PML found in MS patient taking Ocrevus

[agate]

Since this person was on Tysabri previously, this news may need more details before any clear connection with Ocrevus is made.

Roche investigating case of patient illness after taking MS drug

May 24, 2017, 03:02:00 PM EDT By Only registered and activated users can see links., Click Here To Register...


ZURICH, May 24 (Reuters) - A person in Germany treated with Roche's ... new multiple sclerosis drug Ocrevus has been diagnosed with an often-deadly brain infection after switching from another medication earlier this year, the Swiss drugmaker said on Wednesday. Roche said it was investigating a case of Progressive Multifocal Leukoencephalopathy (PML) in a patient previously being treated for three years with Biogen Inc's Tysabri and who had received a single dose of Ocrevus in February.

Ocrevus was approved in the United States in March.

Roche said the case of the rare brain disease that is usually fatal or disabling was reported as a carry-over from Tysabri, also known as natalizumab, by the physician who had been treating the patient.

Biogen declined to make any immediate comment.

Ocrevus is an integral part of Roche's strategy to replace revenue from older blockbuster cancer medicines Rituxan, Avastin and Herceptin whose patents are expiring, leaving them increasingly exposed to cheaper copies, called biosimilars.

"Patient safety is Roche's highest priority and we are gathering more details about the case and the patient's history," Roche said. "We will continue to share information with healthcare providers and global health authorities as we know more."

The patient who developed PML had previously tested positive for John Cunningham virus, a common virus that is normally harmless but which can lead to the brain disease in MS patients who have weakened immune systems. Dozens of patients undergoing treatment with Tysabri have been diagnosed with PML.

Use of the drug was temporarily halted a decade ago, but resumed after patients for whom the medication was effective demanded its return and regulators added restrictions to its use.

Roche has said no PML cases emerged during its trials of Ocrevus, but the company included warnings to patients taking the medication that there was a risk they could get the disease.

(Reporting by John Miller; Editing by Edmund Blair, GregMahlich) ((J.Miller@thomsonreuters.com; +41 58 306 7734; ReutersMessaging: j.miller.thomsonreuters.com@reuters.net))


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[Virginia]

This will be interesting to follow.

[agate]

Roche said the case of the rare brain disease that is usually fatal or disabling was reported as a carry-over from Tysabri, also known as natalizumab, by the physician who had been treating the patient.

Biogen declined to make any immediate comment.

Reading between the lines here, does it sound as if Tysabri is going to get blamed for this PML case? Maybe correctly?

[Pegakafarmgirl]

Reading between the lines here, does it sound as if Tysabri is going to get blamed for this PML case? Maybe correctly?

That's the way I read it too

[agate]

It would be helpful to know how long this person waited between stopping Tysabri and starting Ocrevus.



It really sounds as if it's a Tysabri problem.

[Lazarus]

"Ocrevus is an integral part of Roche's strategy to replace revenue from older blockbuster cancer medicines Rituxan, Avastin and Herceptin whose patents are expiring, leaving them increasingly exposed to cheaper copies, called biosimilars."

The company has done a good job of muddying the waters so it was hard to follow the research. I am glad I am on rituxan and hope this patient's situation is a result of previous med taken. The "biosimilars" in the article really intrigued me. Bingo! There will be more coming down the road than I had been expecting.

[Sunshine]

They said dozens got PML from Tysabri. But isn't it over 100?

[agate]

711 confirmed PML cases in persons with MS taking Tysabri as of 3/6/17:

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I was struck by that "dozens" too--one of those terms that can mean many, many dozens....

[agate]

The patient stopped Tysabri in February, started Ocrevus in April--not a very long interval there?

From Multiple Sclerosis News Today, May 25, 2017:

PML Found in Ocrevus-treated Patient Who Had Used Tysabri for 3 Previous Years

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A multiple sclerosis (MS) patient treated in Germany with Ocrevus (Ocrelizumab) has developed the dreaded brain infection progressive multifocal leukoencephalopathy (PML). But it is not clear whether the recently approved Genentech/Roche-developed treatment is the cause.

The patient took the last dose of a three-year course of Tysabri (natalizumab) in February.Tysabri is a known trigger of PML — a severe brain infection caused by the John Cunningham (JC) virus, which leaves the majority of patients severely disabled or causes their death.

In April, the patient received one dose of Ocrevus as part of a German compassionate-use program. The person has not been otherwise identified.

According to Anthony Vaughn, international communications leader, multiple sclerosis, at Roche, the company is investigating the case. An email statement he gave to Multiple Sclerosis News Today said the patient tested positive for JC virus infection, but did not specify if the testing was performed before or after the Ocrevus infusion.

The patient’s treating physician has reported the PML case as a carry-over from Tysabri, according to the Roche statement.

An opportunistic microbe, the PML-causing JC virus is not harmful to people with an intact immune response, but many MS treatments are immunosuppressive. Several therapies that target T-cells have been linked to PML. Ocrevus does not directly act on T-cells, but its close cousin Rituxan (rituximab)— which like Ocrevus targets CD20 B-cells — has also been associated with this aggressive brain disease.

No patient developed PML during Ocrevus' extensive clinical trials. But this fact is no guarantee that the condition will not appear as more patients receive the treatment. PML is a rare complication, and was not discovered in Tysabri-treated patients until the drug gained market approval.


The prescription label of Ocrevus includes a note about a possible PML risk, but that warning is largely thought to be an FDA precaution. Tysabri’s label, in comparison, now includes a much stronger notice of risk, called a black-box warning.

Genentech and its parent company, Roche, have kept a close eye on this possibility, with several currently running clinical trials aiming to explore the long-term safety of Ocrevus.


“Patient safety is Roche’s highest priority and we are gathering more details about the case and the patient’s history. We will continue to share information with healthcare providers and global health authorities as we know more,” Roche said in its statement.

[Virginia]

In the talk that Dr. Vollmer gave that I listened to on here regarding Ocrevus, I believe he stated that there was not a waiting period between taking one of the other drugs and Ocrevus. I don't think he named Tysabri specifically, however it only seems logical to me that at least a 4 month period should be observed between tysabri and any other drug.

[agate]

I can't find a good recent reference just now but I've done a little digging, and it looks as if the experts are leaning toward recommending a very short or no washout period between Tysabri and a different MS drug because of the risk of breakthrough disease activity.

A couple of guidelines recommended a 3-month wait between Tysabri and Rituxan.

[Sunshine]

I love the statement from Roche on Medpage today about being committed to patient safety. If they were, wouldn't they have put the money into the Phase III trials for Rituxan instead of developing Ocrevus which has a worse side effect profile than Rituxan?

Convenient to blame this on Tysabri. While it may be true, I don't see how they can jump to that conclusion so quickly.

[SuzE-Q]

In the talk that Dr. Vollmer gave that I listened to on here regarding Ocrevus, I believe he stated that there was not a waiting period between taking one of the other drugs and Ocrevus. I don't think he named Tysabri specifically, however it only seems logical to me that at least a 4 month period should be observed between tysabri and any other drug.

Except for the risk that arises of developing IRIS, immune reconstitution inflammatory syndrome, after terminating Tysabri, etc. which doesn't sound fun and could lead to great disability and rapid progression.

[Frog42]

Sounds to me like none of them really know. Seems only a little better than a guess..

[Virginia]

Suze-Q, you mean it is like a re-bound effect?