FDA Experts Back Brodalumab, With Warnings

| About: Valeant Pharmaceuticals (VRX)

After Amgen (NASDAQ:AMGN) and then AstraZeneca (NYSE:AZN) dropped the psoriasis project brodalumab because of suicide risks, it was surprising that any company was willing to pick it up, even though it had already been submitted to the US FDA. Leave it to 2015’s big risk-taker, Valeant (NYSE:VRX), to buy into this cheap, launch-ready asset.

Turns out brodalumab might not have been a terrible gamble, even as some of Valeant’s other Michael Pearson-era ventures have sputtered. Yesterday's positive advisory committee vote, with nobody voting against approval, improves the odds, though if the OK comes it seems certain that significant warnings will be slapped on brodalumab's label.

As a sign that regulators might be growing comfortable with the risk-benefit profile, earlier this month Japan approved brodalumab, with the local licensee Kyowa Hakko Kirin calling the IL-17 receptor antibody Lumicef.

Alert

The US regulator asked a three-way question on brodalumab’s approval: no, yes with suicide risk warnings restricted just to the label, or yes with additional mitigation beyond labeling, such as an enhanced communication strategy.

In the end, only four of the adcom’s 18 members voted for a risk-evaluation and mitigation strategy (REMS), and the remaining 14 voted for label warnings alone. The agency is not bound to the adcom vote and could impose a REMS, and in any case Valeant has proposed one.

The vote followed a presentation from regulators that discussed the suicides in patients who have taken brodalumab in clinical trials: four in psoriasis trials, one in rheumatoid arthritis and one in psoriatic arthritis. One of the self-inflicted deaths in the psoriasis trials was judged as “indeterminate” because of the presence of illicit drugs. Suicide ideation was noted in placebo and active comparator arms, but no completed suicides occurred.

However, the FDA staff also highlighted a greater rate of mental illness in psoriasis patients generally – a UK cohort study indicated that psoriasis patients were 44% more likely than non-psoriatic patients to have considered suicide. Thus, regulators acknowledged “uncertainty about whether the signal for completed suicide is a risk related to brodalumab treatment”.

“From the available data we cannot conclude whether or not suicide is a drug-related risk,” the briefing documents stated (All eyes on brodalumab fallout, May 26, 2015).

This raises the question of why first Amgen was eager to unwind a development deal with Astra for an agent that Amgen invented, and then Astra unloaded it for $100m up front and $345m in milestones (Baffling Valeant strikes for troubled Astra psoriasis project, September 1, 2015).

Nevertheless, this is now a project under the control of Valeant, which intends to call the antibody Siliq. The speciality pharma group must now think about performance with label warnings, a potential REMS, possible relegation to second-line use, and even contraindications in patients with a history of psychiatric disorders.

Third to market

This comes in the context of competition from new psoriasis biologicals, some of which will use the same mechanism of action. Novartis’ (NYSE:NVS) Cosentyx and Lilly’s (NYSE:LLY) Taltz have both been launched in the past 18 months, with the former having reported second-quarter 2016 sales of $260m, beating analysts’ forecasts by 23%.

IL-17 antibodies in psoriasis

Sales ($m)

Product

Company

2015

2016

2017

2018

2019

2020

2021

2022

Marketed

Cosentyx (secukinumab)

Novartis

261

665

1,035

1,344

1,747

2,144

2,530

2,915

Taltz (ixekizumab)

Eli Lilly

-

150

301

533

711

846

965

1,075

Approved

Lumicef (brodalumab)

Kyowa Hakko Kirin

-

2

8

14

20

27

33

38

Filed

brodalumab

Valeant

-

-

-

-

-

-

-

-

Click to enlarge
Click to enlarge

Cosentyx and Taltz, both IL-17 products, are on their way to blockbuster revenues, according to EvaluatePharma’s consensus of sellside analysts. These have warnings about infection and inflammatory risk and hypersensitivity similar to many injectable immunosuppressive drugs, but nothing about psychiatric risk.

In Japan Lumicef is reckoned to sell $38m a year by 2022. Valeant analysts, on the other hand, give no forecast for brodalumab – in Amgen’s hands, before the suicide news broke, this was forecast to sell $778m by 2020. That is an unachievable goal right now, although at the time of the Astra transaction Barclays analysts believed brodalumab would benefit from Valeant’s strong presence in dermatology.

This was, of course, before the revelations about Valeant’s aggressive sales and marketing practices came to light, something that is likely to keep launch forecasts in check. Brodalumab looks a safer bet for approval than it did a year ago, but commercial expectations should be modest.