The Big Red Biotech Blog

FDA and USP to Hook Up on Monographs (& such)

The PharmaTech Talk blog recently had an interesting post on the FDA's plans to have greater collaboration with USP.  FDA Commissioner, Margaret Hamburg, made these comments at the most recent USP Convention.

Commissioner Hamburg stated 3 objectives for the collaboration between the two bodies:

"First, Reference Standard Candidate Assessments will test standard candidate materials that are controlled substances.

Second, to combat economic adulteration, FDA and USP will exchange information on hand-held device applications designed to screen drugs for adulteration or contamination and will explore ways to integrate the requirements of those new technologies into USP’s documentary standards.

And third, FDA will assist in the development and modernization of USP monographs providing enhanced tests and assays to better assess and characterize drug ingredients and products."

This looks like a good approach to me.  I like the agency's new priority toward collaboration with outside experts.  This willingness to collaborate actively with USP seems similar to the FDA's earlier announcement this year that it would seek more active discussions with experts within the NIH to help speed drug application reviews.  This seems like a common sense approach to combine expertise from two sources to get a more wholistic picture and better result. 

With the drug adulteration issues that have arisen in China, and elsewhere, in past couple of years, it makes sense to tap and share expertise to use resources better and to institute best practices wherever possible. I like the USP collaboration's emphasis in looking at hand held technology to better detect contamination or adulteration.  Certainly, there is always room to look at imporving the science and analytical techniques spelled out in the monographs - there is more rapid evolution in testing and a greater need to stay current to meet the global regulatory challenges.  Especially, with the vast increase in volumes, shipments and nations involved in the supply chain.

This move is consistent with what our customers have spoken to us about in regard to improving testing around raw materials used in biopharmaceutical processing. Effectively the 3 FDA areas of emphasis with USP, will help to improve raw material characterization, and will do so in way that is relevant to the end users intended applications.  This will also be in alignment with the regulatory process.  This can only help move us toward a more secure global supply chain with more harmonized criteria for assessing quality.  This should lead to safer and better raw materials with consequent better final drugs coming out of these processes. 

I applaud this idea.  I'd like to see it move rapidly toward collaboration and implementation.  There may also be an opportunity here to tap into private company expertise and subject matter experts.  This could build upon the planned FDA-USP collaboration and go even further to incorporate testing standards, technologies and methods that are especially relevant to the industries and supply chains being regulated.

Posted by Bruce Lehr April 30th 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.

Counting CRO's in China - One Upsmanship!

No sooner did Charles River report of its $1.6 B deal to acquire Wuxi Apptec's CRO business hit the street, PPD announced the opening of its new vaccine research center and claimed title of biggest CRO in China.  See Fierce Biotech.

PPD opened its center in Taizhou China Medical City to enable it to conduct the world's largest vaccine trials but with shortened recruitment times due to easy access to study participants. The new center supports the fast growing vaccine market (> 20% CAGR).

Simon Britton, PPD's VP of clinical development for Asia Pacific, stated "Our strong expertise in vaccine clinical research and large presence in China make us well positoned to help our clients ensure adherence to global standards while addressing unique requirements for monitoring vaccine studies"

That's a lot of investment, and a lot of CRO activity in China for this week - or any week.  But, as explained in FierceBiotech's story on China's CRO appeal, China's local authorities are willing to aggresively work with new businesses to meet their needs and make it happen.  This according to Charles Rivers outgoing Chris Perkins.

China is less expensive to build in, has large, less expensive talent pools, far less expensive animal models, and regulators who want to help business. They also don't have any animal rights activists to harry labs and perhaps drive them underground as has happened in EU & US.

That's a number of good reasons for Big Pharma companies to do business with CRO's located in China - but who's counting.

Posted by Bruce Lehr April 28th 2010.

Chas River Plots Fastest Way Through Pipeline - via China as the CRO Flies

 Charles River Laboratories, Wilmington, MA, announced yesterday that it was acquiring Shanghai-based Wuxi Apptec Tech for $1.6 B in cash and stock. This apparently represents the largest foreign takeover of a Chinese company.

