huN901-DM1, which is the second wholly-owned candidate Immunogen is currently evaluating in clinical trials, comprises the huN901 antibody, which targets CD56 and the DM1 cell-killing agent. CD56 is mainly expressed by multiple myeloma, small-cell lung (SCLC) and ovarian cancers. Small-cell lung cancer accounts for ~20% of all lung cancers cases, with 214,000 cases estimated in 2007. While the response rates to chemotherapy are very high, ultimately, the majority of patients will relapse within a year from the treatment start.
huN901-DM1 is currently being evaluated in 3 different clinical trials, prosaically titled 001,002 & 003:
Study 001 is a phase II trial which was designed to evaluate huN901-DM1 for the treatment of SCLC. Recently, the company presented results from this trial in ASCO 2007. The trial started as a dose escalation trial, until Maximum Tolerated Dose (MTD) was set at 60mg/m2/week for four consecutive weeks every six weeks.
Out of the 30 evaluated patients, 13 patients were treated with doses lower than the MTD. 2 patients had a partial response and 5 had stable disease, which is not a spectacular response rate, but definitely justifies additional evaluations.
Study 002 is a phase I trial evaluating huN901-DM1 for the treatment of SCLC and other CD56-expressing solid tumors. The dosing in this trial is somewhat more aggressive in comparison to the 001 trial, as the compound is dosed daily for three days in a 21-day cycle with doses starting at 12 mg/m2 to 225 mg/m2 over three days. The last update from this trial was reported in November of 2006, after evaluating 41 patients. This trial was also a dose-escalation trial, which means that many of the patients were administered with lower doses. Out of the 41 patients, there was one complete response in a patient with relapsed Merkel cell cancer (a rare type of skin cancer) which lasted 21 months (At the time of data presentation), one partial response in a patient with SCLC and 13 patients with stable disease, two of which lasted for 18 weeks. MTD has not been reached, which means there is room for higher doses to be evaluated. This trial’s MTD will be much higher than the one achieved in the 001 study, which led the company to give the 002 study priority over study 001. Due to supply constraints, Immunogen is yet to enroll additional patients in the 002 trial, however, the company expects to start additional dosing very soon.
Study 003 is the reason for the delay in patient recruitment for study 002. This study evaluates huN901-DM1 for the treatment of relapsed multiple myeloma, a very common blood cancer that expresses CD56 in 70% of the cases. According to the American Cancer Society, approximately 20,000 new cases of multiple myeloma will be diagnosed in the USA in 2007, and close to 11,000 people will die from the disease. Fortunately for patients, the competitive landscape in the multiple myeloma market has become very tough, with 3 highly effective drugs gaining FDA approval in the past 5 years: bortezomib (Millennium’s Velcade®) thalidomide (Celgene’s Thalomid®) and lenalidomide (Celgene’s Revlimid®). All three have demonstrated substantial activity as single agents as well as in combination regimens for early and advanced stages multiple myeloma.
Since the company sees this trial as the most promising opportunity for huN901-DM1, and is currently limited in the amount of drug it can manufacture, it decided to give it priority over the 001 and 002 trials. So far, only preliminary results were reported from this trial, evaluating only 2 cohorts of 3 patients each, with huN901-DM1 administered weekly for two weeks in a three-week cycle. The lower dose did not demonstrate clinical effect, however the higher dose (60 mg/m2/day) resulted in impressive results. One of the three patients receiving the higher, 60 mg/m2 dose level had an objective response to treatment and the other two patients receiving this dose showed evidence of clinical benefit. More importantly, the patient who achieved a partial response had previously been treated with thalidomide and lenalidomide, among other treatments. The company recruited more patients to be administered with higher doses, up to 112 mg/m2, and will report results at The American Society of Hematology’s (ASH) annual meeting this December.
company’s management sounds very enthusiastic in regard to the results of that follow on trial. Abstracts for ASH 2007 had to be submitted by August 21, with late-breaking abstract deadline set at October 9, so by now the data has probably been prepared and analyzed by the company. During a presentation at the BIO InvestorForum 2007 that took place on October 10, the company’s CFO again expressed a great deal of optimism regarding the evaluation of huN901-DM1 for multiple myeloma, calling it “the fastest route for the market”. We specifically see the company’s expectations build-up for ASH 2007 as a strong indication for the quality of results involving the 3 additional doses.
Author is long IMGN