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Alzheimer’s drug study missed the primary endpoint; PR release touts benefits anyway

Phase 3 analyses in Alzheimer's show clinical benefit of tramiprosate in APOE4 carriers

Our Review Summary

Pill for Alzheimer'sThis news release from a public relations firm on behalf of drug manufacturer, Alzheon, describes an experimental compound tramiprosate that showed some impact on patients carrying the APOE4 gene which is present in many people who go on to develop Alzheimer’s disease. The drug is thought to target amyloid — protein fragments that aggregate abnormally in the brains of people with Alzheimer’s. But the dense technical language of the release prevents most readers from understanding the scale of the improvement reported in patient thinking or behavior during this study.

The major drawback of the release is that it didn’t talk about limitations of the sub-group analysis. While exploratory, this sub-group analysis cannot lead one to draw any conclusions about whether the drug “worked,” given that the overall study was negative.

The release also did not help readers understand when the drug would be prescribed, in relation to diagnosis, if the drug is approved.

 

Why This Matters

Estimates are that more than 5 million Americans have Alzheimer’s disease, a progressive and disabling neurological disorder. This release about a drug that might slow decline or ease symptoms is disappointing. It claims the drug works, but doesn’t make it clear for readers just how well. We aren’t given context for understanding the numbers that are shared. Many caregivers are suffering emotionally and financially by the burdens of caring for a patient with this disease and eager to hear any good news about therapy.

Bottom line: This release on an experimental drug treatment trial for Alzheimer’s disease focused on a small sub-group analysis from which conclusions can’t be drawn.

Criteria

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

Not Satisfactory

This release is about clinical research on a compound that is not available yet to patients outside of an experimental setting. Even so, we wish the release had some cost context on the drug. When (or if) it debuts in the future, what might it cost?

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

Not Satisfactory

The release states that there is a “meaningful clinical benefit” to the study medication, known as tramiprosate.

But we couldn’t find a meaningful description of the benefit in clear language. What we did find was a densely technical section where effects were described as follows:

“The effects on the ADAS-cog cognitive outcome were significant at Week 65 (LS means difference from placebo: 3.47, nominal p = 0.007) and Week 78 (2.60, nominal p = 0.043), and corresponded to 66 percent and 40 percent benefit from tramiprosate compared to placebo. These effects were supported by functional benefits on the CDR-SB that showed a positive trend at Week 65 (LS means difference from placebo: 0.79, nominal p = 0.063) and were numerically in favor of tramiprosate at Week 78 (0.54, nominal p = 0.21).”

But even if the p values here were significant, this analysis would not mean the drug showed benefits.

The study itself — not the release — contains some helpful context on the sub-group analysis that might have improved the release.

“Drug effects in AD trials are considered clinically meaningful if they provide at least 25% benefit over placebo. The cognitive effect of the 150 mg BID dose in APOE4/4 AD patients corresponds to 40% benefit over placebo at week 78, and is thus clinically meaningful. This cognitive effect is also supported by positive trends on global function, which corresponds to 25% benefit on CDR-SB at the week 78 endpoint, as well as a numerically consistent effect on disability with 25% benefit on DAD. “

A news release is intended to communicate with a non-technical audience of news professionals but this release fell short of translating the science well. We would have liked some discussion of how the “cognitive effect” is measured in these patients. What exactly is a positive trend in global function? Some examples could have helped.

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

Satisfactory

The release contained enough detail about safety issues to give it a satisfactory when it noted: “The safety profile of tramiprosate in 2,025 AD patients across the two studies was favorable and similar in the APOE4 carriers and non-carriers. The main adverse events were gastrointestinal (nausea, vomiting and weight loss), which were mild or moderate in severity.”

We would have liked more discussion of how patients might use the drug and whether there are any other harms that could loom from treatment.

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

Not Satisfactory

The release didn’t mention the sizeable limitations of the study. The published study itself states that the research — based on a 2,000 patient cohort — did “not reach its primary objectives.” The evidence of efficacy was for a subgroup of patients who have specific genetic characteristics — and that sample size was limited. According to the published paper, “These findings require confirmation in prospectively defined studies in the APOE4/4 homozygous population.”

None of this made it into the news release.

Does the news release commit disease-mongering?

Satisfactory

There was no disease mongering.

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

Satisfactory

The release is clearly labeled as written on behalf of Alzheon, the manufacturer of the compound. The release further identifies the sources quoted as either employees of Alzheon or as investigators at one of the study’s research sites.

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

Not Applicable

This release summarizing the research study did not include comparisons with existing drugs — but we won’t fault them for that. There are no known therapies that “treat” Alzheimer’s, only those that relieve some of its underlying symptoms.

But a  mention of preventative strategies would have been welcomed here.

Many researchers are pointing out that Alzheimer’s is not a disease simply due to overload of amyloid but its causes may be multifactorial, with, for example, blood vessel disease (narrowing of small arteries) and high blood pressure being significant risk factors. Lifestyle changes, including regular exercise, may do more to help prevent Alzheimer’s than any drug now available, and a discussion of that is included in a HealthNewsReview.org blog post from earlier this year.

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

Satisfactory

The release states the drug is in on-going trials and one can infer the drug is not and will not be available in the foreseeable future. It describes next steps: “We are preparing to advance ALZ-801, a promising new treatment for Alzheimer’s disease, into confirmatory clinical studies in 2017.”

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

Not Satisfactory

The release states that this is the first time a correlation has been seen between an Alzheimer’s drug and the genetic status of the patient, where the dose appears to show the most effect in patients with two alleles for APOE4.

However, since the overall analysis did not show a benefit, the author’s claims are questionable. And there are many, many drugs being developed targeting amyloid, which an increasing number of researchers regard as folly.

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

Satisfactory

There is no unjustifiable language outside of the claims already critiqued under the Benefits and Novelty criteria.

Total Score: 5 of 9 Satisfactory

Comments (1)

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Linda Furlini

November 1, 2016 at 9:46 am

Cognitive benefits and improvement in global function as stated in the study are very vague and the time period the drug was tested is very limited. Generally, the disease develops very slowly does not follow a linear progression and symptoms can vary from day to day and moment to moment. As stated, the amyloid hypothesis is controversial. The types of improvements that make a meaningful clinical benefit to people with AD are not specified, which is similar to the promotion found of Alzheimer drugs currently on the market.

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