Charles River, with $1.2 B in 2009 sales, will add $270 M in sales from Wuxi, 4000 employees, and over 1.8 M sq. ft. in lab space in China.  Wuxi also has 3 significant operations in Atlanta, Philadelphia and St. Paul, MN with R&D and manufacturing capability.

Chas River also picks up state-of-the-art, large animal testing capability, including monkeys, and gains access to testing facilities in Shanghai, Suzhou and Tianjin in China - where laboratory and labor costs are a bargain.

Jinsong Du, an analyst at Credit Suisse, states "This is a vote of confidence that China will be the main location for drug R&D outsourcing in the future." He also notes that Chas River gets to take out a competitor with this acquisition.

Because major new drugs may require 15 yrs of development time at a cost exceeding $1.5 B, a growing number of Big Pharma are trying to find ways to cut costs and speed development through the pipeline. Many are moving their research and development, manufacturing and clinical trial work to places like India and China due the current cost advantages.

"This transaction revolutionizes the contract research landscape by creating the only global contract research organization, or CRO, to fully offer integrated research and drug development services from molecule creation to first-in-human testing," said President & CEO James C. Foster of Charles River. Charles River can now offer services in the US, EU and China. Foster says "...many of our clients consider China to be the new frontier for drug development."

The deal likely couldn't come too soon for Charles River as they reported Qtr 1 earnings fell well short of expectations and were 22.4% below last year. Sales were down to $297.4 M in Qtr 1 2010 versus $301.5 M in Qtr 1 2009.

Financial details of the acquisition can be found here and were obtained from Charles River's website.

Download Charles_River_WuXi_Slide_Presentation

 

Posted by Bruce Lehr April 27th 2010

Raw Material Detectives - Case #1 The Crystal Shift

 It was a dark and gloomy night.

Our Customer contacted the Global Technical Service (GTS) group with complaints of poor product performance. The GTS squad logged the report into the complaint handling system. 

The customer, a large, US-based biopharmaceutical company, reported that they were having problems with their custom CHO medium - and were observing growth and productivity fluctuations from lot to lot within their commercial process.  

An investigation began with GTS and quality assurance in a cross functional team that included members from supply chain management (SCM) and cell sciences and development (R&D).  A review of batch records listing raw material lots and vendors in the batches of media narrowed the list of potential culprits to 6 raw materials.

After extensive collaborative trouble-shooting, the Customer and GTS concluded that there likely was a problem with the L-tyrosine from a specific vendor that was included in the formulation.  Suspect was L-tyrosine 2Na H₂O.

The Investigative Team lined up 3 lots of L-tyrosine 2Na H₂O from 3 vendors for interrogation.  Vendor 1 was suspected as the supplier of the problematic material.  Vendor 2 and 3 were alternative qualified vendors for our line up.  We also included a positive control. CSD began its testing.

Analytical Testing

The suspect lot of L-tyrosine was tested side by side with lots from two other qualified vendors via several analytical methods.  The testing was performed to assure product identity and to allow the detection of impurities.

Reverse phase-HPLC (RP-HPLC)

Size-exclusion chromatography (SEC)

Ultra-performance LC-MS (UPLC-MS)

No significant differences were detected between the suspect amino acid, comparison vendor samples and controls via these methods.  No obvious impurities were detected.

Batch Record - Process Review

The manufacturing process flow diagrams were examined from the 3 vendors - suspect and alternatives.    Our first important clue - there was 1 process step difference from the others with the suspect vendor.

The Investigative Team decided to perform biological testing between the 3 different vendors to see if the suspect vendor's material would show biological variance.

Biological Testing

CSD tested 3 lots of L-tyrosine 2Na H₂0 from each of the 3 vendors in CHO-GS cells producing a control MAb.  CSD plotted growth curves and measured MAb productivity.

Cell growth curves generated with lots 1 & 2 of L-tyrosine from Vendor 1 at best reached only 88-90% of the average peak cell density seen for Vendors 2 & 3.  The worst performing lot 3 from Vendor 1 only reached 55% of the peak cell density seen for Vendors 2 & 3, and thus was also signifcantly worse performing than lots 1 & 2 from same suspect Vendor 1.

