Although there remains no cure for psoriasis, presenters at the 60th annual meeting of the American Academy of Dermatology in New Orleans managed, at the very least, to provide hope for those burdened with the affliction.
From Seattle-based Immunex Corp.’s positive Phase II data from its Enbrel trial and good results seen with Malvern, Pa.-based Centocor Inc.’s Remicade, to products in development from Genentech Inc. (with partner XOMA Ltd.) and Biogen Inc., biotechnology companies are breathing hard down the neck of psoriasis. (See BioWorld Today, Feb. 25, 2002.)
Isis Pharmaceuticals Inc., however, presented mixed Phase II data on its intercellular adhesion molecule-1 inhibitor, ISIS 2302. It missed one endpoint in the study, but the company came away encouraged by the activity seen from the topical formulation.
South San Francisco-based Genentech and XOMA, of Berkeley, Calif., presented additional results from two Phase III studies of Xanelim (efalizumab), suggesting that some patients may experience longer periods of benefit when treated for 24 weeks.
“We’re very encouraged with the data we’ve seen,” said Lisa Skibsted, of XOMA’s corporate communications and investor relations department. “We have 24-week data that very clearly confirms what we saw in earlier studies. We are hopeful that the [data] show a continuous increase in benefit as patients continue on beyond the 24-week period on Xanelim.”
A total of 597 patients were randomized to receive weekly subcutaneous doses of 1 mg/kg or 2 mg/kg of Xanelim or placebo for the first 12-week treatment period. At 12 weeks, 258 patients who were either responders or partial responders again were randomized to receive 2 mg/kg of Xanelim weekly, 2 mg/kg of Xanelim every other week, or placebo for an additional 12 weeks. Responders were defined as achieving 75 percent or greater psoriasis area and severity index (PASI) score improvement; partial responders were defined as achieving 50 percent to 74 percent PASI score improvement.
After 24 weeks of Xanelim therapy, 76 percent of responders during the first 12 weeks of treatment maintained 75 percent or greater PASI score improvement when randomized to receive 2 mg/kg of Xanelim weekly or every other week for an additional 12 weeks. More than 30 percent of responders had 90 percent or greater PASI improvement from baseline. In addition, 24-week treatment increased the response rate for patients who were partial responders after 12 weeks. Of the 138 partial responders, 53 percent became responders with continued weekly Xanelim therapy of 2 mg/kg and another 29 percent became responders with continued Xanelim therapy of 2 mg/kg every other week.
Another presentation based on data from a combined analysis of two Phase III trials suggested Xanelim provides early clinical improvement in patients with moderate to severe psoriasis.
The regulatory filing of Xanelim was pushed back last year after the FDA asked for a study to confirm the equivalence of materials used for testing and manufacturing the drug. The 12-week study is under way, Skibsted said. (See BioWorld Today, Oct. 8, 2001.)
“It’s ongoing it completed enrollment at the end of December,” she told BioWorld Today. “Right now we are anticipating filing [a BLA] in the summer.”
Separately, XOMA said it entered a cross-licensing agreement with MorphoSys AG, of Munich, Germany, for antibody-related technologies. XOMA will receive a license to use MorphoSys’ HuCAL Gold antibody library for target discovery and research for five years, as well as license payments, and MorphoSys and its partners receive a license to use XOMA antibody expression technology for developing antibody products using MorphoSys’ phage display-based HuCAL antibody library. Deals like these help XOMA keep digging for drugs, Skibsted said.
Biogen, of Cambridge, Mass., conducted more than 15 oral and poster presentations featuring its psoriasis drug, Amevive, at the meeting, which included data from a Phase III intramuscular trial and safety and immunogenicity data gathered from other Amevive Phase III studies.
Eric Schmidt, an analyst with SG Cowen Securities Corp. in New York, said the data were “uniformly good and consistent with our prior expectations.” The data, Schmidt said, increased “our confidence that Amevive is safe, efficacious and approvable.” Schmidt believes Amevive “should receive a positive recommendation for approval” at a mid-year or second-half FDA panel meeting.
Isis, of Carlsbad, Calif., presented mixed Phase II data from its second trial of ISIS 2302 (alicaforsen), an intercellular adhesion molecule (ICAM-1) inhibitor, in patients with mild to moderate plaque psoriasis. ISIS 2302, a topical formulation, demonstrated a statistically significant improvement in investigator’s global response score at week four (p=0.02) but missed statistical significance at week eight (p=0.206). Alicaforsen achieved a 31 percent improvement from baseline measurement in plaque induration, at weeks four and eight (p=0.013 and p=0.034, respectively), and confirmed trends from a prior study, Isis said.
“I think the best way to describe the results is this: We were able to see two things that were very positive in our estimation we had statistically significant proof of principle and we saw drug in our biopsies,” Mark Wedel, executive director of clinical development at Isis, told BioWorld Today. “The reason we are excited about this is that we believe that this is the base we need to go forward with antisense in dermatology.”
Isis’ stock (NASDAQ:ISIS) fell $2.55 Monday, or 14.2 percent, to close at $15.40.
The company is developing a second topically formulated product for psoriasis ISIS 104838, a second-generation antisense inhibitor of TNF-alpha, and Wedel said that the activity seen in the ISIS 2302 trial “fans the flames of excitement for topical therapy for antisense.”
“We have several targets we can inhibit,” he said. “They can be inhibited systemically for sure, but now we have the option for topical.”
In a research note by Dennis Harp, analyst with Deutsche Banc Alex. Brown Inc. in New York, he cast his vote for Xanelim as having a slight competitive advantage over the late-stage psoriasis products the others being Enbrel, Remicade and MEDI-507, developed by MedImmune Inc., of Gaithersburg, Md. due to its “optimal balance of convenience, safety and efficacy.” But, Harp said, his firm believes “that there will be a market opportunity for all therapies.”