Late last year, Sanofi ($SNY) and its development team at Genzyme were dealt a stinging slap-down on the MS drug Lemtrada, first by an expert panel and then by officials at the FDA who formally rejected their marketing application. After confidently predicting that they were on a straight track to an approval and a market worth hundreds of millions of dollars in annual sales, the embarrassing setback left a mark on the company's R&D rep that wasn't helped by the flurry of lawsuits that followed from angry investors who claimed to have been duped by the pharma giant.
Sanofi, though, never accepted the FDA's verdict, which raised some troubling questions about its $20 billion buyout of Genzyme. Initially company execs pondered an appeal, with only small chances of success, then recently decided to change course and try again--offering fresh analysis from its Phase III studies to try and get regulators to change their minds in a resubmission. A new Phase III study as demanded by the FDA, CEO Chris Viehbacher said publicly, was out of the question. And today the development team--prepping for a resubmission of its application in this quarter--is stepping up with results from a one-year extension study that tracked the progress of their MS patients enrolled in two pivotal studies.
Two years after patients in Phase III studies received their last course of treatment, many were still clearly benefiting from the drug, Sanofi investigators tell FierceBiotech this morning. The drug had durable responses on lesion volumes and the rate of brain atrophy--key points as Sanofi and Genzyme argue that the FDA got it wrong on Lemtrada.
The results demonstrate "durable remissions, long beyond their courses of treatment," says Mike Panzara, Genzyme's group vice president for MS, "matched by improvements in brain imaging measures. Those two courses of treatment led to a meaningful change in the disease course that is long lasting."
"This is an extremely competitive market," notes Bill Sibold, the head of MS at Genzyme. "In Lemtrada, with the efficacy we have seen - a long, durable effect - that has not been an option in the treatment regimen in MS." The drug potentially "changes the long-term prognosis of a chronic disease. It's new and exciting."
During the third year of follow-up in their extension study, Sanofi reports, "more than 70% of patients were free of MRI activity indicative of acute inflammation, defined as gd-enhancing or new or enlarging T2 hyperintense lesions." T2 lesion volumes--the combined burden of permanent brain injury and new lesion formation--did increase from year two to three but remained below pretreatment baseline. "The rate of atrophy, as measured by brain parenchymal fraction, already reduced after two years, continued to slow in the third year of follow-up and approximately 80 percent of patients treated with Lemtrada did not receive a third course of treatment in the first year of the extension."
There were also two deaths in the extension study--one from sepsis and another that was deemed accidental and unrelated. Aside from some common side effects like headaches and insomnia, investigators also noted that "autoimmune conditions (including immune thrombocytopenia, other cytopenias, glomerulonephritis and thyroid disease) and serious infections can occur in patients receiving Lemtrada."
This isn't the first time that Sanofi's investigators have touted the positive effects of Lemtrada. But regulators ripped up the company's application, harshly criticizing the trial results and in particular noting that "substantial" benefits would be needed to warrant the risk of this drug. And the risks, said the agency in a review, were severe.
"The certainty of the risks of potentially lifelong hypothyroidism, serious infusion reactions, melanoma and other malignancies, Graves's ophthalmopathy and other autoimmune disorders, and prolonged increased susceptibility to infection may not be balanced by the uncertainty that exists in the limited evidence of the potential clinical benefits from clinical trials that were not well-controlled," FDA drug reviewer John Marler wrote in an internal review last year.
Sanofi's response is that these adverse events can be tracked and reversed once they're spotted with an aggressive safety program following an approval. An approval now, Panzara and Sibold note, would give physicians and patients a chance to add Lemtrada to a list of new drugs to pick from, offering an alternative in treating a tough, debilitating disease.
Sanofi will find out later this year if it can finally make that argument stick at the FDA. It won't be an easy sell.
- here's the release