Harmony Outcomes is positive for a drug already off the market

A study published October 2, 2018 in the Lancet found that albiglutide, a once-weekly injectable GLP-1 receptor agonist, reduced the combined risk of cardiovascular death, heart attack, and stroke by 22 percent compared with placebo in people with type 2 diabetes and existing cardiovascular disease.^[1] The finding is notable mainly because it arrived after GSK had already stopped selling the drug, known as Tanzeum in the United States and Eperzan in Europe.^[1][2]

The trial, called Harmony Outcomes, enrolled 9,463 adults age 40 and older across 610 sites in 28 countries between July 2015 and November 2016.^[1] Half received albiglutide, dosed at 30 to 50 milligrams based on blood sugar response and tolerability, and half received a placebo injection, both added to standard diabetes care.^[1] Patients were followed for a median of 1.6 years.^[1]

The primary combined outcome — cardiovascular death, heart attack, or stroke — occurred in 338 of 4,731 patients on albiglutide (7 percent, or 4.6 events per 100 patient-years) compared with 428 of 4,732 patients on placebo (9 percent, or 5.9 events per 100 patient-years).^[1] That works out to a hazard ratio of 0.78, with a 95 percent confidence interval of 0.68 to 0.90, a result researchers called statistically significant for both non-inferiority and superiority.^[1] Rates of acute pancreatitis, pancreatic cancer, and medullary thyroid carcinoma did not differ meaningfully between the two groups; no patients in either arm developed medullary thyroid carcinoma.^[1]

Despite the positive result, the drug's commercial fate had already been sealed. GSK had discontinued marketing Tanzeum in the United States before the trial results were published.^[1] In Europe, the European Commission formally withdrew Eperzan's marketing authorization on October 29, 2018, just weeks after the Lancet paper appeared, at GSK's own request and for what the company described as commercial reasons.^[2] Eperzan had first been authorized in the European Union on March 21, 2014, for treating type 2 diabetes.^[2]

Why it matters for patients

For anyone currently taking or considering a GLP-1 medicine, the Harmony Outcomes result underscores a broader point: several drugs in this class have now shown they can lower cardiovascular risk, not just blood sugar or weight, in people who already have heart disease.^[1] The study's authors argued that this evidence supports considering GLP-1 receptor agonists broadly as part of strategies to reduce cardiovascular events in type 2 diabetes.^[1]

But albiglutide itself is not an option. Patients in the US cannot get Tanzeum because GSK stopped selling it, and patients in Europe cannot get Eperzan because its authorization has been withdrawn.^[1][2] Anyone who was using albiglutide before it left the market would have needed to switch to an alternative GLP-1 drug or another diabetes treatment under a clinician's guidance. The episode is a reminder that a medicine's cardiovascular benefit in a large trial does not guarantee its continued availability, since companies can discontinue products for business reasons unrelated to trial outcomes.

What happens next

The European Commission's withdrawal of Eperzan's marketing authorization took effect October 29, 2018.^[2] The sources reviewed do not indicate any plan by GSK to relaunch albiglutide under a new brand or license it to another company. It is not yet known from available sources whether health authorities plan to reference the Harmony Outcomes data in guidance covering other GLP-1 drugs still on the market.