The Big Red Biotech Blog

Why do some cancer drugs work and others don't?

The news yesterday from Amgen that panitumumab (Vectibix) failed in Head and Neck cancer got me thinking.  Why did it fail where cetuximab (Erbitux) succeeded? They're both monoclonal antibodies to EGFR, so that makes it rather interesting.

via www.pharmastrategyblog.com

Maybe Time to Cry Over Spilt Telaprevir!

Last week I opined that Lilly wouldn't be engaged in much hand wringing over prospect of giving up its rights to Telaprevir to Vertex Pharmaceuticals back in 2002.  Today, Vertex announced more Phase III trial results for the drug -- and claim that when combined with standard therapies it is able to reduce treatment time for hepatitis C infection of the liver by 50%, i.e. by 24 weeks. Largely, this data is supportive of the Phase III trial data the company released back in May -- but it is more good news for Telaprevir.  Analysts believe this should be a boost for the stock but are uncertain what market reaction will be. It may be a buying opportunity.

See stories from Xconomy, Seeking Alpha, and Fierce Biotech.

Posted by Bruce Lehr August 10th 2010.

Feds Probe Payments In Overseas Drug Trials

Ed Silverman's Pharmalot blog had this post this morning. The US Justice Department and the SEC will be looking into relationships of pharmaceutical companies with foreign goverments.  As reported over the past several weeks, clinical trial work is increasingly being done outside the US for drugs that ultimately end up being marketed in the US.  This puts additional pressure on the FDA to try to monitor these trials.

Feds Probe Payments In Overseas Drug Trials // Pharmalot.

 As described last week, a new Senate bill will among other things give the FDA more oversight and enforcement powers relative to foreign drug trials, and increase its resources for oversight.

Posted by Bruce Lehr August 9th 2010.

Seattle Genetics Readies for Busy Clinical Season this Fall

Between September and October this year, Seattle Genetics is expecting results from up to 3 clinical trials -- each of which could result in an NDA filing. Two of the trials are with its lead compound SGN-35, brentuximab vedotin, an antibody drug conjugate. SGN-35 is in clinical trials for the treatment of two CD30 targets -- refractory Hodgkin's Lymphoma and anaplastic large cell lymphoma (ALCL).  Takeda's Millenium paid $60 M upfront with up to $230 M in milestones for SGN-35 earlier in 2010.

Seattle Genetics other lead candidate is SGN-33, lintuzumab, directed against CD33 found in AML and MDS cancer cells. SGN-33 may give these patients another treatment option besides cytarbine which is not tolerated well in patients over 65.  Celgene's competitive product Vidaza is currently expected to reach sales of $500 M for these applications -- indicating good potential for SGN-33 too.

Read full report in Seeking Alpha.

Posted by Bruce Lehr August 6th 2010.

 

Favorable Results More Likely Published When Drug Trials Funded By Industry

Favorable Results More Likely Published When Drug Trials Funded By Industry.

I saw versions of this headline several times yesterday and was able to ignore.  Today, I just can't fight it anymore and can't resist commenting. 

Let's see now.  Getting paid to do a study results in positive results more often than not for the group funding the study.  Duh!

Who'd thunk that paying for results would pay with results?

Posted by Bruce Lehr August 5th 2010.

 

Merck's Boceprevir Competition for Telaprevir

In relation to the previous post, one mustn't forget there is competition out there as well. There is no guarantee that even if you get your drug to market that it will become the dominant player.  Fierce Biotech reports this morning that Merck's boceprevir hit all its primary endpoints in its two latest phase III trials.

So now it will be a bit of a race between boceprevir and telaprevir for dominance in the hepatitis C treatment market.  Telaprevir has also performed very well in its clinical trials and may have fewer side effects (like anemia) than boceprevir. 

Nevertheless, the market will decide which drug prevails.

Posted by Bruce Lehr August 4th 2010.

Can't Cry Over Spilt Telaprevir

This post by Ryan McBride came from the Xconomy blog.  It recounts history of telaprevir -- Vertex Pharmaceuticals' treatment for hepatitis C -- as it nears approval. Analysts project that it could have sales in excess of $2 B per year if it does get market approval.

