The OBR Blog

June 30, 2010 - 10:06 am Posted in Featured comments4 Comments

In keeping pace with today’s fast information outlets, MDOUTLOOK, powered by the ARCAS Group conducted a series of exclusive quick polls immediately after this year’s ASCO annual meeting exploring market adoption trends based on data presented at the meeting. Complete responses were received by 70 medical and hematologic oncologists for the immunotherapy quick poll and 120 for the hematology-oncology quick polls. Below is a summary of their findings.

Melanoma

Based on the presentations at ASCO, physicians found that the Phase 3 trial data on ipilimumab to be of high clinical importance.

The trial data presented on ipilimumab at ASCO showed improved overall survival (OS) in patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease with treatment with the anti-CTLA4 monoclonal antibody. According to the MDOUTLOOK survey, melanoma treaters will rapidly integrate ipilimumab in their armament (assuming it is approved) and virtually all of them will use the drug in at least some of their stage III melanoma patients. Additionally, all of the respondents said they will use ipilimumab at least in some of their stage IV patients. Roughly one-third will try ipilimumab in the majority of their late-stage patients.

 

Renal Cell Carcinoma

The respondents also responded positively to the data presented on metastatic renal cell carcinoma (mRCC). Results from the SELECT trial—identifying patients with mRCC likely to respond to treatment with high-dose IL-2—showed improved patient selection doubles the response rate to HD IL-2 in mRCC. Although the excitement on the data from the SELECT trial is viewed optimistically by oncologists, it was not met with the same level of “excitement” as ipilimumab.

Prostate Cancer

Approved by the FDA on April 30, 2010 for the treatment of prostate cancer resistant to standard hormone therapy, the active cellular immunotherapy Provenge [sipuleucel-T; Dendreon] had a moderate market adoption response by physicians. There were 2 main groups of initial users: 1) those using in a small (<10%) group of patients; and 2) those using in about one-fourth of their patients. Few, if any, physicians see sipuleucel-T as a main therapy option, at least initially. This could simply be due to manufacturing issues. According to Dendreon COO Hans Bishop, in a June 28 Bloomberg Businessweek article, he stated that currently the company can only make enough Provenge to treat about 2% of eligible patients until manufacturing increases in mid-2011.

Follicular Lymphoma

In another post-ASCO quick poll of hematologists and medical oncologists with an interest in hematologic malignancies (N=120), MDOUTLOOK found that when it comes to follicular lymphoma (FL), roughly 70% of physicians use rituximab [Rituxan; Genentech] in the vast majority of their FL patients—(81%-100% of patients receiving treatment).

Based on new information presented at ASCO 2010, the use of rituximab as maintenance therapy in FL is predicted to increase.

Multiple Myeloma

Also expected to increase in use is lenalidomide [Revlimid; Celgene] as maintenance therapy in patients with multiple myeloma (MM) as a result of data presented at ASCO. About three-fourths of physicians are already using lenalidomide as maintenance therapy for MM, and following the ASCO presentations on lenalidomide the use of the therapy is expected to increase to >90% of physicians. More importantly, over half of MM patients are predicted to receive lenalidomide maintenance—up from the one-third that currently receive the drug—primarily due to a large increase in physicians who will use this treatment strategy for most of their MM patients.

Final Thoughts

Quick polls are a fast way of measuring expected acceptance of clinical data post major medical meetings, and perhaps can be used to make some assumptions about adoption amongst providers. In today’s information hungry environment, the speed at which these polls can be conducted and analyzed can be advantageous for market planning and “pressure testing” acceptance of data amongst key stakeholders.

June 21, 2010 - 10:06 am Posted in Featured comments0 Comments

By David Guy

This past ASCO in Chicago was something like the 18th or 19th one that I have attended, and it has grown from a few thousand physicians to this hectic weekend with over 25,000 attendees. When I first started in this industry, there were maybe a dozen chemo agents for the treatment of all cancers and now there are so many ibs and mabs I have trouble keeping track of them all. It could be that I’m getting old but thank goodness for Google and OBR Radar. Despite the advances in oncology and the number of new products approved there have been remarkably few products that have made a significant difference for patients with metastatic disease. We still consider an improvement in overall survival (OS) in terms of weeks or a few months a major treatment advance. Hence, a huge unmet medical need and opportunity exists for any new treatment that can improve upon the efficacy of existing regimens. The search for new rising stars is the most exciting part of the meeting for me. They also represent investment opportunities.