Download Tyrosine Cell Culture Data

Similarly, IgG productivity of CHO-GS cultures grown on medium containing suspect Vendor 1 lots of tyrosine was 12-63% lower than cultures grown on medium incorporating L-tyrosine from Vendors 2 & 3.

Download Tyrosine Productivity Data

Filtration Studies

Since the biological variance of the suspect material had been confirmed, one logical explanaton for the poor performance was a solubility problem with the L-tyrosine from Vendor 1 as compared to the other two vendors.  

The Investigative Team decided to run filtration studies.  Lots of L-tyrosine from the various vendors were filtered and the post-filtration amino acid concentration was calculated versus the expected yield. Vendor 1 material did not filter as well.  When cells were grown in medium formulated with different lots of L-tyrosine from the 3 vendors, there was a direct correlation found between the amino acid concentration remaining and the productivity titers in cell culture assays. The suspect L-tyrosine was not making it through the filters.

Download Tyrosine Filtration Data

Physical Property Analysis

SAFC owns a company called Pharmorphix that provides expert solid state chemistry services and specializes in pharmaceutics. CSD decided to have them analyze 3 lots of the L-tyrosine 2Na H₂O from suspect Vendor 1(bad lots) and Vendor 2 (good lots).

SAFC's Pharmorphix group performed 3 different analytical techniques:

X-ray particle diffraction (XRPD) to determine crystal structure.

Differential scanning chromatography (DSC) to determine melting points of the crystals.

Ion chromatography to allow quantitation of the Na⁺ ions.

Results for the XRPD analysis are shown below.  These results reveal there were distinct crystal forms between lots from Vendor 1 and Vendor 2.  What's more? Vendor 1 had different crystal forms between its own lots and multiple crystal forms existed in 1 lot - the very poor performing lot 3.  DSC also pointed to the suspect L-tyrosine having melting points that varied from the "good lots" and exhibited multiple melting points within the population of 3 suspect Vendor 1 lots. Suspect 1 was different.

Download Tyrosine XRPD Data

Case Conclusion

Evidence revealed differences in crystal structure between good lots of tyrosine and suspect Vendor 1 bad lots of tyrosine.  These structure differences likely led to the poorer solubility characteristics of Vendor 1 material. This in turn led to poorer filterability and lower concetrations of Vendor 1 tyrosine in the final medium post-filtration.  This resulted in the poorer growth and productivity observed in the CHO GS cells.

Why the difference in crystal structure?  Recall the batch record review.  Suspect Vendor 1 was using spray drying to prepare its final tyrosine product.  Vendors 2 & 3 were using tray drying.  We believe this led to the variablity in crystal structure seen with the Vendor 1 material. 

Corrective Action

SAFC Supply Chain Management and Quality Assurance shared the analytical findings of the CSD team with Vendor 1.  Vendor 1 was busted.

Vendor 1 at present has been removed as a Qualified Vendor of L-tyrosine to SAFC. Vendor 1 would have to go back through a qualification process with at least 3 lots of new material before it could potentially be qualified again. 

Case File: 04272010-01

Raw Material Detectives Case No. 1

Suspect: L-tyrosine 2Na H₂O

Charge: Poor solubility and decreased product performance

MO: Crystal form change due to spray drying process

Solution: Use qualified vendor 2 or 3; Suspect Vendor 1 disqualified pending results of any future requalification effort

Case Disposition: Case Closed with final vendor notification of investigation. Results are Crystal Clear.

Posted by Bruce Lehr April 27th 2010

 

 

 

 

SAFC Moves Toward Excellence

SAFC provided (as reported in PBR) more details on its planned creation of a dry powder medium milling Center of Excellence in its Lenexa, KS facility.  The $6.25 M expansion will provide for 3 manufacturing lines standardized on its continuous milling (CM) technology - and the plant will have the ability to scale up from development to pilot through commercial scale. 

This is part of SAFC's global facility strategy that will reduce its number of cell culture manufacturing facilities from 5 to 3 and create new Centers of Excellence for liquid and dry powder medium manufacturing and deciated animal-containing (ACC) and animal component free (ACF) manufacturing zones.  Centers of Excellence will be created in Lenexa, KS; St. Louis, MO; and Irvine, Scotland.

Posted by Bruce Lehr April 27th 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. 

