeting. But IL-2 has proven a tough nut to crack.
And even if the company succeeded here, it is not about to shift its focus to oncology any time soon, Mr Jackson told Vantage. Instead, the group will look to partner at least some of the ALKS 4230 programme, while remaining “heavily involved” in the asset’s development, he said.
Alkermes’ only other pipeline assets are the preclinical HDAC inhibitors gained via last year’s purchase of Rodin Therapeutics, which Alkermes reckons could have utility in neurodegenerative diseases as well as cancers.
But it is very early days for these projects. For the foreseeable future the company’s hopes rest on making a mark with ALKS 3831.