It turns out that Lilly helped develop the drug in its early days (late 90's) but gave up all its rights to the drug in December 2002. Is Lilly regretting the decision?  I doubt it.  This scenario must have played out many times within the drug industry. You are always placing some bets when deciding which compounds to take forward. 

Sometimes you get the Bear.  Sometimes the Bear gets you. I'm sure Lilly has had other successes with projects that it has taken forward.  One never knows what trade offs have to be made internally to bring one candidate or another forward. Besides, Lilly didn't have all the development costs for this product over the past 8 years either - while Vertex has a reported $2.8 B into the drug.  It's just another day in the life of the drug business.  Turn the page and move to the next project.

Posted by Bruce Lehr August 4th 2010.

FDA Panel: Brilinta 7 Aspirin 1

An FDA advisory panel voted today 7-1 to recommend that AZ's potential blockbuster blood thinner, Brilinta, be approved by the agency in September.

FDA Panel OKs AstraZeneca’s Brilinta Blood Thinner // Pharmalot.

Brilinta will become a direct competitor for Sanofi-Aventis' and BMS' Plavix - the world's second leading selling drug at more than $9 B annually.  Brilinta, if approved in September, is expected to easily top $1 B by 2014. 

Panel members issued their approval even as they struggled to explain why the 1400+ patients, out of the more than 18,000 patients tested worldwide, did not respond markedly different than US patients on aspirin.  Higher average aspirin doses in the US were posited as one possible explanation but certainly this was  not conclusive.

On balance, the panel recommended approval based on the sterling results seen in the rest of the world when comparing Brilinta to Plavix where heart attack, stroke or cardiovascular-related death dropped to a rate of 9.8 percent as compared to 11.7 percent after one year.

We await the news of the FDA in September.

Posted by Bruce Lehr July 28th 2010.

Chasing Alzheimer's Mega-blockbusters

Fierce Biotech has reported the past few days on Alzheimer's programs of several Big Pharma companies including Lilly and a group consisting of J&J/Pfizer/Elan.  Alzheimer's remains a hot-bed of exploration for better therapies, as there really are no good choices.  This is seen as a potential gold-mine for the first companies to come to market with any drug that has a measurable benefit in delaying key memory loss symptoms. Some analysts have predicted annual sales potentials of $5 B or more for such therapies.

Elan et al's bapineuzumab has shown promise (J&J has invested $1 B) in Phase II trials in targeting amyloid-plaques and in also lowering the level  of the toxic tau protein. Both features are thought to be important although there is no well described mechanism of their involvement.  Results of Phase II have been encouraging enough to push toward Phase III.

Similarly, Lilly's semagacestat and solanezumab drugs are also targetting amyloid plaques via different pathways. The company is no in the process of recruiting late stage trial participants - over 1000 patients for each study.

Again, the payoff for a successful Alzheimer's therapy is expected to be huge - so the race is on.

Posted by Bruce Lehr July 14th 2010.

Roche Seeks FDA Nod for T-DM1 and files BLA

As reported in Fierce Biotech and Xconomy (below), Roche reviewed its encouraging clinical results with T-DM1 and filed a BLA with the FDA. 

Genentech Seeks FDA Nod for T-DM1.

T-DM1 is the next generation of Roche's Herceptin conjugated to a cytotoxin for the treatment of breast cancer in women who are Her2 positive and have been treatment resistant.  T-DM1 is an antibody conjugated drug (ADC) developed with technology coming from a partnership with Immunogen.  T-DM1 is xconsidered to have a chance to be another blockbuster in the cancer arsenal.

With an accelerated review, Roche could get marketing clearance in as little as 6 months for treating advanced breast cancer. The drug has performed so well in Phase II trials in shrinking previously treatment resistant tumors that expedited approval is considered a real possibility.

Posted by Bruce Lehr July 7th 2010.

How do you spell writer's faux pas?