More Drug Sales in Hong Kong With Better Economy

Business Monitor International has increased the forecast for the size of the pharmaceutical market in Hong Kong for 2019 - raising it to $1.53 B.  Currently the market stands at $988 M. By Asia market standards this represents a relatively modest CAGR of 4-4.5%. 

 

The healthcare sector in Hong Kong is reportedly developing rapidly, but I'm still surprised by lower growth estimate given the recent IMS report touting emerging pharma markets hitting growth rates from 14-16%. 

Posted by Bruce Lehr April 26th 2010.  

Raw Material Detectives - coming this week - Case #1

Visit the Big Red Biotech Blog this week for the first installment of the Raw Material Detectives.

This series is devoted to the mysterious misbehavior of raw materials in biopharmaceutical processing.

The investigation of the mystery.  And the solution to the Case.

Case #1 - The Crystal Shift 

The Raw Material Detectives are always traceable to probable cause. They have their thinking CAPAs on! 

Posted by Bruce Lehr April 25th 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.

FDA and Researchers Move Us Closer to New Clinical Model(s)

I read a couple of articles this evening that gave me hope.  We're starting to see some innovative thinking in how to conduct clinical trials that really make sense to me.  These new approaches to clinical trials seem long overdue and if adopted sooner rather than later makes me believe in a brighter future. 

First in a recent public meeting supporting the process toward renewal of the Prescription Drug User Fee Act (PDUFA), William Vaughn, health policy adviser at Consumers Union, told the agency it is past time when companies "must test new drugs against current therapies, not placebo".  In other words, we should begin testing drugs versus the current best in class to prove we have something better and not another "me-too".  That would be a step forward for patients I believe. See Pharma Times story.

Much more exciting (and more immediate), researcher at MD Andersen are conducting the Battle lung cancer study.  The study is looking a biomarkers from tumor biopsies of 255 patients in the study at defined short intervals during the study. The patient's disease is assessed to see if the drug regimen he/she is on is working or if the treatment needs to be changed.   This is a new adaptive trial design that is expected to enhance the chance of success of drugs in mid- to late- stage trials.  (See Fierce Biotech)

We all know about the number of drugs that have been failing to meet their clinical endpoints in phase II and III studies.  This type of design would better allow clinicians to match drugs to the patient or patient class that would be respond to a particular therapy.  It's another step closer to personalized medicine and could save drugs from failure by targetting them to the right set of patients. 

Couple this with an approach where you actually evaluate the treatement versus the best options out there - and hey - we might have something.

Posted by Bruce Lehr April 22nd 2010

Medicaid Discounts Drop Big Pharma Short Term Revenues

Several Big Pharma companies have revised revenue/earnings estimates for latter quarters in 2010 and the year 2011 as reported in the WSJ Health blog due to new requirements that the industry pay bigger rebates to Medicare.

Companies weighing in with reduced earnings estimates are:

Abbott indicated that it will cut its earnings estimate for 2010 by about $0.07 per share to $4.13 to $4.18. Revenues are estimated to be down by $230 M in 2010 and $200 in 2011.

Johnson & Johnson expects 2010 earnings to be reduced by a nickel per share and revenues to drop between $400 - $500 M.

Lilly cut its 2010 earnings estimate by $0.30 to $0.35 per share. It expects revenue to fall by $350 M to $400 M in 2010 and by $600 M to $700 M in 2011. 

According to analysts, not all companies will be affected alike.  It depends heavily on product mix.  BMS purportedly has the highest potential Medicaid bill with 10-15% of its revenues covered under the program. AstraZeneca looks a lot like Lilly.

Another unknown, rebate rates vary for managed Medicaid plans and fee-for-service plans.  So a Company's mix here too makes a difference. The price details of the two forms have not been spelled out yet under the reform bill.

Pfizer and Merck appear to be the lucky ones with lowest Medicaid exposure.  Maybe they can worry about patent cliffs instead.

Again, we're seeing significant changes in the enviroment that will only further spur the industry to changes its business and development models.  One can expect the industry to continue to shake-out and consolidate as pharma and biopharma coalesces.

