Cancer Clinical Trials and Treatments Late Stage Developments

Six bottles of chemotherapeutic agents for inj...Image via WikipediaFrom FierceBiotech

For the cancer drug research enthusiast, this report might read in places like a special oncology edition of a gun magazine. Indeed, there are plenty of weapons against cancer to read about here. Several of the drugs listed here represent the advancement of relatively new methods of attacking cancer, including "armed antibodies" and cancer-killing viruses.

 In addition, decades of basic research into the molecular drivers of cancer growth are bearing fruit for drug developers. Not only are these companies making progress in clinical trials, they have landed buyout deals and lucrative partnerships. It's also clear that relatively small companies like Aveo Pharmaceuticals and Curis are making inroads along side the big boys like Pfizer and Roche.

There are 10 late-stage drugs listed in this report, but this editor hesitates to call them the "Top 10" only because there are so many variables to consider to rank them in such a way objectively. Yet these 10 drugs have certainly been generating news and, in most cases, lots of interest among investors and the medical community. All of the drugs have reached pivotal trials for at least one type of cancer.
Here's the list in alphabetical order by each drug's most commonly used moniker, whether that is its alphanumeric code name or generic name. As always, please let us know whether you think there are cancer drugs in pivotal trials that you think should have been on this list or ones on this list that shouldn't be.

1. Carfilzomib - multiple myeloma
2. Crizotinib (PF-02341066) - lung cancer
3. GDC-0449 (vismodegib) - basal cell carcinoma
4. OncoVex - advanced melanoma
5. PLX4032 (RG7204) - melanoma
6. Ponatinib - leukemia
7. SGN-35 (brentuximab vedotin) - Hodgkin's lymphoma, anaplastic large cell lymphomas
8. Tivozanib (AV-951) - advanced renal cell carcinoma
9. T-DM1 (Trastuzumab-DM1) - breast cancer
10. XL184 (cabozantinib) -  prostate cancer

Onyx (ONXX)
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While Onyx Pharmaceuticals ($ONXX) has an approved kidney and liver cancer drug in Nexavar (sorafenib), much of the company's future value growth seems to be tied to its late-stage proteasome inhibitor carfilzomib.

In multiple myeloma, carfilzomib could offer some advantages over existing treatments for the plasma cancer such as reduced nerve damage, according to Onyx. The drug works by selectively inhibiting a protein complex in cells called the proteasome in order to make cancer cells more vulnerable to cell death. In December the firm revealed some promising Phase II data, showing that 24 percent of patients who took the drug after their cancers failed to respond to other therapies had at least a partial response.  

Onyx is now conducting Phase III trials that aim to support its bids for approval of the drug for multiple myeloma in the U.S. and Europe. The company said it expanded its European trial in March, bringing the number of patients in the study from 84 to 300 and making overall survival the primary goal of the study rather than progression-free survival-a move that analysts at J.P. Morgan Research viewed as a positive because demonstrating survival benefits could differentiate the drug label among those of other myeloma treatments.
Onyx expects to complete submission of its application for FDA approval of the drug by mid-2011.

Pfizer (PFE)
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The knock on Pfizer's ($PFE) crizotinib is that it only targets a tiny percentage of lung cancer patients, but the important thing is that the drug appears to have an impact for that tiny percentage.

Pfizer seems to be on schedule to complete a submission in the first half of this year for FDA approval of the drug for patients whose non-small cell lung cancer expressed the anaplastic lymphoma kinase (ALK) gene, which is found in 3-5 percent of patients with the disease. While potential sales of this drug aren't expected to reach blockbuster levels, Pfizer has signaled through its emphasis on targeted drug development and investments in rare diseases treatments that it's happy to be in niche markets with important new drugs.

Last year Pfizer provided details from an early-state clinical data showing that 46 of 82 patients with NSCLC who took the drug had a partial response to the drug and one patient had a complete response. The company also reported last year that patients on averaged lived for 9.2 months without their cancer getting worse.  A key in these studies was making sure that patients who took the drug had cancer with ALK mutations. When present, the mutations drive tumor growth and survival. 