T-A-N-E-Z-U-M-A-B! Ouch!

Earlier this week, I touted this drug as likely to receive expedited approval and be the first biologic pain reliever to ever be approved.  Now, a few days later, Fierce Biotech reports that Pfizer has been forced to suspend clinical trials.  The drug has caused serious enough side effects in some osteoarthritis patients as to require them to seek joint replacement surgery.

The Pfizer news release can be accessed here.  Pulling a potential winner off the table like this really is a PAIN!

Posted by Bruce Lehr June 24th 2010.

First Supply Chain, Now Drug Trials Under Scrutiny

Undoubtedly, we're all critically aware of quality issues with supply chain for raw materials, excipients and even APIs - particularly from developing countries like China.  Clearly there is work to do across vendors to raise quality standards and oversight for critical materials to be used in drug (& food) manufacturing.

Now we have a new HHS report that calls into question clinical trial results as well from some of these developing areas - China and Russia in particular were identified.   It likely is not a surprise that clinical trial work is being outsourced to areas besides the US and Western Europe due to much lower costs. It may be a surprise to what extent this is occuring.  The HHS report found that 80% of all drugs approved in the US in 2008 relied on some foreign trial data, 78% of all study enrollees were at foreign sites, and 10 new drugs had no US derived data at all. 

This is seen to be a dangerous situation by some.  Congresswoman Rosa DeLauro of Connecticut states, "By pursuing clinical trials in foreign countries with lower standards and where FDA lacks oversight, the industry is seeking the path of least resistance toward lower costs and higher profits to the detriment of the public health."

Not too comforting if it can be taken at complete face value.  It would be nice to see exactly what quality corners are being cut to assess that portion of the claim. Aparently, there is less liability to worry about in these countries and informed consent is more "cloudy" shall we say.

One of the problems with cost is that many US and Western clinical investigators don't want to do trials anymore - trial investigators have dropped by 5.2 and 6.1 percent respectively in each geography. While numbers have blossomed in Eastern Europe (up 16%), Asia (up 12%) and Latin America (up 10%).   US investigators want to make money and don't want increased reporting requirements - especially income disclosure requirements imposed by new sunshine legislation - 24% say they are less likely to participate in a trial as a result of financial disclosure.

Hmmm!  Sounds like we're not going to be seeing a change in this trend anytime soon. 

By the way, PhRMA disputes that there is any difference in regulatory standards for clinical trials regardless of location. See PhRMA website for the complete statement.

Posted by Bruce Lehr June 23rd 2010.

Roche hits pothole with taspoglutide

Fierce Biotech reports that Roche has suspended its trial with the highly touted diabetes drug taspoglutide. Only a few months ago, Roche CEO Severin Schwan was highlighting taspoglutide as a best in class drug during Roche's pipeline review. 

Roche expects Taspoglutide to be a blockbuster that will outcompete Amylin's recently approved Bydureon. However, the late stage trials have now been suspended for an expected 18 months due to patients experiencing hypersensitivity reactions, stomach pain, heart and respiratory symptoms.

Roche's plans for filing in 2011 are gone and the company may now have to wait until 2014 for approval (if ever).  The delay has caused industry analysts to revise sales for this drug in 2014 down from $2.8 billion annually to a mere $490 M.  That's a big bump in the road.

Posted by Bruce Lehr June 18th 2010.

How do you spell relief?

Soon it may be T-A-N-E-Z-U-M-A-B! 

Pfizers new biologic for treatment of pain associated with osteoarthritis.  The new therapy just hit its endpoints in a phase III study with 690 patients who did not receive sufficient relief from NSAIDs or Cox-2 inhibitors.

Results are so good that Fierce Biotech reports that this drug is now the leading candidate to become the first mAb (and large molecule) to be approved for pain relief.  This news has got the folks at Pfizer and its partner Xoma feeling no pain.

Posted by Bruce Lehr June 18th 2010.

Concensus View from ASCO - or Not?