Posted by Bruce Lehr April 22nd 2010

Whitepaper: Supplier-Integrated Raw Material Systems Support

My colleagues, Mason Williams, SAFC Market Segment Manager, and Brad Riesenberger, Corporate Communications have created a new whitepaper entitled, " Supplier-Integrated Support of Biopharmaceutical Raw Material Systems Promotes Operational Excellence and Risk Mitigation".

The paper discusses opportunities to reduce risk and cost by working with suppliers who can offer novel supply chain solutions and promote reproducibility in production processes. Vendor-partnered solutions are highlighted that can deliver leaner and safer processes for raw material handling.

Posted by Bruce Lehr April 22nd 2010

Evonik Moves Into China API Facility

Evonik has partnered with a European pharmaceutical company to open a new 70 m³ manufacturing facility to produce APIs.  The new facility, located in Nanning, China,  can quickly double its capacity if required. Evonik's collaboration partner has contracted for API services over the next several years.  The plant will produce cGMP compliant amino acids and amino-acid derivatives. It is part of the Health & Nutrition business unit.

"The new plant is an expression of our horizontal integration strategy," said Hans-Josef Ritzert, an Evonik Business Head. The term "horizontal integration" stands for a network of western (Europe, NAFTA) and Asian production sites from which Evonik offers customers tailored and exclusive solutions along the entire value chain of active pharmaceutical ingredients. "With this plant we will further consolidate our position as a high performing partner for exclusive synthesis," added Ritzert.

This is another example of a raw material supplier to the pharma industry relocating a manufacturing site to the East - and specifically to China.  This, despite, certain reservations among many Western pharma & biotech company Quality departments concerning the sourcing or raw materials in China due to well documented series of quality lapses - some with deadly consequences. 

However, I believe that while - right now - some Companies are gun-shy of Chinese source raw materials that this will necessarily be a passing situation. It is nearly inconceivable to me that Eastern countries like China, India, etc. could be excluded from the supply chain for any lengthy period into the future.  These are rapidly growing economies that will have too much global impact to be excluded.  That also becomes increasingly undesirable as Western manufacturers continue to install plants in this region - clearly you will want to source from these areas for these local plants if for no other reason. 

The Region is here to stay and we need to work to get raise the bar more rapidly in areas where the quality standards are currently lax.  As opposed to excluding these groups from the supply chain altogether. 

Posted by Bruce Lehr April 21st 2010.

 

Map of India Bulk Drug Manufacturing and Formulation Sites

This is a link to an article on in-Pharma Technologist.com that shows the location and density of India's pharma sites for bulk manufacturing and formulation.

  
The sites are marked clearly on maps you can access through the link.  You can refer to above map if you'd like to correlate sites better to India's states.

Posted by Bruce Lehr April 21st 2010.  

Pharmerging Markets Save the Day!

The pharmerging markets will drive growth in the world pharmaceutical market of 5-8% annually through the year 2014 according to IMS projections reported in Medical Marketing & Media.

IMS says this will happen despite the fact that drugs with sales of $142 B will come off patent during this time - removing an expected $80-100 B in sales from the market (about 2/3 coming out of US).  Six of 10 of the world's top selling drugs will face generic competition in the next 2 years.

How do we compensate? Pharmerging markets save the day!  IMS forecasts 14-17% growth in these markets representing an incremental $120 to $140 B in growth - during a period when Western markets piddle along at 3-6% growth.  This year IMS predicts 7% growth worldwide.

Posted by Bruce Lehr April 20th 2010.

Baxter is latest to Build Cytotoxics Manufacturing Capacity

The oncology market is projected to be one of the fastest growing segments in phamraceuticals.  New treatments for oncology increasing include the use of high-potent APIs and antibody-drug conjugates. 

Baxter BioPharma Solutions has announced (PBR) completion of its third expansion of its Halle, Germany manufacturing site. This course added 50% to its capacity for commercial cytotoxic manufacturing and also large scale lyophilization capability.   Their filling process uses cRABS(closed Restricted Access Barrier System) to enchance safety for operators and increase product sterility protection.

Baxter also added capability to do cytotoxic emulsions, liposomes and suspensions, along with a nanoparticle suite equipped with a high pressure homogenizer. The company feels it is now well positioned to support customer oncology projects from small scale development through commercial scale at one location.

