(To be discussed in part 3 of this article).

Picoplatin’s Potential Competitors

Due to its small size, the market for SCLC is not very active, in contrast to the lucrative market of non-small cell lung cnacer (NSCLC) that garner a great deal of attention from every major pharmaceutical company. Niche markets are often targeted by smaller companies who seek to get their foot in the door, generating initial proof-of-concept for the product as well as a modest stream of revenues. Exelixis’ (EXEL) XL184, which recently entered pivotal trial in medullary thyroid cancer (MTC), and Infinity’s (INFI) IPI-504 which is expected to enter a pivotal trial for gastrointestinal stromal tumors (GIST) this year are good examples for this trend. Both drugs may be applicable in larger indications, but the companies decided to initially target niche markets.

The competitive landscape in the resistant/refractory SCLC market made it a suitable route to commercialization for small biotechs such as Poniard. Because there is no currently approved drug for this indication, picoplatin’s chances of showing a survival benefit and getting approved seem fairly high, while the overall market is still substantial. There are estimated to be 70,000 SCLC patients in developed courtiers who relapse following initial chemotherapy with a platinum agent. Around 40,000 of these patients fall under the definition “refractory/relapsed” as defined in the SPEAR trial. Assuming an average drug cost of $10,000 per patient (the cost of topotecan for the recommended 4 cycle treatment), picoplatin’s addressable market in developed countries is around $400 million. If picoplatin becomes the standard of care in resistant/refractory patients, it will likely be used off-label in sensitive patients as well.

Unfortunately, with the recent emergence of two potential competitors, Poniard might find out that turning picoplatin into the standard treatment for refractory/relapsed SCLC is more challenging than expected.

The first potential competitor is oral topotecan. The drug was developed with the goal of replacing IV topotecan for the treatment of second line sensitive SCLC patients, in order to provide them with a more convenient option. The trial compared oral topotecan combined with BSC vs. BSC alone, and showed a benefit in median survival (26 weeks vs. 14 weeks), similarly to the IV version of the drug. This trial led to the approval of oral topotecan only for sensitive SCLC patients, so allegedly it should not pose any threat to picoplatin. However, almost a third of the patients in the trial were refractory/resistant, and apparently these patients, who were traditionally considered non-responsive to topotecan, have actually responded quite well to the drug with a median survival of 23.3 weeks. This set of data might encourage GSK to try and get oral topotecan approved for resistant/refractory SCLC patients as well, even though the company has not disclosed any plans of doing so (yet). Furthermore, the results may encourage physicians to use topotecan for resistant/refractory patients even before approval. The lead investigators of the study left little room for speculation as they wrote:

“This study suggests that with oral topotecan the benefits of therapy outweigh the risks in all patient groups and therefore all subgroups of patients with relapsed SCLC (sensitive or resistant) should now be considered for this treatment.”

Phase III trials tend to result in shorter survival, compared to uncontrolled phase II trials, so if history is of any indication, picoplatin will probably have a lower benefit in the phase III trial compared to the 27 weeks in the phase II trial. Results may be slightly better than expected because the SPEAR trial includes some patients who had a better response to first line platinum therapy, but in general, it is possible that picoplatin will have only a slight or no advantage over oral topotecan. Assuming that picoplatin and oral topotecan have comparable survival benefits, picoplatin will have to prove advantageous based on other factors, such as, patient convenience, safety profile and financial feasibility.

Oral topotecan has definitely the upper hand in terms of ease of administration, as it can be taken as a pill. In addition, Poniard does not have the worldwide marketing and distribution resources GSK does, which should make worldwide market penetration challenging without a large partner. Picoplatin, on the other hand, seem to have a much better safety profile, as topotecan leads to a substantially higher incidence of severe side effects and a 6% mortality rate.

On top of the obvious quality of life issue, an unfavorable safety profile translates into additional medical costs that can sometimes overshadow the direct costs of the drug, and on that front, Poniard should have plenty of ammunition to throw at topotecan.

Over the past years, several studies evaluated the associated cost of topotecan’s toxicity in second line ovarian cancer patients, a setting that mirrors to some extent second line SCLC. In several different studies, the cost of topotecan was compared to that of another chemo agent ,lyposomal doxorubicin, (Doxil) which has a similar efficacy. The graph below summarizes some of the data from the cost analysis studies.

Although there is some degree of inconsistency among the studies and the associated costs, they all demonstrate the economic implications of severe side effects. Topotecan was cheaper in all studies, but its toxicity-associated costs were substantially higher and made it less economically feasible.