Of note, all the studies above involve IV topotecan, but the oral version seems to have a similar safety profile. For the same reason, the cost of administration is not included in the analysis.
The pertinent conclusion is that if picoplatin shows a comparable or even slightly worse efficacy profile, health insurers will prefer it over topotecan, based on financial considerations. The superior safety profile should also help picoplatin gaining acceptance among physicians and patients, many of whom are old and frail and consequently cannot tolerate intensive therapies.
Amrubicin
Picoplatin’s second potential competitor is Celgene’s (CELG) amrubicin, which is already approved in Japan for the treatment of lung cancer. Celgene gained access to amrubicin as a result of the Pharmion acquisition, which held the exclusive rights for the drug in the US and Europe, after acquiring San Diego-based Cabrellis. Amrubicin is currently in a registrational phase III trial, where it is being evaluated against topotecan among second-line SCLC patients, sensitive and resistant/refractory. Interestingly, results from the trial are expected to arrive in 2010, one year after the expected results from the picoplatin study.
Amrubicin previously demonstrated unprecedented clinical activity in several single arm clinical trials in Japan, with an overall survival above 40 weeks in second line SCLC. There was, however, some skepticism with respect to the reliability of these impressive results, which stemmed from ambiguous results in other trials as well as from the fact that amrubicin had never been evaluated outside of Japan. At this year’s ASCO annual meeting, three studies in second line SCLC were published, including two comparative trials in which amrubicin was evaluated head-to head with topotecan.
One randomized trial (#8040), run by Celgene in the US, compared amrubicin and topotecan in sensitive SCLC patients. Amrubicin had a better response rate as well as a 4.5 week difference in progression- free survival (PFS). In another randomized trial (#8042), this time in Japanese patients, amrubicin demonstrated superior activity over topotecan, with a 6 week difference in PFS. From Poniard’s perspective, these results make amrubicin a real threat, (assuming that picoplatin and topotecan have comparable efficacy), even though these trials involved primarily sensitive patients as opposed to the refractory/resistant population Poniard is targeting with picoplatin. It is also worth noting that Poniard targets a portion of the sensitive market as well with its ongoing phase III trial. On the safety front, picoplatin still looks advantageous, as amrubicin led to a high level of severe side effects, including 4 treatment-related deaths in the two studies. Nonetheless, it seems that unlike topotecan, amrubicin has the potential to lead to substantially better survival than picoplatin.
The third study (#8041) evaluated amrubicin in resistant/refractory SCLC patients in a single arm trial. Of the 69 evaluable patients, 12 (17.4%) achieved an objective response and the median PFS was 13.8 weeks. Picoplatin had a response rate and a median PFS of 10% and 9.1 weeks, respectively, in a similar patient population, another reason to worry about picoplatin’s prospects.
In the meantime, amrubicin remains the biggest threat to Poniard’s picoplatin. While in the case of topotecan, competition will be based primarily on safety and feasibility issues, ambrubicin might show several weeks advantage in overall survival over picoplatin, and replace it already in 2011, only one year after picoplatin is expected to hit the market.
If amrubicin is found to be more effective than picoplatin, Poniard will have several options. The first option will be abandoning the SCLC market and focus on larger markets. A second option is trying to combine picoplatin with amrubicin or topotecan given picoplatin’s promising safety profile. Topotecan, for example, was evaluated in combination with cisplatin in first line SCLC. The combination demonstrated similar efficacy and acceptable toxicity compared to standard therapy (etoposide with cisplatin), so it is reasonable to assume that it can also be combined with picoplatin. Combining amrubicin with cisplatin in a 2005 Japanese study resulted in promising clinical results, but again, the real value of this type of combination will have to be investigated in large, controlled trials. A third option might be targeting first line SCLC, by replacing the currently used platinum compounds.
In summary, picoplatin has a high probability of approval for the treatment of second line SCLC. The real challenges will come from potential competitors such as topotecan and amrubicin, if approved for overlapping indications. Amrubicin seems to be a more serious threat due its high activity in recent trials, but additional insight will be gained only when overall survival data from the amrubicin trials emerges later this year. On the safety front, picoplatin is superior, therefore, even a slightly worse efficacy profile relatively to topotecan or amrubicin should make it the standard of care.
As noted before, SCLC represents the shortest route to market for picoplatin but it is a relatively small market when compared to other indications for which platinum compounds are approved. The SCLC clinical program will hopefully provide the needed proof of concept for the activity of picoplatin and its superiority over available platinum compounds. This, coupled with positive results in other indications will help Poniard advance picoplatin in major indications such as prostate and colorectal cancer. However, In order to realize the full potential of picoplatin, Poniard will have strike a partnership deal with a large pharmaceutical company.
Author is long PARD & EXEL