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FDA announces approval of new psoriasis drug with strong caveats on harms, but no data to support benefit claim

Rating

3 Star

FDA approves new psoriasis drug

Our Review Summary

The US Food and Drug Administration just approved a new drug to treat psoriasis, a common skin condition that can form thick, silvery scales and itchy, dry, red patches. Siliq (brodalumab) is mainly intended for patients who don’t respond to other forms of treatment, like anti-inflammatory topical medications and light therapies. The “last resort” recommendation may be due to the four completed suicides that took place during the clinical trial, leading the FDA to believe that Siliq may be correlated to an increased risk of suicidal ideation and behavior — especially in patients with a history of depression. As a result, the FDA is requiring Siliq to be sold with a “boxed warning” (the strictest warning put in the labeling of prescription drugs) and only through a restricted program.

The FDA news release devotes a significant chunk to the drug’s potential harms and makes clear who should or shouldn’t be taking Siliq. What’s mainly missing from the release are any numbers to give a sense of the scope of potential benefits and harms.  Regarding the drug’s potential benefits, the release uses only vague, comparative wording (“more patients… had skin that was clear or almost clear.”).  We don’t know how the participants were selected, how long they were followed up and how their improvement was assessed.

Furthermore, a clinical trial was stopped for a period of time due to safety concerns, which was then continued by another drug manufacturer. Although not explicitly stated, it is fair to assume that drug manufacturers also funded these clinical trials. These are study limitations that were never disclosed by the news release.

We did find a 90-page FDA briefing document online from 2016, which includes some efficacy data. Curiously, this document mentions five clinical trials instead of three. We’re not sure why the FDA release didn’t include the two other clinical trials that compared Siliq (brodalumab) to ustekinumab.

We also reviewed TIME.com’s coverage of this new drug.

 

Why This Matters

Specialty drugs treating skin conditions like psoriasis can be expensive. The main competitors to Valeant’s Siliq may be Novartis’ Cosentyx and Eli Lilly’s Taltz — both of which cost at least $16,600 for one dose. Although some of this could be covered by insurance, patients could still be responsible for co-pays, which could amount to thousands of dollars. In addition, if patients have exhausted all existing treatment options and are desperate to clear up their psoriasis, they may be willing to try riskier therapies. If there is a new alternative that is FDA-approved and cost-effective, then it certainly deserves to be reported — as in this case, with strong caveats.

Criteria

Does the news release adequately discuss the costs of the intervention?

Not Applicable

The FDA evaluates drugs without considering costs, which is why they are not discussed in this news release. We rate this one Not Applicable.

However, it looks like Siliq will end up being an expensive drug. Its main competitors could be Novartis’ Cosentyx and Eli Lilly’s Taltz — both of which cost thousands of dollars for a dose. A half dose of Cosentyx sells for over $8,300, while a half dose of Taltz costs over $13,600. Each drug then follows a different dosage pattern.

If companies can talk about a drug’s benefits, then it’s not too early to discuss what it may cost. We hope the FDA could one day also comment on the projected cost of a drug and its cost-effectiveness.

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?

Not Satisfactory

The news release does not give any numbers to describe the magnitude of benefit shown in the three clinical trials. All we know is that “more patients treated with Siliq compared to placebo had skin that was clear or almost clear.” But how many more patients and by how much? And how was this exactly assessed? The news release vaguely mentions a scoring system that looked at the “extent, nature and severity of psoriatic changes of the skin” without elaborating any further.

In a 2016 FDA briefing document online, there is some data related to the drug’s effectiveness, but the number of analyzed subjects falls short of the total 4,373 trial participants cited in the news release.

Without any numbers describing the benefit, we have no idea how effective Siliq really is, which is why we give the news release a Not Satisfactory rating here.

Does the news release adequately explain/quantify the harms of the intervention?

Satisfactory

We could have rated this release unsatisfactory on this criterion, since no numbers are given about the extent of the problems found in the trials. But we’ll give it the benefit of the doubt because of the extent of discussion on potential harms – despite the absence of numbers.