Many observers, see Fierce Biotech and Forbes blog as examples, have declared that Bristol-Meyers Squibb and Pfizer were the really big winners at ASCO. BMS reported sterling results with its new cancer immunotherapy drug ipilumumab for the treatment of stage 4 melanoma patients - the drug increased mean survival from 6.4 to more than 10 months which by all accounts was impressive. Some analysts are projecting this to be a greater than $1 B a year drug.

Pfizer also reported good results for its lung cancer drug, crizotinib, which stopped disease progression in 87% of patients it was tested on.  The drug is designed to be used with lung cancer patients exhibiting the ALK gene (5% lung cancer patients), as learned by Japanese researchers.  The drug could hit $800 M in annual sales. 

Other honorable mentions for the show include Roche for a very positive study with Avastin's use in the treatment of ovarian cancer.  The results suggest the drug has a future in maintenance dosing for this and possibly other cancers. 

Amgen's Prolia was also deservedly singled out.  It received FDA approval recently for the treatment of osteoporosis but is also looking for an indication in the treatment of bone loss in other cancer patients.   Should it achieve the latter approval, some analysts are projecting peak sales as much as $3 B per year.

The above describes the general consensus in the press coverage of ASCO.  However, as always, there are other with differing or more tempered views, examples include pieces from the Pharmalot blog, the Forbes blog, and yet a third offering from the Forbes blog.

The first two blogs discuss BMS' unusual study design in the ipi melanoma trial. BMS chose to compare its drug to a vaccine instead of to a placebo or other treatment standards (there aren't many).  This could make it difficult to predict how the FDA will interpret its application for approval. One big question is whether the control vaccine had any negative effects itself - thus making it a poor control.  BMS seems confident that it has vetted this possibility and is confident in its positive results. And it better be, as BMS has several other cancer immunotherapy candidates in its pipeline acquired from Medarex for $2.3 B.  Even the skeptical analysts on BMS chances of easy approval were increasing their annual peak sales estimates up to a range from $700 M - $1 B. 

The last blog post from Robert Langreth acknowledges the apparent success of the BMS and Pfizer drugs, but points out that there were a lot more failures reported than big winners.  This included failed trials involving Pfizer's Sutent (breast cancer), Roche's Avastin (colon cancer), and Lilly/BMS Erbitux (colon cancer).  Big Pharma still hasn't found a fool-proof way to select and develop cancer therapies - and Langreth questions whether there is a rush to trial before the biology is really understood. Even treating patients at earlier stages (less advanced) of cancer did not always pan out - see colon cancer.  

So in the end, it is still a mixed bag of cancer successe.  It is clear there may be some significant new therapies approved with enviable sales projections.  It is also true that there have been some dismal trial failures and a need to keep refining the way we go about developing and testing new therapies.

Posted by Bruce Lehr June 7th 2010.

Cancer Immunotherapy Breaks Through the Wall

Good news for cancer patients.  Another immunotherapy approach has succeeded in showing benefits toward extending life for adavanced cancer patients - this time it is BMS' drug ipilimumab for the treatment of melanoma.  Ipilimumab's most recent clinical results, announced at the ongoing ASCO meetings, have been viewed as outstanding by those in attendance and have even been characterized as a "paradigm shift" for the future treatment of melanoma patients.  

Coupled with last month's FDA approval of Dendreon's Provenge, for the treatment of prostate cancer, we now have two drugs that validate the immunotherapy approach to treating cancer.  Both drugs work similarly in that they turn off the production of CTLA4 by the body.  This allows immune killer cells to mount a more spirited attack on the cancerous cells.  It feels good to break through that Wall.

 

Based on this successful use of the immunotherapy concept, we can expect to see this applied by others to the treatment of cancer.  BMS will now attempt to establish that the treatment can be applied to earlier stage melanoma patients.  But, the company also believes that the treatment potentially can be applied to all cancers - and will be pursuing trials in lung cancer patients as well.

With this success, we can expect more competition in this area and for this approach. BMS is well down this path already having picked up several other cancer immunotherapy candidates through its purchase of Medarex.  GSK is also working on an immunotherapy drug to be applied to lung cancer, and Pfizer has its own ipilimumab version called tremelimumab.