If you have been paying attention, you will have notice a lot of market activity with regard to bringing on new capacity for the manufacture of high-potency cytotoxics and antibody drug conjugates.  SAFC has upgraded it facility in Madison, WI as well as opened new facilities in St. Louis and in Verona, WI.  Several companies in India have also brought on new capacity this year or begun new capacity construction.  Again, this speaks to the expected growth of the oncology space.

Posted by Bruce Lehr April 20th 2010.

Seattle Genetics Parlays ADC into CASH

As reported in today's GEN, Genetech will pay Seattle Genetics (SeaGen) a $9.5 M to renew licenses to specific targets using SeaGen's ADC technology.   Genentech has the right to use  the technology with antibodies against targets of its choosing. Genentech is responsible for discovery through commercilization activities.

SeaGen will receive licensing fees, milestone payments and royalties against net sales when the ADC products are commercialized.  Seagen believes the agreement further substantiates its industry leading position to enable the development of ADCs.  ADCs are increasingly important to new cancer therapies and are expected to address many unmet needs in the treatment of recalcitrant disease.

Seattle Genetics has realized more than $120 M through licensing of its ADC technology. ADCs are fueling a boom in new manufacturing facilities to make these highly cytotoxic drugs.  See the next post.

Posted by Bruce Lehr April 20th 2010.

Amylin Counting on Swift Bydureon Approval

I feel compelled to update Bydureon progress since I've posted about it a few times.  I don't feel that I can leave you hanging in suspense. 

The WSJ reports today that Amylin will send its response to the FDA this week on the agencies queries regarding Bydureon.  Bydureon is Amylin's important new 1x per week drug for the treatment of type II diabetes.

The drug's success is critical to Amylin's future financial picture.  When it is approved, Amylin's partner, Eli Lilly, will bestow a $40 M milestone payment on the company. The drug is also needed to fight off new competition from Novo on Amylin's current product, Byetta.  Lilly is submitting Bydureon for approval in EU.

The FDA in March had asked for more information on Bydureon's label, risk management plan, and manufacturing process.  No new clinical data was required.  The review period that the FDA will take is unknown but can be within 60 days to 6 months depending how the resubmission is treated.

Bydureon is a new class of compound called a GLP-1 analog that is similar to a human gut hormone that induces greater insulin production to regulate blood sugar levels. Once Bydureon is approved, Amylin plans to continue work on a next version drug that can be administered only 1x per month.  This is in preparation for expected competition from Roche's Taspoglutide and GSK's Syncria both in late stage trials.

Amylin expects to be showing positive operating cash flow by the end of 2010 based on Bydureon approval.   Start the countdown now.

 
Posted by Bruce Lehr April 19th 2010.

Dr. StrangePost - Or How I Learned to Love the Blog....................

For those few of you (and you're very erudite I'm sure) who have actually read a substantial majority of my posts on this blog, you may ask yourself what's the process of selecting topics.  It doesn't seem like there is a theme going here.  As many blogging books advise, write about something you know and the narrower the better to build a community following.  Seems like good advice.  I tried that but ran out of subject matter quickly.

As a result, after making probably a dozen posts on raw material characterization (see Jan 1st, 5th, and 10th to get ball rolling) topics, I found I was going to be out of fodder until the next phase of this program was completed and data starting coming in (soon, soon). 

That left me with a decision.  Should I blog less frequently and wait for the data?  I was worried about losing writing momentum, plus I had never blogged so I felt that I needed to learn some things (etiquette, software, etc.) and test others (written content, pictures/video, voice).  I opted to endeavor to persevere.

So I decided to post on other topic areas within my business & the industry.  By forcing myself to read (first) and then write daily, I really help myself stay abreast of industry topics and trends.  What I post -- usually relates to me in the following manner:  industry trend (R&D restructuring), competitors to my business, big customer for me or one that I wish was a bigger customer for me, science directly related to products/services that I sell, emerging geographic markets - mainly BRIC, and legal decisions that I feel will have a significant impact on the market environment and competitive landscape.

