The Most Disappointing Clinical Failures in 2014

Since roughly 90% of all clinical trials end in a failure, it isn't too shocking that 2014 boasted its fair share of clinical trial disappointments. But while failure is common and expected in the industry, some defeats were more disappointing than others. Read on to learn which three clinical trial failures our Motley Fool contributors think were the biggest busts.

Source: Flickr userAaron

Todd Campbell: In my view, the most disappointing trial failure this year has got to be Exelixis' study of cabozantinibin prostate cancer patients. Investors had high hopes for cabozantinib given that competing prostate cancer treatments developed byJohnson & Johnson andMedivation had gone on to achieve billion dollar sales run rates following their approval.

However, Exelixis shareholders weren't so lucky. Despite performing well enough in earlier stage studies to support Exelixis launching a large (and expensive) phase 3 study involving nearly 1,000 men, cabozantinib failed to demonstrate statistical significance in both disease progression and overall survival versus the control arm. That revelation resulted in Exelixis issuing pink slips to 70% of employees and investors enduring a 77% decline in the company's share price this year.

Following its failure, hope now shifts to the potential approval of cobimetinib, a drug that the company developed with Rocheand that was submitted earlier this month for FDA approval as a treatment for melanoma patients with the BRAF V600 mutation. Further out, there may still be a chance for cabozantinib. Exelixis is investigating its potential in kidney cancer and non-small cell lung cancer. Regardless, Exelixis failure is an important reminder of the risks tied to investing in biotech stocks.

Brian Orelli:Pfizer's lung cancer drug, dacomitinib, had not one but three clinical trial failures this year, all announced on the same day last January.

Dacomitinib is a pan-HER kinase inhibitor, meaning it hits HER1 -- also called EGFR -- HER2, and HER4. EGFR is a target of multiple drugs, so targeting two additional related proteins should work better?

Apparently not.

In two trials of lung patients that had already failed other therapies, dacomitinib wasn't able to increase progression-free survival -- the time it takes for the tumor to start growing again while the patient remains alive -- compared toRocheandAstellas' Tarceva, an EGFR inhibitor.

A third trial run by Canada's NCIC Clinical Trials Group also failed. In that trial, patients who had failed both chemotherapy and an EGFR tyrosine kinase inhibitor that were given dacomitinib didn't live any longer than those given placebo.

Pfizer has one more phase 3 trial, dubbed ARCHER 1050, that's testing dacomitinib as a first-line treatment compared toAstraZeneca's Iressa. That trial is scheduled to wrap up next year, so dacomitinib could be on 2015's list of clinical trial failures, although at this point, maybe it wouldn't be considered "disappointing" anymore.

The only good news from this fiasco is that Pfizer isn't funding the remaining trial. In 2012, Pfizer set up a collaboration with SFJ Pharmaceuticals in which SFJ agreed to provide funding and clinical development supervision of the ARCHER 1050 trial in exchange for milestone and earn-out payments if the first-line indication was approved.

George Budwell: One of the most disappointing clinical failures to me wasGlaxoSmithKline's cancer vaccine candidate, MAGE-A3. Last March, we learned that MAGE-A3 failed to improve disease-free survival (DFS), compared to placebo, in non-small cell lung cancer patients, making it the latest in a long line of high profile clinical failures for vaccines aimed at treating cancer. In 2013, MAGE-A3 also flamed out as a potential treatment for skin cancer.

What makes this latest failure particularly noteworthy is that it added to the growing skepticism in the industry about the future of cancer vaccines in general. Despite an intensive research effort, cancer vaccines have repeatedly flopped in clinical testing, or at best, have only shown marginal benefits, when compared to other available treatments -- such as Dendreon's Provenge for prostate cancer, andAmgen's T-Vec indicated for metastatic melanoma.

Going forward, I expect big pharma to continue to move away from cancer vaccines to focus on other types of immune-based therapies like checkpoint inhibitors. Unless something drastically changes, cancer vaccines no longer appear to be strong clinical candidates as monotherapies, and might only serve a minor role as "immune enhancers," when used in conjunction with other types of treatments.

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Brian Orelli has no position in any stocks mentioned. George Budwell has no position in any stocks mentioned. Todd Campbell owns shares of Exelixis and Medivation. The Motley Fool recommends Exelixis and Johnson & Johnson. The Motley Fool owns shares of Johnson & Johnson. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.

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