Regardless, we now have another new approach to try on cancer.  Coupled with some of the new ADC approaches, we should continue to have a lot of activity in the development of cancer therapies - further justifying the analysts predictions that this will be a fast growing area for biotech drugs in particular.

Posted by Bruce Lehr June 6th 2010.

Merck Networks Cancer

Fierce Biotech reported yesterday on Merck's announcment that it has established a global network of research centers to attack cancer.  The idea is to create new approaches to increase speed of discovery of cancer drugs and vaccines.

The part of the report that caught my eye was Merck's citation of an Institute of Medicine study that concluded that it took more than 2 years to get the "typical" cancer study designed, approved and activated.  And my favorite stat - only 50% are ever completed!  I guess that is an example of being half-fast.

Merck is trying to speed up the process by recruiting participating centers of excellence with core strengths in biomarkers, information technology and adaptive study design.  The new Merck network stretches from Brazil to Norway and only time will allow us to assess whether this network model will actually speed the process.

But I give Merck kudos for trying something different in creating the Network. I guess they got Mad as Hell and Just Couldn't Take It Anymore with slow or non-completed trials.

 

Posted by Bruce Lehr June 5th 2010

Not Sure Who is Fastest Follower but Pioneer Looks to be Roche

I made a post several days ago, that discussed one of the surest successful business models is to be the best Fast Follower (BFF so to speak) in a market.  I didn't say who I thought that might be - but I would give a nod toward Teva as having a good chance to claim the title.

However, in the same post, pioneers were also discussed briefly.  Pioneers have it tougher in many respects as they can often be the ones to open up a market but then can lose out to the Fastest Follower coming from behind.  Don't look back, someone might be gaining - as Satchel might say.

Nevertheless, Pioneers can also win and come to dominate the market as first in.  Going wire to wire so to speak.  With regard to the pioneer slot in the pharma world, I'm leaning toward Roche at this point.  Not only did they have a reasonable pipeline themselves, they greatly solidified it with their acquisition of the final 44% of Genentech last year.

In March, Roche's CEO reviewed their pipeline for analysts.  He detailed that Roche expects to launch as many as 6 new products by 2014 and may also file up to 35 line extensions on existing products.  All of the 6 products were characterized as "best in class" or "first in class".  Most continue to build on Roche's strong oncology position.

In yesterday's Seeking Alpha, Jason Chew wrote about Roche's focus toward personalized medicine (personalized oncology) and their relatively unique position as both a strong pharma/biopharmaceutical house and a diagnostics company. Currently, 20% of Roche's sales come from its diagnostics holdings. Roche used that strength in the past to combine a diagnostic test for the Her2 gene to target the patients who would most benefit from its blockbuster Herceptin (trastuzumab).

Now Roche appears to be using this same strategy with other drugs in development in its pipeline.  Its B-RAF compound, PLX4032, is in pivotal trials for the treatment of melanoma patients.  But not just any melanoma patients - Roche is able to target those 60% of melanoma patients with the V600E B-RAF mutation. It turned out in phase I trials that 70% of patients with V600E experienced tumor shrinkage when treated with PLX4032 while those without the mutation showed NO RESPONSE.

Soooo - Roche is working on launching both PLX4032 and the B-RAF V600E diagnostic test in tandem. This helps trial design, recruitment, and ultimately requires fewer patients in the trial. It fairly stacks the deck toward success of the trial as patients most likely to respond are the ones being treated.  What a concept?

Roche is advancing its drug portfolio, its diagnostic portfolio and is entering the sphere of personalized medicine in big way.  That sounds like a pioneer.

Posted by Bruce Lehr June 3rd 2010.  

EU approvals for Amgen’s drug Prolia (denosumab)

Amgen received news today that its drug denosumab, branded Prolia, received its first approval in the EU for the treatment of osteoporosis in women and bone loss in men following hormonal therapy for prostate cancer.

EU approvals for Amgen’s osteo drug Prolia - Pharma Letter.

