May 24, 2011 / 11:05 PM / 8 years ago

Deaths in Pfizer arthritis trial under microscope

* Safety of tofacitinib pill in spotlight at London meeting

* Drug’s efficacy “in same ballpark” as anti-TNF injections

By Ben Hirschler

LONDON, May 25 (Reuters) - Four deaths during a study of Pfizer’s (PFE.N) new rheumatoid arthritis pill will be pored over at a medical meeting in London this week, as doctors weigh the drug’s chances of upending current clinical practice.

Tofacitinib is Pfizer’s biggest pipeline hope and could become the first major new medicine to come from its own labs since Viagra more than a decade ago.

It has the potential to disrupt the rheumatoid arthritis market — currently dominated by multibillion-dollar injections — by offering patients a more convenient twice-daily tablet.

But the experimental drug’s prospects have been clouded by safety worries following news that four patients died after taking it in a late-stage Phase III study. [ID:nN21295734]

Joel Kremer of Albany Medical College, the primary investigator for the study, told Reuters that this number of deaths was not unusual, given the profile of patients involved.

Pfizer itself said last month that three of the deaths were determined by local investigators not to be study related, leaving just one case of a 58-year-old U.S. patient with respiratory infection linked to the drug.

But deciding causality is not easy.

Kremer said it seemed clear two of the other deaths — one due to brain trauma and one caused by heart failure in a Chinese patient with valvular disease — were not linked to tofacitinib, but the case of a 48-year-old Russian patient was less certain.

The Russian patient, on the lower 5 milligram dose of the drug, died 42 days after discontinuing treatment from a respiratory complication.

“It’s unlikely that two of the four were associated (with tofacitinib). It’s possible that the other two of the four were associated, but based upon the information I have it’s impossible to say with absolute certainty,” Kremer said.

Results of the study will be laid out at a news conference on Wednesday, ahead of presentation to the annual meeting of the European League Against Rheumatism (EULAR) on Friday.

Headline findings in March already declared the trial a success and Kremer said the drug’s effectiveness was “in the same ballpark” as injected biotech drugs, such as Abbott’s (ABT.N) $6.5 billion-a-year blockbuster Humira.

The 792-patient trial tested two doses of tofacitinib against placebo in people with rheumatoid arthritis who failed to respond to an existing disease modifying anti-rheumatic drug.

Significant and sustained responses were seen within a few weeks and, after six months, 58.3 percent of patients on the higher 10 mg dose had a 20 percent improvement in symptoms, such as swollen joints, pain and disability.


Georg Schett, head of rheumatology and immunology at the University of Erlangen-Nuremberg and a member of EULAR’s scientific committee, who was not involved in the research, said tofacitinib looked promising but safety was a critical factor.

“The key issue from this data is that safety has to be carefully monitored — also when the drug is approved,” he said in an interview.

“It’s clear that you have to be careful about a drop in white blood cell counts, which is usually mild but can lead to increased rates of infection, and also increased lipid levels.”

Infection risk and raised cholesterol — a potential problem for heart safety — are among the drug’s known side effects.

Pfizer hopes to capture a large chunk of the arthritis market with its so-called JAK inhibitor pill, which works by blocking signals from entering cells that would activate inflammatory responses.

Analysts, on average, have forecast annual tofacitinib sales of $1.1 billion by 2015, according to Thomson Reuters Pharma.

It should be filed for approval by the end of 2011 and Pfizer believes it has a healthy lead over rivals. “We are one phase ahead and that usually translates to about two years,” said Saeed Fatenejad, head of inflammation drug development.

Still, the U.S. drugmaker has its work cut out to displace successful injected drugs like Humira, Johnson & Johnson’s (JNJ.N) Remicade and Amgen’s (AMGN.O) Enbrel.

Meanwhile, other companies are chasing Pfizer with rival JAK inhibitors and AstraZeneca (AZN.L) also has another kind of oral arthritis drug in development called a SYK inhibitor.

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