Drug Development

Roche flags first case of anti-drug antibodies that forced a patient to drop would-be blockbuster Hemlibra

Roche has raised a warning flag on Hemlibra, noting the first case where a hemophilia patient developed anti-drug antibodies that made the drug ineffective.

A media contact sent a statement to me that was originally circulated on Tuesday. In it, the company stated:

We recently learned that a patient in our phase III HAVEN 2 clinical trial developed a neutralising anti-drug antibody to Hemlibra. As with all therapeutic proteins, there is a potential for the development of anti-drug antibodies with Hemlibra, as indicated in the US and EU Hemlibra product labels. For this patient, the anti-drug antibody resulted in reduced efficacy of Hemlibra. The patient and his family have decided to discontinue treatment with Hemlibra, and he will resume treatment with his previous medicine. 

To date, more than 600 people with haemophilia A have been treated with Hemlibra worldwide, including in clinical trials. This is the first confirmed report of a detectable anti-drug antibody that has impacted the efficacy of Hemlibra in a person with haemophilia A. We continue to monitor for the development of anti-drug antibodies to Hemlibra in ongoing studies globally.

The development of anti-drug antibodies to Hemlibra is distinct from the development of inhibitors to factor VIII. Anti-drug antibodies to Hemlibra may affect whether the medicine works, but they do not change the severity of the underlying disorder. On the other hand, for the nearly one in five people with haemophilia A who develop inhibitors to factor VIII , the inhibitors not only affect the efficacy of factor VIII replacement therapies, but they can also affect any natural factor VIII in the body. Inhibitors to factor VIII put people with haemophilia A at greater risk for life-threatening bleeds or repeated bleeds that can cause long-term joint damage. 

Patient groups — as well as market rivals — have been paying close attention to this drug as it begins its global rollout. A few weeks ago organizations in the US and Europe were quick to pick up and post an update from Roche noting the 5 deaths that have been recorded among patients taking the drug, adding that none of the deaths — including 2 recent deaths — had been directly linked to their drug.

According to a spokesperson, 2 deaths were recorded recently which physicians linked to a pre-existing condition in one case and major vascular surgery in another. Those cases followed deaths associated with a rectal hemorrhage and 2 intracranial hemorrhages, which initially stirred early concerns about the drug.

Roche has blockbuster ambitions for Hemlibra, which poses a major threat to aging franchises at Shire — now being courted by Takeda with a $65 billion buyout agreement in place. Analysts have pegged potential peak sales at up to $5 billion, making this drug hugely important to Roche as it deals with the loss of its three big franchise biologics.

Regulators have been helpful moving this one along, approving the therapy for patients with factor VIII inhibitors. Just days ago the FDA added a breakthrough designation for the drug for use among patients without factor VIII inhibitors, pointing the way to an even bigger market.

The critical focus here is on getting patients who have been stable on Shire’s factor replacement therapy Advate to switch to the new med. But as with any new drug, stable patients may spend a considerable amount of time weighing the arguments for or against the therapy. Roche recorded revenue of 23 million Swiss francs for the drug in Q1, saying they were pleased by the early traction they were gaining.

Image: ROCHE

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Sr. Manager, Regulatory Affairs, CMC
CytomX Therapeutics San Francisco, CA
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Catalytic Data Science Charleston, SC
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Flatiron Health New York City or San Francisco

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