Prolia has been viewed as an important drug to the company's future earnings and this must be viewed as good news back in California.

Posted by Bruce Lehr May 28th 2010.

Stop Picking on Genzyme! Slight Tip of the Cap for Lumizyme.

Ok, for a day or so I will not harp on the negatives associated with its recent manufacturing woes or battles in the boardroom.

Today, I'll provide a small acknowledgement of success with the word of FDA approval for Lumizyme (alglucosidase alpha) for the treatment of Pompe disease.

So from me and the Bambino.   

Posted by Bruce Lehr May 26th 2010.

Novo Nordisk's Victoza® (GLP-1 analog) cardiovascular outcomes trial

Novo Nordisk's Victoza is the latest GLP-1 analog to be approaching the market for the treatment of type 2 diabetes.  See previous posts on GLP-1 rivals Amylin/Lilly, Roche, and GSK.  

In this trial, Victoza will be studied for its cardiovascular safety in treatment of type 2 diabetics, since there is a well established link between cvs disaease and type 2 diabetes.  This trial will attempt to show that use of Victoza will lead to better cvs outcomes in these patients corroborating a prvious study of Victoza (liraglutide).

Novo Nordisk partners with international scientific community for Victoza® cardiovascular outcomes trial.

Posted by Bruce Lehr May 7th 2010.  

Genzyme Pushes Back in Board Battle Royale

Here is an update on the Genzyme battle for the board as reported in Cliff Mintz's BioJobBlog.  Genzyme has returned fire by authorizing a significant stock buy back and divesting non-performing business units (assets of sorts) in response to Icahn's overtures.

Genzyme Pushes Back : Bio Job Blog

Posted using ShareThis by Bruce Lehr May 7th 2010

Clarion Call - FDA Approves Dendreon Provenge!

As very very recently reported in the Pharmalot blog,  the FDA has just approved Dendreon's Provenge as the first vaccine for prostate cancer!  After almost 3 years in the waiting in agency - the good news is out for Dendreon stockholders and share price has jumped 15%.

Posted By Bruce Lehr April 29th 2010.

Alkermes Must Also Be Counting on Swift Bydureon Approval

Last week, I posted on Amylin's vigil for a swift approval of Bydureon by the FDA following resubmission of requested information.  This drug represents a partnership between Amylin, Eli Lilly and Alkermes to bring it to market as a breakthrough 1x per week treatment for type II diabetes.

As reported in Xconomy today, Alkermes too must be eager to see this drug gain approval, hit the market and start cranking sales. It seems Alkermes, stands to gain an 8% royalty on first 1st 40 M units of Bydureon sold annually (at current prices approx $2 B in sales). That's $160 M in intial royalty potential and is some serious cash for Alkermes.

“We’ll be making profits from the first vial of sales,” says CEO Richard Pops. “If it’s a $5 billion product, we’ll make hundreds of millions per year. With no capital investment. It’s pure profit.”

Alkermes inked the deal in 2005, and is in this position as it claims it was the only company capable of delivering the chemistry to make Bydureon (exenatide) stable and effective in the blood stream for 1 week.

Now, all that remains is to see how swiftly Alkermes can start taking its profit.

Posted by Bruce Lehr April 26th 2010. 

Pass/Fail Grades from the Clinic

 Let's look at drug performance in the clinic today to see which pass and which fail in their bid for approval as reported in GEN.

Pfizer's Sutent for liver cancer - FAIL

OSI's Tarceva for maintenance of NSCLC patients - PASS by FDA

GSK's Duodart for BPH - PASS by European regulatory clearance

Novartis' Joulferon (albinterferon alfa-2b) for chronic HCV - FAIL after EU feedback and Novartis pulls MAA.

Cell Therapeutics Pixuvri for treatment refractory NHL - INCOMPLETE by FDA and more clinical data needed

Merck Serono's Erbitux for 1st-line treatment of colorectal cancer - PASS by Japanese regulators.

Posted by Bruce Lehr April 23rd 2010.