Bristol-Myers, ImClone, Genentech Release Promising Data at ASCO

One of the pharmaceutical industry’s biggest and most high profile society conferences is the American Society of Clinical Oncology, or ASCO, meeting. This year’s ASCO meeting was held here in Chicago, and Jason Napodano, CFA, our Senior Pharma/Biotech analyst, is here to give us the inside scoop.

Jason, welcome back.

Always a pleasure!

So the big news heading into the conference was this expected data from Bristol (BMY) and ImClone (IMCL) on Erbitux for lung cancer. How did the data pan out, and did it live up to the lofty expectations?

This was the story last week, Mark. Bristol and ImClone announced they were going to present data from the FLEX – or First-line in Lung cancer with Erbitux – phase III study. The trial was designed to test Erbitux in patients with advanced (stage IIIb/IV) non-small cell lung cancer [NSCLC] when combined with standard platinum-based chemotherapy (cisplatin/vinorelbine).

The results showed that adding Erbitux to chemotherapy extended the overall survival rate to 11.3 months from the 10.1 months with chemotherapy alone. This was statistically significant at p=0.044, just beating the standard p<0.05 FDA threshold. So to answer the first part of your question Mark, yes, this was clearly encouraging data.

However, did it live up to expectations? I’d say not really. And the reason here is that Genentech’s (DNA) Avastin, when tested in a similar advanced (stage IIIb/IV) non-small cell lung cancer population in 2006 improved overall survival rates to 12.3 months vs. 10.3 months for chemotherapy alone. Now the chemotherapy in that Genentech (Study E4599) trial was slightly different, using paclitaxel/carboplatin, but with the chemotherapy control groups offering such similar survival rates, I think most oncologists will agree that Avastin is the superior first-line choice to Erbitux. That’s not to say Erbitux won’t benefit from these data, but it looks like Avastin is still the top dog in NSCLC.

Now ImClone had some additional data with Erbitux on colon cancer patients too, correct?

Yeah, this was an interesting trial because what ImClone did was pre-screen patients for a genetic biomarker, in this case called “wild type” K-Ras that is found in about 65% of the metastatic colorectal cancer (mCRC) patients. And what the trial demonstrated is that patients expressing this non-mutated gene respond enormously better to a first-line Erbitux plus chemotherapy regimen than those with the mutated gene.

So it’s an interesting strategy here. Oncologists will be encouraged to screen their patients for this “wild type” gene before treatment. If they have the gene, then Erbitux seems like an excellent choice. If they do not have the gene, then there seems to be little reason to prescribe Erbitux.

Now in this first-line mCRC population, oncologists can pick from Avastin or Erbitux, and it may be the presence of this K-Ras gene that is the deciding factor. I think it’s important to note that Genentech is doing the same sort of biomarker analysis with Avastin: pre-screening patients to see which type of commonly found mutations have an impact on Avastin results.

Let’s stick with Genentech and its blockbuster drug Avastin. Some good news for breast cancer patients was released this weekend, it seems?

Genentech released results from the AVADO trial testing Avastin in first-line advanced HER2-Negative metastatic breast cancer. Remember, this was an indication the FDA recently granted Accelerated Approval for in February 2008, and as part of the approval stipulation, data from the AVADO trial must be submitted in a supplemental application. So, good news for Genentech and breast cancer patients that this trial hit the primary endpoint in extending what’s known as progression-free survival [PFS] vs. chemotherapy alone, 8.8 months vs. 8.0 months, respectively.

We seem to be talking about Avastin an awful lot, Jason. How big can this drug get for Genentech?

It’s truly a mega-blockbuster, Mark, and a clear breakthrough for solid tumor cancers. We haven’t even hit on the positive phase II data released this weekend in glioblastoma multiforme [GBM], or brain cancer, a cancer in the recent spotlight due to the illness of Senator Ted Kennedy. Another notch in the Avastin belt, so to speak, with this data.

But to answer your question, we think Avastin can post sales of $2.8 billion in 2008. That’s U.S. sales only. By 2012, we would not be surprised to see Avastin posting U.S. sales close to $5.0 billion. Roche controls sales outside the U.S., and the market is about the same size. So when you look on a global basis, this is one of the largest pharmaceutical products in the world. The drug is a biologic – monoclonal antibody – and just shows the potential power of what the biotech industry can achieve.