For this year, I think without question the data demonstrating that ipilumimab (BMS) can improve survival for melanoma patients by almost 4 months was the biggest news. Not only because it is the first treatment that has improved survival in a phase 3 trial for this patient population, but also that it works by activating the immune system. What also struck me is the significant effect maintenance use of a monoclonal antibody can have on patients. Results from the PRIMA study evaluating Rituxan® maintenance therapy in untreated follicular lymphoma, and data from the GOG-0218 trial evaluating maintenance Avastin® in first-line ovarian cancer were both positive.

There were several worthy rising stars coming from smaller companies. The most notable, are the results from Ziopharm’s (ZIOP) phase 2 PICASSO trial in which 67 soft tissue sarcoma patients were randomized to receive doxorubicin + palifosfamide or doxorubicin alone. The results appear pretty remarkable with the initial analysis of median PFS demonstrating a hazard ratio of 0.43 (P=.019) in favor of the palifosfamide arm in a very difficult to treat patient population. However, the stock took a significant fall today from $4.85 to $3.52 when the company announced that the FDA is rejecting PFS as an adequate endpoint for an SPA—ouch. Presumably the agency wants a survival endpoint. The company has reported a favorable survival trend in the phase 2 data but there is certainly more risk in the stock now.

Sunesis (SNSS) reported promising phase 2 studies of their agent voreloxin in patients with AML. I was particularly impressed with the high complete response rate (CR) in 69 refractory patients: 17 of the 20 responding patients achieved a CR. Encouraging results were also reported from phase 2 studies in first-line AML and refractory ovarian cancer. This is an interesting stock to watch, but I would caution investing in it. Why? In short—no control arm. It is very difficult (at least for me) to get a clear picture of how this patient population would respond receiving standard chemotherapy. I do not understand why companies choose not to conduct randomized phase 2 studies in this day and age.

Another interesting ASCO story is that of Delcath (DCTH)—the manufacturer of a proprietary system called PHP (percutaneous hepatic perfusion) which delivers chemotherapy to isolated organs. A phase 3 study of PHP was conducted in 93 melanoma patients with liver metastasis who were randomized to receive high dose melphalan with the PHP system or the physician’s choice of Best Available Care (BAC). Hepatic-PFS was the primary endpoint. Median H-PFS was 245 days in the PHP arm vs. 49 days in the BAC arm (P<.001).

Based on the initial reporting of these results on April 21st, DCTH stock rose to a 52-week high of $16.45 and was at $14.65 the Friday of ASCO. The company also reported that the OS was 298 days in the PHP group vs. 124 days in the BAC arm. After the above results were presented at the meeting, their stock fell to $10.83 at the close on Monday. What happened?

The presentation reported that OS was not statistically significant, but also noted that most patients in the BAC arm eventually crossed over to PHP. A debate then raged in the blogosphere about what this all means. DCTH has stated that H-PFS is in their SPA agreement with the FDA. Will the lack of significant OS put the approval at risk? It appears that this question is the basis for the stock falling. It is not surprising that OS was not significant because it was a secondary endpoint that the trial was not powered to detect—H-PFS was the primary endpoint.

Since DCTH’s SPA with the FDA is based upon H-PFS as the primary endpoint one would expect that approval will be likely—but not so fast. For the FDA to approve PHP with a single trial, the results must demonstrate a clear benefit. In my experience this means the primary endpoint must meet a P<.01—which H-PFS exceeds in this trial. However, will the agency continue to view H-PFS as predictive of a significant clinical benefit for these patients when faced with no survival benefit? From what I have read, the symptoms and complications of liver metastasis are very severe and an extended H-PFS should be a significant clinical benefit to these patients. The drop in the price of DCTH stock may represent a buying opportunity.

The ASCO meeting this year certainly was not disappointing and I will discuss more rising stars in my next post. Please send your questions and comments to davidguy1@gmail.com.