Curis (CRIS)
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GDC-0449 might be one of many cancer drugs in the pipeline at Genentech, but for its partner Lexington, MA-based Curis ($CRIS) this drug is the most advanced compound in its pipeline. Swiss drug giant Roche, the owner of Genentech, has told Curis that it could make at least one regulatory submission for approval for the compound as a treatment for a common form of skin cancer called basal cell carcinoma (BCC) in 2011.
In March, Curis announced that Genentech's Phase II study of the drug in inoperable BCC patients met its primary goal of shrinking tumors of a certain percentage of patients. This was good news after the drug flunked in mid-stage studies Genentech conducted in patients with ovarian and colorectal cancers last year. Curis, which does not yet have a drug on the market, is eligible for up to $115 million in milestone payments through this program with Roche/Genentech as well as single-digit royalties on potential sales.

Amgen (AMGN)

Amgen ($AMGN) made a huge bet on OncoVex in January with the buyout of the drug's Woburn, MA-based developer, BioVex, in a deal worth up to $1 billion. Later this year Amgen expects to see primary outcome data from a Phase III trial of the drug in patients with advanced melanoma, according to ClinicalTrials.gov. The company can only hope that the trial yields results as impressive as those from a small mid-stage trial in patients with the deadly skin cancer.

OncoVex attacks tumors in two ways. It features a modified cold sore virus that replicates inside solid tumors, causing cancer cells to die. Secondly, the drug prompts the immune system to take out cancer cells. In May 2009, BioVex impressed with Phase II data on the drug in melanoma patients, showing that of 13 patients who had significant responses to the treatment, nine had signs of the cancer completely wiped out.
Amgen is eying multiple markets for OncoVex, a late-stage trial for which is now recruiting patients with head and neck cancers. The drug has also shown potential to treat patients with breast and pancreatic cancers.

Daiichi Sankyo  (DSKYF)
Daiichi SankyoImage via Wikipedia

Plexxikon is sitting pretty right now, largely due to the stellar performance of its lead experimental drug, code named PLX4032. After the Berkeley, CA-based firm and its partner Roche reported exciting data from trials of the drug in patients with melanoma over the past year, Japan's Daiichi Sankyo swooped in and bought Plexxikon in a $935 million deal revealed in February. What's more, Plexxikon CEO Peter Hirth told FierceBiotech that the company's Japanese owner plans to give the small drug developer a degree of autonomy and funding to continue its impressive work.

Plexxikon reported in January that melanoma patients on the drug in a Phase III trial were showing better overall survival and on average were living longer without their cancer progressing than those who were on the standard therapy for melanoma, dacarbazine. The drug is targeted for patients with a BFAF mutation. Roche is developing a DNA-based test to identify patients with the BRAF mutation, which causes unchecked cell growth and cancer. In general, BRAF mutations show up in most melanomas.

Plexxikon, a 2010 Fierce 15 company, published Phase I data in an August 2010 issue of the New England Journal of Medicine. The article said that 81 percent of melanoma patients on the drug had their tumors shrink by at least 30 percent.

Ariad Pharmaceuticals (ARIA)
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The big story at Cambridge, MA-based Ariad Pharmaceuticals ($ARIA) is its leukemia drug ponatinib, despite the fact that its lead experimental cancer drug is ridaforolimus (which is advancing in partnership with Merck). Ponatinib is now in a pivotal Phase II clinical trial as a treatment for patients with chronic myeloid leukemia or Philadelphia positive acute lymphoblastic leukemia whose cancers are resistant to Bristol-Myers Squibb's Sprycel or Novartis's Tasigna.

