By Aaron Lorenzo
Staff Writer
Novartis Pharmaceuticals Corp. and Celgene Corp. on Thursday said the FDA approved a refined version of Ritalin to treat attention-deficit/hyperactivity disorder (ADHD).
The FDA granted marketing approval for Focalin (dexmethylphenidate HCl), which contains only the more active isomer responsible for effective management of the symptoms of ADHD, a neurobiological disorder that disrupts a persons ability to regulate behavior and maintain focus. East Hanover, N.J.-based Novartis manufactures Ritalin, but Warren, N.J.-based Celgene developed Focalin.
With half the dose, youve got, in the pivotal trial, the same efficacy of regular Ritalin, John Jackson, chairman and CEO of Celgene, told BioWorld Today. So its kind of a refined form of Ritalin, a purer form.
Novartis licensed worldwide (excluding Canada) marketing rights to the drug and all related intellectual property and patents from Celgene. Novartis will market Focalin in the U.S. In Canada, Celgene has an agreement with Biovail Corp. International, of Toronto.
Celgene will get royalties from Focalin, and from the entire line of Ritalin products, including the drugs first version. Celgene also will profit from another Ritalin derivative, Ritalin LA, which recently received an approvable letter from the FDA, Jackson said.
I think thats probably a first in the pharmaceutical industry, Jackson said of the extended royalty arrangement.
Specific financial terms were not divulged, but analysts estimate eventual sales of Focalin will be between $150 million and $300 million. Jackson said Celgenes royalty take will start relatively low and then end up after three or four years in the 25 [percent] to 30 percent range for the entire family of products. (See BioWorld Today, Aug. 23, 2001.)
Also, weve retained the potential rights to market the drug in oncology should we get a label claim with the FDA, Jackson added.
This is the second compound we have approved by the FDA, which differentiates us clearly from a lot of biotech firms, Jackson said. It will provide a differentiated cash flow stream to Celgene with no costs associated, which will help us further develop our very exciting pipeline.
Celgenes flagship product, Thalomid (thalidomide), is approved for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum. It also is being studied in numerous other indications.
The new Ritalin derivative, which originally was called Attenade, faced extensive testing before receiving approval.
Focalin underwent six clinical trials that included 684 ADHD patients, between the ages of 6 and 17, and 12 healthy adults. Two double-blind, placebo-controlled studies involving 221 patients between 6 and 17 demonstrated the drug to be effective in improving performance and behavioral symptoms of ADHD. Focalin was significantly more effective than placebo in lowering scores on a teacher rating scale (p<0.0001), signifying an improvement in the clinical status of the children. Parental assessments supported the teacher findings. In addition, Focalin significantly improved math test and Clinical Global Impression of Improvement scores.
In the label, there is no claim of superiority, Jackson said. In the trial, there was a significant p value showing that the single isomer lasts longer than the regular Ritalin. We only measured it up to six hours and it still had p value showing activity.
Overall, there was a low incidence of adverse events, with the majority being of mild severity. In double-blind, placebo-controlled trials there were no discontinuations due to adverse events. In long-term extension studies, only 7 percent of children and adults experienced an adverse event that resulted in discontinuation.
Like most drugs approved for the treatment of ADHD, Focalin is a schedule II drug.
We have since conducted a small pilot trial, and the abstract was published at the American Academy of Child and Adolescent Psychiatry in Hawaii last month, Jackson said. It was a small, open-label trial [that] was able to measure at eight hours and 10 hours, and was able to show a majority of patients actually get through the school day on a single dose. What we intend to do then, based on that pilot trial, is conduct another trial to see if, whether in a pivotal trial, we can get the longer activity and then make that part of the label claim.
The collaboration is not the only venture between the two companies. Novartis paired with Celgene to develop selective estrogen receptor modulator compounds for osteoporosis. (See BioWorld Today, Jan. 19, 2001, and April 27, 2000.)
[Novartis] paid us a $10 million up-front payment for that compound, Jackson said. And then there are further milestones, and if they bring the product to market successfully, we will get a low-double-digit royalty on that.
Celgenes stock (NASDAQ:CELG) closed unchanged Thursday at $36.99.