The release mentions that completed suicides occurred in patients treated with Siliq during clinical trials, which is why the drug’s label will include a boxed warning. Although the release states cause and effect hasn’t been established, some patients — especially those with a history of depression — seemed to show an increased risk for suicidal ideation and behavior.

The release uses language that may confuse readers about harms. In one place it says “A causal association between treatment with Siliq and increased risk of suicidal ideation and behavior has not been established” and in the next sentence claims that “Because of the observed risk of suicidal ideation and behavior, the labeling for Siliq includes a Black Boxed warning….”

Patients may also experience more infections, or allergic/autoimmune conditions, as Siliq targets the immune system. Other side effects associated with the drug include joint pain, headache, fatigue, diarrhea, throat pain, nausea, muscle pain, injection site reactions, influenza, low blood cell count and fungal infections, the news release adds.

Although we would have liked to have seen some numbers indicating how often these side effects occurred, and clarity about whether or not they were observed, we believe the news release does an adequate job addressing harms, as a significant chunk is devoted to this issue. This is why we give it a Satisfactory rating here.

Does the news release seem to grasp the quality of the evidence?

Not Satisfactory

There is too little discussion on the trials to assess the quality of evidence in the news release. We only know that there were “three randomized, placebo-controlled clinical trials with a total of 4,373 study participants with moderate-to-severe plaque psoriasis.” We don’t know who these participants were, how they were selected, how they were assessed for benefits and side effects, and long they were followed up.

We wish the FDA would point us to any published studies that were referenced in the approval process. According to the 2016 FDA briefing document online (page 71, fourth paragraph), clinical trials were abruptly stopped by the then drug manufacturer Amgen in May 2015, which meant participants did not take the drug past late June 2015. Studies resumed after AstraZeneca subsequently took over the drug’s development.

The reason for it being stopped was due to the four completed suicides that took place during the clinical trial. In addition, the FDA describes 11 individual suicide behavior and ideation events, and three deaths from unknown cause from October 8, 2010 through February 3, 2014. These participants were found to be on an active drug product and not on placebo (2016 FDA briefing document, page 18).

Curiously, the FDA briefing document mentions that five clinical trials took place altogether. Three compared Siliq to placebo, while the remaining two looked at Siliq compared to Ustekinumab (sold under the brand name Stelara).

Since many of these details were omitted, we give the news release a Not Satisfactory rating here.

Does the news release commit disease-mongering?

Satisfactory

There is no disease mongering in this news release. It provides some good, concise context on the skin condition and its symptoms.

Does the news release identify funding sources & disclose conflicts of interest?

Not Satisfactory

The news release does not disclose funding sources for the clinical trials. A 2016 FDA briefing document online (page 6, second paragraph) implies that the drug company funded the clinical trials to support its application for FDA approval.

Since none of this is mentioned, we give the news release a Not Satisfactory rating.

Does the news release compare the new approach with existing alternatives?

Satisfactory

Since Siliq is recommended as a last resort drug of sorts, the news release hints there are other alternatives available. These include other topical treatments like anti-inflammatory drugs, light therapy and oral/injected medications, such as immunosuppressants.

Although we would have liked more elaboration on other treatment options, we feel the news release did just enough for a Satisfactory rating here.

Does the news release establish the availability of the treatment/test/product/procedure?

Satisfactory

Since Siliq is a new psoriasis drug that just received FDA approval, it is clear that it is now coming onto the market. The news release states the drug will only be available through a restricted program called the Siliq Risk Evaluation and Mitigation Strategy. The release then lists the requirements of the program, which include patient counseling, signing of a patient-prescriber agreement form and pharmacy certification.

We feel this is good enough for a Satisfactory rating here.

Does the news release establish the true novelty of the approach?

Satisfactory

The news release makes it clear that this is a drug for patients who have not responded to other established methods of therapy. A FDA director comments that Siliq provides psoriasis patients with “another treatment option.”

We feel this is good enough for a Satisfactory rating.

Does the news release include unjustifiable, sensational language, including in the quotes of researchers?

Satisfactory

The news release does not include unjustifiable, sensational language.

Total Score: 6 of 9 Satisfactory

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