Novartis Drug Helps Broader Group of Rare-Disease Patients

(Bloomberg) -- Novartis AG's Zolgensma, a gene therapy under review for treating children with a rare inherited disease that typically kills before the age of 2, also appears promising for a broader group of patients where the condition slowly destroys motor function.

The results of three studies presented at the American Academy of Neurology's annual meeting in Philadelphia suggest the one-time use of Zolgensma halts the destruction of neurons caused by spinal muscular atrophy within weeks, creating an opportunity for more patients. Those with the gene mutation don't produce a protein critical for the survival of the motor neurons that carry instructions from the brain to the body's muscles.

Fewer than 500 children are born each year in the U.S. with the disease known as SMA, and 60 percent have the most severe form that means they will never crawl or walk. Novartis has filed for U.S. Food and Drug Administration approval to sell Zolgensma to treat these patients, with a decision expected at the end of the month. But it also appears effective in a milder form of the disease that develops in patients who have backup genes that help produce some of the missing protein. There are about 9,000 to 10,000 Americans living with the condition, said David Lennon, president of the Novartis unit that developed the therapy.

Normal Development

“For these children with type 2 SMA, their disease is less profound,” Olga Santiago, chief medical officer for Novartis' AveXis unit, said in an interview. “What we are observing here is that you are halting the progress of the disease at the time you intervene. There is no further motor neuron degeneration that occurs, and they continue to develop and gain the function you would expect based on normal childhood development.”

Shares of Switzerland's Novartis, which have climbed 12 percent so far this year, were little changed in Zurich on Monday, trading at 83.43 francs.

The first study involved 19 patients up to age 5 who were already showing symptoms of the disease. It found improvements in muscle strength in things like reaching, grabbing and touching, with three patients who were able to stand independently, including two who eventually walked, within six and a half months of treatment. Two patients had signs of liver damage.

Two More Studies

The second study was conducted in 18 infants who were diagnosed early, before they started showing any signs of the disease. All continued to develop normally, including four who were able to sit without support and one who could stand without help, something that never happens in untreated infants.

“Once motor neuron death occurs, it is irreversible, so we want to halt it before any motor neuron damage occurs,” Santiago told reporters on a conference call. “We have to diagnose them at the time of birth when they have the genetic defect detected, and then treat them early on before they manifest any symptoms. Here we are treating them in weeks instead of months. They are achieving the motor milestones, and they are actually doing it in an age-appropriate time frame for normal childhood development.”
The final study is intended to confirm the early promise seen in patients with the most severe form of the disease. Just one of the 20 infants enrolled died by age 10.5 months, from respiratory failure that wasn't related to the treatment, and one patient withdrew from the study. Normally half of children with the condition will have died by that age. The children continued to hit developmental milestones, including one who could crawl, one who could stand and 11 who could sit -- achievements that aren't reached by untreated patients.

Single Dose

“With just a single, one-time dose, we are seeing Zolgensma provide prolonged survival, rapid motor function improvement and milestone achievements that patients never experience if their disease is left untreated,” Lennon said.

The findings may set up a battle between Zolgensma and Biogen Inc.'s Spinraza, the only medicine currently approved to treat spinal muscular atrophy. Spinraza, which is is injected several times a year into patients to treat the condition, generated $518 million for Biogen in the first quarter, beating the $486.5 million analysts expected. It's unclear whether patients would benefit from getting both treatments, since they haven't been tested together.

“There is no scientific rationale and no clinical data to support combination therapy or use of Spinraza after gene therapy,” Lennon said. “So we would not be recommending that based on what we know today. ”

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

To contact the editors responsible for this story: Drew Armstrong at darmstrong17@bloomberg.net, Kevin Miller, Linus Chua

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