Ponatinib is designed to target multiple mutant forms of BCR-ABL fusion proteins, making it a potentially potent next-generation inhibitor of tyrosine kinases. In December the company reported that in a Phase I trial 66 percent of patients on the drug showed a major cytogenetic response, evidence that the drug was weakening their cancer (and such responses were shown in 100 percent of patients with a T315I mutation). The firm is interested in partnering on the development of ponatinib in certain markets outside of the U.S; so another pharma deal might be in the offing for the company.

Seattle Genetics (SGEN)  Takeda Pharmaceuticals (TKPHF)

After promising results in clinical trials revealed late last year, SGN-35 (brentuximab vedotin) has a shot at being approved later this year for immune system cancers known as Hodgkin's lymphoma and anaplastic large cell lymphomas that have been resistant to prior therapies or come back after a period of time.
Seattle Genetics ($SGEN) and Millennium: The Takeda Oncology Company reported in December that the drug--which is an anti-CD30 monoclonal antibody linked to cancer-killing agent called an auristatin--completely wiped out visible signs of disease in just more than half of the 58 patients with forms of anaplastic large cell lymphomas in a Phase II study, with an additional third of the patients' tumors shrinking by at least half.

In a pivotal trial involving 102 patients with relapsed or resistant Hodgkin's lymphoma, the drug rendered the cancer undetectable in 34 percent of patients and provided partial remissions for 40 percent of volunteers in the trial. Seattle Genetics has U.S. and Canadian marketing rights to the drug, and Takeda controls commercialization of the treatment in the rest of the world.

Aveo Pharmaceuticals (AVEO)
Image representing AVEO Pharmaceuticals as dep...Image via CrunchBase

Tuan Ha-Ngoc, the president and CEO of Aveo Pharmaceuticals ($AVEO), is leading a very smart charge to advance tivozanib to the market for kidney cancers called advanced renal cell carcinoma (RCC).
In June 2010, the company showed results from a Phase II study of a the drug--a potent blocker of all three vascular endothelial growth factor (VEGF) receptors, which play a role in the formation of blood vessels that feed tumors--that patients taking the drug on average lived without their cancer getting worse for 11.8 months. That same key indicator of effectiveness was nearly 14.8 months among patients with a clear cell form of RCC who had prior surgeries to remove at least part of their kidneys.

In the company's 517-patient Phase III trial comparing tivozanib head-to-head with Onyx Pharmaceuticals' and Bayer's Nexavar, patients who enter the study must have a clear cell form of the disease and previously have had the surgery to be eligible (the types of patients who did really well in the Phase II study). Aveo plans to report results of the trial in mid-2011. It's also worth keeping an eye on Pfizer's similar drug, axitinib, for which the drug giant plans to submit in 2011 applications for U.S. and European regulatory approvals as a treatment for patients with kidney cancer.

Aveo is sharing equally North American and European development costs and profits related to tivozanib with Japan's Astellas Pharma. Kyowa Hakko Kirin has rights to develop and commercialize the drug in Asia.

ImmunoGen (IMGN)

Here's more evidence that linking targeting antibodies with cancer-killing drugs can pack a powerful one-two punch against tumors. This "armed antibody" drug due to be submitted (again) for regulatory approval in mid-2012. T-DM1 has been shining in clinical trials involving women with breast cancer for years, but the FDA handed back Swiss drug giant Roche's application for approval of the drug in August 2010. That application was made with promising Phase II data on the treatment, but regulators apparently want to see results from larger studies underway.

\T-DM1 is truly a two-pronged weapon against breast tumors. It uses linker technology from Waltham, MA-based ImmunoGen ($IMGN) to equip Roche's Herceptin, an antibody that binds to HER2-expressing breast tumors, with a cell-killing agent known as DM1. This enables the antibody to home in on the cancer target and deliver the cell-killing agent into tumor cells.

Preliminary data released in October from a 137-patient Phase II study showed that 47.8 percent of breast cancer patients on T-DM1 had a confirmed objective response on T-DM1, compared with 41.4 percent who were taking a combination of Herceptin and a chemotherapy drug, taxane.

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