Lymerix Two-Month Dose Expected By Mid-2000, Pediatric Data By Year-End

SmithKline Beecham's Lymerix two-month accelerated dosing regimen could receive FDA approval in the first half of 2000, Jean-Pierre Garnier, PhD, said Sept. 16 at the Bear Stearns health care conference in New York City.

"We need to do some work on Lymerix, which is doing okay but is certainly not doing fantastic," Garnier acknowledged. "In terms of use of the product, there are some hurdles. And consumers are quick at pointing" those out.

"The way in which the vaccine must be administered is cumbersome," Garnier said. The Lymerix application was approved Dec. 21, 1998 with a three-shot schedule at zero, one, and 12 months (¹ (Also see "LYMErix Two-Dose Efficacy Data Provides 1999 Tick Season Benchmark" - Pink Sheet, 4 Jan, 1999.)).

Under the new schedule, vaccine is given at zero, one, and two months "and then you are covered for the rest of the Lyme season," Garnier explained. "That is much more practical. We have had some difficulties explaining that to the FDA in the past but now they have accepted our file." SmithKline submitted the sBLA for the new regimen in May.

At its May 26 review of the Lyme disease vaccine, FDA's Vaccines & Related Biological Products Advisory Committee expressed concern that the 12 month dosing schedule could leave vaccinated patients unprotected during tick season between the second and third shot (² (Also see "SmithKline LYMErix Dosing Studies For Earlier Efficacy Urged By FDA Cmte." - Pink Sheet, 1 Jun, 1998.)).

Garnier emphasized the importance of obtaining pediatric approval for Lymerix, noting "that is where the market opportunity is." SB intends to file pediatric data by the end of 1999. Lymerix is approved for those 15 to 70 years old. SB reported that the vaccine contributed $37 mil. in revenues for the second half since its January launch (³ ).

SB's antibiotic Augmentin (amoxicillin/clavulanate) may be older but is also still a major contributor, Garnier told analysts. "The reason for its success, very simple: Contrary to most aging antibiotics, this one has not lost anything of its potency [or] its efficacy, and it is of course, a very safe drug."

In a comparison with Pfizer's Zithromax (azithromycin) in acute otitis media, Augmentin "beat the pants off" of the newer antibiotic, Garnier said. The multicenter study of 238 children six months to four years old with clinically confirmed acute otitis media demonstrated a bacterial eradication rate of 87% for Augmentin compared to 39% for Zithromax.

The company is also counting on new data on the dopamine agonist Requip (ropinirole) to stimulate sales of the Parkinson's therapy.

"We expect to accelerate the growth of Requip for a simple reason," Garnier said. "There was a milestone study in Parkinson's comparing levodopa, the standard treatment, to Requip. The problem with levodopa [is] it's very efficacious, but it creates tremendous dyskinesias over time....So the strategy would be to save levodopa for the end when nothing else works."

A five-year study of 268 patients with early Parkinson's disease showed a 5% incidence of dyskinesias in the Requip arm compared to 36% for levodopa monotherapy. When patients whose symptoms did not improve were given supplemental levodopa, 20% of Requip-plus-levadopa patients vs. 46% of levodopa-only patients developed dyskinesias.

The study "demonstrated that if you use Requip first and do not touch the levodopa, you control the patient and you decrease dramatically the incidence of dyskinesias," Garnier said.

Requip could also benefit from warnings added to competitor Pharmacia & Upjohn's Mirapex (pramipexole) regarding sudden sleep onset. Requip has not been directly associated with the side effect (⁴ (Also see "P&U "Dear Doctor" Letter Notes New Label Warning For Sleep Onset" - Pink Sheet, 27 Sep, 1999.)). The company also is developing a once-daily Requip with SkyePharma.

Garnier noted that SB is in the process of "helping Coulter with their submission" of Bexxar (iodine I 131 tositumomab ) following FDA's Aug. 27 "refuse-to-file" letter for the non-Hodgkin's lymphoma therapy. The companies intend to co-market the drug; a BLA was filed June 30 and granted priority review status.

Coulter "encountered some difficulties with FDA because of the way they presented the data," Garnier said. "It's not a question of missing trials or anything like that. It's just the presentation was not what the FDA expected. So we're helping them to put [it] in shape for filing in the near future." Coulter indicated that it would submit a new filing by mid-October (⁵ (Also see "SmithKline/Coulter Bexxar" - Pink Sheet, 6 Sep, 1999.)).