Eli Lilly’s Alimta to change the treatment dynamics in non-small cell lung cancer

Eli Lilly's Alimta is set for launch in the US market having gained FDA approval for the treatment of lung cancer, caused by exposure to asbestos, in patients who are not candidates for surgery. Although likely to become the gold standard treatment in this area, Alimta could have a far greater impact on the wider market if approved for the treatment of non-small cell lung cancer.

In its research, Datamonitor analyzes the current lung cancer market and assesses the potential impact of key late-stage drugs in development for lung cancer, including global sales forecast to 2011. Significantly, Datamonitor also offers an epidemiology of non-small cell (NSCLC) and small cell lung cancer (SCLC) in the seven major markets.

Breakthrough treatment

On February 5, 2004, Alimta was approved by the FDA for the treatment of malignant mesothelioma in combination with cisplatin, after it was shown in a phase III trial that the combination conferred a three-month survival advantage over standard cisplatin therapy; the first time a survival advantage has been observed for mesothelioma.

Eli Lilly’s Alimta (pemetrexed) is a multi-targeted antifolate primarily inhibiting three folate-dependent enzymes: thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT), necessary for DNA and RNA synthesis, thereby inhibiting tumor growth.

The major clinical advantage anticipated from Alimta is the potentially enhanced efficacy due to the possibility of less resistance compared with single-targeted agents. If resistance were to develop by an increase in the level of one target enzyme, such as an upregulation of production of TS, the folate pathways would still be inhibited by the action of Alimta on the alternative target such as GARFT.

Targeting wider approval

Given the lack of an efficacious drug for mesothelioma, Alimta is expected to become the gold-standard therapy in a relatively short period of time. However, the limited patient potential of the disease, estimated to be approximately 10,000 new cases globally, means Alimta’s commercial potential in the indication is limited. The drug should therefore become a greater commercial success in the NSCLC market and more importantly, the introduction of Alimta is likely to significantly alter the treatment dynamics of NSCLC.

On the basis of phase III trial results, Alimta is likely to replace Aventis’s Taxotere (docetaxel) as the leading second-line therapy for NSCLC. The trial has shown that Alimta is as efficacious as Taxotere but less toxic. For NSCLC patients who fail initial therapy, further treatment options are limited. With limited life expectancy, it is unacceptable for these patients to suffer from toxicity. For this reason, a significant proportion of patients are likely to be treated with Alimta instead of Taxotere after first-line failure.

The availability of Alimta in second line means Taxotere can shift towards its use in first line, restricted up to now due to the lack of alternatives in second line. As a result, the treatment paradigm in NSCLC is likely to change considerably and potentially signal the end of Taxol’s dominance for NSCLC.

Future strategy

Eli Lilly’s own Gemzar (gemcitabine) may also be affected by the power shift towards Taxotere. Indianapolis-based Lilly will therefore be banking on the potential approval of Alimta in combination with Gemzar to replace platinum-based regimen as the gold-standard first-line NSCLC therapy, thereby avoiding the cannibalization of Gemzar’s sales by Alimta.

Lilly has already initiated a number of clinical trials of Gemzar in combination with Alimta, for mesothelioma, NSCLC, breast, ovarian, bladder and pancreatic cancer. Much of this clinical testing is however, in its early stages, making it unlikely that Lilly will gain approval for all of these indications before Gemzar’s patent expiry in 2010.

Datamonitor nevertheless anticipates that the potential off-label use of Alimta in addition to the drug's use in combination with Gemzar for these indications could produce considerable sales.

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