多発性硬化症の治療薬にフィンゴリモド (商品名ジレニア) という薬剤があります。治験に関わった医師には “FTY720” という方がしっくりくるかもしれません。FREEDOMS試験、TRANSFORM試験といった臨床試験で、有効性が示された薬剤です。

導入時に徐脈になったり、ヘルペスウイルス感染症が重篤化したり、白人でメラノーマが増えたりといった副作用は懸念されますが、自己注射が必要なインターフェロンと異なり経口薬というのが大きなウリです。

ところが、2013年7月30日の Reuter誌で、フィンゴリモドによると推測される進行性白質脳症 (PML) の症例が報道されてしまいました。

Patient taking Novartis MS pill developed rare disease

Tue Jul 30, 2013 5:18am EDT
* Patient took Novartis’ Gilenya MS pill

* Developed progressive viral disease

* First incidence in 71,000 patients

* Gilenya facing competition from Biogen’s Tecfidera

ZURICH, July 30 (Reuters) – A patient taking Novartis’ multiple sclerosis pill Gilenya developed a rare and potentially fatal viral disease, the Swiss drugmaker said on Tuesday, an unexpected setback as it faces growing competition from new oral treatments.

Gilenya is one of Novartis’ big new drug hopes, growing 66 percent in the second quarter to $468 million. But the drug faces competition from new medicines such as Biogen Idec’s Tecfidera.

Novartis said it had been informed of a case of progressive multifocal leukoencephalopathy (PML) in a patient who had been taking Gilenya for MS for seven months.

It said it was working with the reporting physician to understand all possible contributing factors, including those beyond treatment, given several atypical features of the case.

“The course of the underlying neurological disease was rapid with some atypical findings for MS on the MRI scans of the brain and spinal cord, as well as some unusual clinical features,” Novartis said in a statement.

Novartis said all previously reported cases of PML among the approximately 71,000 patients treated with Gilenya thus far had been attributed to prior treatment with Biogen Idec’s Tysabri, which bears a known risk of PML.

Deutsche bank analyst Tim Race said the case may provoke some concerns about Gilenya’s future growth potential. But he noted the incidence of reported PML cases for Gilenya has so far been extremely low.

“By the time there was a similar level of patient experience with Tysabri there had been 298 cases reported. Thus, even if the risk proves to be real it is likely to be of a very different order of magnitude,” Race said in a note.

販売元のノバルティス社は、これまでフィンゴリモド内服中に発症した PMLは全て、過去に使用されていた Natalizumab (タイサブリ) に起因するものだったとしています。しかし、今回の症例はフィンゴリモドが原因と認めざるを得ないようです。おそらく稀とはいえ、フィンゴリモドで PMLを発症することがあるとすれば、使用するハードルはこれまでより高くなりますね。記事では、患者が 7ヶ月間内服していたという情報以外書かれていないので、今後詳細な症例報告が出てくるのを待ちたいです。

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