Excellent update, Jason. Anything else we should keep an eye on?

The only other thing I’ll mention is that Bristol-Myers, a stock we have a Buy rating on, offered up some encouraging data on its metastatic melanoma, or skin cancer, drug, ipilimumab. This is a drug that most of the Street has written off given some past mixed results and the failure of a similar drug at Pfizer (PFE). However, Bristol may have resurrected its ipilimumab chances with some preliminary data presented this weekend.

The data are early and we are still analyzing the results, so I won’t go into the details, but that would definitely fit under your category of something to keep an eye on. I’d say Bristol, with Erbitux and ipilimumab, was a big winner this weekend at ASCO. Genentech always seems to have a great ASCO conference. Celgene (CELG), covered by my colleague Grant Zeng, also had a very good conference, but I’ll leave it to Grant to fill you in.

Jason Napodano, CFA is a senior analyst covering the pharmaceutical and biotechnology sector for Zacks Equity Research.

Comments

[pharma]

Half-truth is bad. It is more bad than lies. But this is exactly what Jason Napodano provides his readers.

Yes indeed, in general ITT [intend to treat] patient population adding Erbitux to chemotherapy extended the overall survival rate to 11.3 months from the 10.1 months for chemotherapy alone.

But this is not the entire story. Flex trial patients population included substantially broader spectrum of patients than the Avastin trial Jason Napodano has mentioned.

So let compare apples with apples:

- the Avastin trial #E4599 was conducted exclusively in Adeno-ca lung cancer patients. Addition of Avastin to chemotherapy improved median survival rates from 10.3 months to 12.3 months. Furthermore, cancer patients in Avastin #E4599 trials were ECOG 0-1 [relatively "healthy" patients] compare with more sick FLEX patients with ECOG 0-2.

In these more sick Adeno-ca lung cancer patients, addition of Erbitux to chemotherapy improved median survival from 10.2 months to 12 months. FLEX Erbitux median survival benefits to more difficult to treat lung cancer patients were practically identical to Avastin.

- But it is not all. FLEX ITT patient population also included SCC- lung cancer patients. These cancer patients can NOT be treated by Avastin due to severe life-threatening side-effects. In this lung cancer population, addition of Erbitux to chemotherapy improved median survival from 8.9 months to 10.2 months.

- It is true, Erbitux did not work on Asian patients. Addition of Erbitux to chemotherapy reduced these patients median survival. Erbutux should not be used in Asian lung-cancer patients.

- Avastin and Erbitux belong to two different classes of drugs. Erbitux is a EGFr-drug. It offers substantial clinical benefits to only a select group of patients and no benefits to the rest. By identifying Erbitux-responding patients [like it is done using biomarkers in colorectal cancers], survival benefits offered by Erbitux are much superior to Avastin benefits.

- Finally, the latest Avastin clinical trials in lung cancer failed to show survival benefits. Consequently, effictiviness of Avastin in lung-cancer became an issue.

[Ax]

I agree completely with the post above from pharma... although I am no expert on medical studies. I think the reporting about the new drug Erbitux was just spin. The market and the media wanted to see Genentech drug to look superior.

The reports focused only on the 40% that the Erbitux drug doesn't apply too... and no one mentioned the other 60%. When you get a drug that shows superior results on a specific segment of people, there is no doubt that the drug will be prescribed to them.

Also we must not forget that when Mike Huckman asked at the ASCO the doctors if they would prescribe Erbitux to their patients the vast majority said yes. And the one that wasn't sure was from Canada.

[xzorro123]

It is a pity that not also is commented on the 3 encouraging clinical trials of Genvec for :
1. pancreatic tumor- Phase 3
2. esophageal tumor- Phase 2
3. Head and neck tumor: Phase 1

Genentech is a MegaCap company and GNVC is a SmallCap company. Hence, the effect on GNVC s.p. is most likely more significant.

DYODD

[pharma]

AX,

"Also we must not forget that when Mike Huckman asked at the ASCO the doctors if they would prescribe Erbitux to their patients the vast majority said yes. And the one that wasn't sure was from Canada."

It is important to mention that Erbitux is not available in Canada. Bristol (who does Erbitux marketing in North America) is still negotiating with Canadian government Erbitux's price sold there.

[Ax]

Pharma,

that makes more sense, yeah. The Canadian doc. mentioned the costs... I guess it was because of the negotiations you mentioned. OK.