David is a veteran of the cancer business with 15+ years of experience commercializing several well known oncology therapeutics. He is currently a consultant and lives in San Diego.

June 14, 2010 - 11:06 am Posted in ASCO Conference Coverage comments0 Comments

By Nancy Ciancaglini

Photo of McCormick Place

As is the case every year at ASCO, in spite of 4,000 plus studies generated in time for the meeting there are a handful of clinical news stories that really stand-out and grab the attention of researchers, MDs, analysts/investors, and the media. Below, OBR presents a quick overview of what we consider to be the top ten clinical news stories from ASCO 2010. While they correlate pretty well, we usually see a slight difference in what the biggest media stories are and what is most read in OBR daily. To view the most read stories visit the OBR daily News Pulse and find out what others found most interesting at this year’s ASCO.

# 1: Bristol Myers-Squibb’s ipilimumab, a drug designed to enhance the body’s immune system, demonstrated a significant improvement in overall survival in previously-treated advanced melanoma patients in a Phase 3 study. Patients taking ipilimumab lived an average of 10 months compared with 6.5 months for those in a comparison group.  (Takes the # 2, # 3, # 5, and # 10 spot in the OBR daily News Pulse)

# 2: In two separate trials, Bristol-Myers Squibb’s Sprycel and Novartis AG’s Tasigna provided newly diagnosed patients with chronic myeloid leukemia (CML) with quicker, better responses as first-line therapies than the gold standard Gleevec, pointing to more favorable long-term outcomes for CML patients. (Figures in the # 2, # 3 and # 7 stories in the OBR daily News Pulse)

# 3: Following front-line therapy with Roche’s Rituxan and chemotherapy, Rituxan maintenance was found to reduce the risk of disease recurrence by 50% in patients with newly diagnosed follicular lymphoma, based on results from the PRIMA study.

# 4: In the Phase 3 GOG 0218 study, adding Roche’s Avastin to initial chemotherapy treatment, and then using it as maintenance therapy in women with advanced ovarian cancer, demonstrated a 39% improvement in the likelihood of women living longer without the disease worsening compared to chemotherapy alone. (Featured in the # 2 most read story in the OBR daily News Pulse)

# 5: In a head-to-head Phase 3 trial of Amgen’s denosumab and Novartis AG’s Zometa, denosumab delayed by 18% the risk of fractures and other bone complications in men with advanced prostate cancer compared with Zometa, the current standard of care for treating cancer patients whose disease has spread to the bone. (Included in the # 2 most ready story in the OBR daily News Pulse)

# 6: Women with advanced breast cancer given Eisai’s experimental chemotherapy drug, eribulin mesylate, derived from a sea sponge, lived longer than those treated with standard cancer therapies—women taking eribulin lived an average of 13.1 months compared to 10.7 months for those receiving conventional cancer treatment.

# 7: In a Phase 2 study, Pfizer’s crizotinib (PF-02341066) reduced tumors in 57% of patients with a rare form of lung cancer caused by a defective ALK gene and stopped the progression of the disease in 87% of patients, providing further clinical evidence in support of personalized cancer treatment.

# 8: In surprising results, Eli Lilly & Co. and Merck KGaA’s Erbitux, successful in treating metastatic colon cancer patients with normal KRAS, failed to prolong survival for patients with early-stage colon cancer (adjuvant) when added to standard treatments. After 16 months follow-up, patients taking Erbitux were actually slightly less likely to survive, with 82% still alive compared with 87% taking chemotherapy alone. (The # 6 most read story in the OBR daily News Pulse)

# 9: Delcath System’s percutaneous hepatic perfusion (PHP) drug delivery system with melphalan extended survival much longer for melanoma patients whose cancer had spread to their liver—patients lived 245 days versus 49 days on best available care.

# 10: In the first, definitive Phase 3 study to show results for patients with advanced medullary thyroid cancer (MTC), AstraZeneca PLC’s vandetanib significantly extended progression free survival (PFS), demonstrating a 54% reduction in the rate of progression compared to placebo.

The July issue of Oncology Business Review will feature more in depth analysis of these important study results. Stay tuned for more.

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