West Coast Editor

Almost a year and a half after BioMS Medical Corp. said it would be talking with regulatory authorities about a pivotal trial of the multiple sclerosis drug MBP8298, the company said the first patients with secondary progressive disease have been enrolled in the Phase II/III study

The Edmonton, Alberta-based company's stock (TSE:MS) closed Wednesday at C$3.46 (US$2.85), down C2 cents.

BioMS said in the spring of 2003 that a subgroup of MS patients with codes for HLA-DR2 or HLA-DR4 genes showed particularly high benefit from the drug, a synthetic peptide containing MBP amino acids 85 to 96, which are attacked by B-cell antibodies and T cells in MS. (See BioWorld Today, May 27, 2003.)

"We think it will work in some other HLA types, as well, and we've built into this trial a Phase II exploratory trial to see which other ones might benefit," said Kevin Giese, president of BioMS.

In November 2003 the company submitted an application regarding pivotal trials with the lead product, which apparently "cleans up" B-cell antibodies and down-regulates production.

The two-year trial is expected to enroll up to 553 patients, to be given either MBP8298 or placebo intravenously every six months. The primary endpoint is a statistically and clinically significant rise in time to progression of the disease as measured by the Expanded Disability Status Scale in the responder group.

That group consists of those patients with the immune response genes, HLA-DR2 or HLA-DR4, who are believed to account for up to 75 percent of the MS patient population, BioMS said.

Andrea Witt, who co-authored a September report on MS for Decision Resources in Waltham, Mass., said there is a "wide variety of answers" to the question of patient population size, however.

Her firm estimates relapsing/remitting MS - which is characterized by an attack that goes away - makes up about 65 percent of the diagnosed population, with chronic progressive (which includes the secondary progressive and primary progressive forms) accounting for the remainder. Within the chronic progressive MS category, between 67 percent and 80 percent suffer from secondary progressive disease, the indication targeted by the BioMS drug.

"It's when patients become worse, so really you're looking at the same prevalence as relapsing/remitting," Witt said. "Every relapsing/remitting patient eventually becomes secondary progressive."

She told BioWorld Today the earlier trial results with MBP8298 "looked pretty good for this particular patient population, with the caveat that this was a small trial." She pointed to the risk of some "nasty side effects" such as anaphylactic shock, which is "rare, but it happens."

The field is crowded with drugs for relapsing/remitting disease. BioMS' news comes in the shadow of word from mighty Biogen Idec Inc., of Cambridge, Mass., that its Antegren, renamed Tysabri (natalizumab), cleared the FDA as a combination therapy and monotherapy for relapsing disease, and Biogen already was selling Avonex (interferon beta-1a), the current MS market leader. (See BioWorld Today, Nov. 29, 2004.)

There's also Copaxone (glatiramer acetate), from Teva Pharmaceutical Industries Ltd., of Jerusalem, and more drugs that are beta interferons like Avonex, such as Rebif from Serono SA, of Geneva, and Betaseron, sold by Montville, N.J.-based Berlex Laboratories. Witt called the BioMS drug "an altered peptide ligand, more like glatiramer than the beta interferons." Giese told BioWorld Today that the approach with MBP8298 is to create tolerance by intravenously giving high doses to "shut down the immune response and, in essence, re-educate it to not attack the body like it's doing."

Decision Resources estimated peak-year sales of the drug at $250 million, but that estimate does not take in Canada, which could be sizable. Giese noted the total relapsing/remitting market has been estimated at $4 billion.

"Pricing models are assumed to be similar" for the BioMS drug to those of the relapsing/remitting therapies, Giese said.

Tysabri "has a better dosing regimen, gets infused once a month and seems to have a better efficacy" and "is priced at a premium to the existing drugs," he added. Biogen Idec's partner, Elan Corp. plc, of Dublin, Ireland, said late last month that the wholesale acquisition cost of Tysabri will be about $1,808 per vial. With each patient requiring about 13 infusions a year, that price means the new MS drug will cost a patient about $23,500 annually.

Competing MS products range between about $13,000 and $16,000 per year. Giese said MBP8298 probably will land "somewhere in the range" between the top end of the competing drugs and the Tysabri price.