Given my employer, this opens up quite a spectrum of competitors, technologies, markets, products and services (these alone encompass raw materials for use in biopharm/pharm production, CMO services like vaccine manufacturing and manufacture of ADCs, analytical services, cell engineering, etc).  Thus, the smorgasbord feel - perhaps - to my postings.  By following this path, there is almost always something newsworthy related to the topics above.  

So I've been doing this 3.5 months, so what might I observe? 

Clearly the industry has reached a stage of maturity where restructuring is necessary.  We're effectively seeing a coalescense of the pharma and biotechnology industry.  This means that many biotechs will go away or be absorbed into larger companies. It means the pharma guys will bring techniques like lean (to take out cost) and better risk management practices to biotech groups.  It is needed to compete as the generics and biosimilars emerge as strong competition during this period.  It means companies will reduce their internal R&D - we've all seen the layoffs.  It means new R&D outsourcing models - with both private and public sectors and parnerships - even amongst peers see Asia Cancer Research Group.  It means companies need to come up with a strategy to address emergine markets and to compete with generics/biosimilars. If you can't beat 'em join 'em - companies like Sanofi-Aventis, AZ, Pfizer and Cephalon all have made moves on generic producers.  On the flip side, Teva has made moves in the oncology area for more novel compounds to diversify is world leading generics portfolio.

Markets are moving East (doh!).  You could knock me over with a sledge hammer, pile-driver and Sherman tank!  Hopefully, we've all heard of the BRIC countries - China and India in particular are especially prominent in the pharma arena.  They represent triple threat - customers, service providers and competitors!

With regard to competitors, I note the emergence of CRAMs in India and China - particularly the former - and the pharma companies in India who are opening CRAM divisions too.  From a company  perspective - I notice that Lonza has continued to shift resources East and has opened facilities for both small and large molecules in India, China and Singapore.  Again this is all consistent with the market data that the East is growing much more rapidly than the developed countries in the West and represent best targets for incremental sales growth. Also it is difficult to ignore when a new competitor like Merck KGaA enters the supplier space in a more agressive way through its acquisition of Millipore. Clearly, Merck is serious about further diversifying from its drug business and is trying to build a portfolio of strength with its chemicals and the filters/reagents that the Millipore portfolio will add - all the better to service a bigger chunk of the biopharm production flow.  And remember, Merck's CEO remains adamant that this acquisition was worth every single penny.

Otherwise, from a technology point of view, I plan to spend more time writing about the zinc finger nuclease technology exclusively licensed by SAFC, and its use to create very novel platform production CHO cell lines (or other cell types) for use in the biopharm industry.  This will enable more control over the efficacy of a drug (e.g. MAbs glycosylation) and may pay particular dividends in the manufacture of non-MAb proteins. 

I also plan to follow closely any impact the Judge Sweet gene patent ruling will have on the evolution of the industry - both legal and development climate.  I imagine the latter will take a few years to be fully evident as we wait for further appeals and perhaps other cases to hit the courts.

And, believe it or not, I expect to start a new series of posts based on raw material characterization - entitled "The Raw Material Detectives".

Posted by Bruce Lehr April 19th 2010.

 

New Feature - "The Raw Material Detectives" Series

Coming soon to a Big Red Biotech Blog near you! 

I will soon begin a new series called "The Raw Material Detectives" that will describe unusual cases of raw material misbehavior and how the Raw Material Detectives (our heroes) investigated and resolved the issues.  This will hopefully reinforce the need to have good raw material characterization and traceability on products that you are using in the manufacture of your biological drugs.

Now let's give it up for Elvis Costello and the Attractions singing "Watching the Detectives"

Posted by Bruce Lehr April 18th 2010.

When are The Price's Right for Dendreon's Provenge?

The analysts have lined up and placed their bets.  The early over/under for the predicted pricing of a year's course of Provenge per patient is approximately $61,700 according to Luke Timmerman's poll of 7 industry analysts - the folks who should know - even though they're guessing like you and me (maybe a bit more knowledgably than you or me).

Price estimates range from $40 K to $75 K with other analysts not included in this calculation even projecting over $100 K pricing. Not too worry though, this isn't too big a decision for Dendreon - they only have to recoup a $783 M deficit generated since 1992.  Nothing at stake here if they set the price too high for any 3rd party payers to foot the bill. 

And you thought pricing was easy?  

Posted by Bruce Lehr April 16th 2010

UPDATE FROM FIERCE BIOTECH - FULL COURSE OF TREATMENT TO COST $93 K.

More Oncology News as Teva Licenses from Mersana

Teva reached a licensing agreement this week with Mersana Therapeutics for the development of its XMT-1107 molecule (a novel anti-angiogenic fumagillin analog conjugated to Mersana's Fleximer). See full report at Seeking Alpha. The deal helps Teva diversify from its generic portfolio. Like most deals these days, Mersana will be compensated up to $334 M based on achievments of milestones, and is also eliglible for royalites.

Mersana will begin phase I work with XMT-1107 next quarter. Teva continues its move to oncology with this second licensing deal in the past few months, and cut another deal for OncoGenex's late stage OGX-011 (custirsen sodium) this past December. This drug is aimed at treatment of prostate, non-small cell lung cancer, and breast cancer. Clearly Teva is attempting to capitalize on the potentially lucrative growth predicted with cancer therapeutics - and to diversify from its lower margin generics.

Posted by Bruce Lehr April 16th 2010.

Starving Cancer Brings Home Bacon for Agios Pharma

Xconomy reports that Celgene has cut a deal with Agios Pharmaceuticals that will make the latter as much as $130 M richer. This in exchange for rights to Agios experimental technology to starve cancer cells.

The deal is for roughly $10 M in cash and equity investments up front with the possibility of $120 M in milestone payments and even comes with an option to extend.

This is an example of a company with a new idea - killing cancer cellls by blocking metabolic enzymes.  Agios has been able to show proof of concept in a study published in Nature demonstrating the starving effect on brain cancer cells.

Agios also had the foresight to bring on Genentech veteran, David Schenken, former head of cancer drug development, as its CEO.  No doubt further adding to its credibility with Celgene.

“This transformational alliance provides Agios with the long-term resources and flexibility to extend our leadership position in the cancer metabolism field and to advance our capabilities and programs as an integrated, independent company,” Schenkein said in a statement.

Agios has now raised over $163 M in less than 2 years to fund its cancer metabolism treatments - and that's a lot of bacon in this economy.

Posted by Bruce Lehr April 16th 2010.

Multi-gene and/or partial/full sequencing in Cancer Dx

Think how the gene patent issue might play out in the scientific, business and legal worlds if the aims of the International Cancer Genome Consortium (ICGC) reach fruition in the development of a number of new cancer diagnostic tests and therapies?  How might ownership quarrels around individual genes impede progress with tests based on multi-gene or partial/full genome sequencing?  Think about that as you read this update on ICGC progress.

 The ICGC consists of leading cancer researchers (> 200) from all over the world.  Since 2008, the group has been working to sequence the 50 most common types of cancer, generating 500 sequences for each type from 25,000 different patients.  The plan is to make these sequences freely available on the internet to aid cancer researchers across the globe.

As reported in The Medical News, datasets of breast, liver and pancreatic cancers have already been posted to the ICGC website.  Sir Paul Nurse, 2001 Nobel Laureate, states that "the plans for data release will facilitate efficient deployment of resourcesand ensure that all cancer researchers can use the data in a timely manner"  - i.e. this is a so-called open source collaboration.  Professor Eric Lander, President and director of the Broad Institute at Harvard and MIT, further states "We are moving into an era where the prescription for cancer treatment should be based on the genetics of each patients tumor."

Ed note: I would submit that doesn't sound too compatible with the idea of companies or academic institutions owning individual gene sequences. The tests coming out of this project might be really Sweet.

Gene sequencing technology has progressed to the point where is will likely be feasible to do partial or even full sequencing of a cancer patient's tumor for approximately $1000.  Factoid: The original human genome project sequenced half a dozen individuals at a cost of $1.5-2 B and took 15 yrs.  We can now do that in 1 week at a small fraction of the cost.

A paper describing the ICGC study will appear in today's publication of Nature, and individual study teams will be presenting their progress at the AACR meeting in Washington, DC next week (April 17th-21st).

Posted by Bruce Lehr April 15th 2010.