The Soul of Biotech

This post originally appeared as a guest post on the Xconomy news site.

Good morning from Mountain View, CA, and from the close of the 2012 Personalized Medicine World Conference, which brought together thought leaders of business, government, healthcare-delivery, research and technology. Four themes that emerged from this year’s program:

• Greater optimism, triggered by the 2011 approvals of two major oncologic agents paired with companion diagnostics: vemurafenib (Daiichi Sankyo and Roche / Genentech) for patients with metastatic melanoma with a mutant biological pathway known as BRAF V600E and crizotinib (Pfizer) for patients with non-small-cell lung cancer that overexpresses a protein called ALK. Walter Koch from Roche and Hakan Sakul from Pfizer proudly discussed their development processes and speedy approval timelines. Those approvals were also cited by several other talks as examples of major progress made in the quest to deliver the right drug to the right patient.
• Greater clarity from the FDA. Although the FDA was not able to meet its self-imposed deadline of year-end 2011 to finalize guidance to industry on the best practices for developing companion diagnostics, Elizabeth Mansfield reiterated Commissioner Hamburg’s commitment to personalized medicine and told the audience to expect final guidance before the end of June. Mansfield also said that the FDA would provide guidance on how to co-develop a drug & test in parallel, as well as how to “enrich” clinical trials through careful selection of patients, based on their genetics. Both of these important regulatory steps could happen in 2012. The most surprising revelation, though, was Mansfield’s staffing: her group has just four people to evaluate all personalized-medicine-related medical devices.
• More sequencing. Just a few weeks ago at the JP Morgan Healthcare Conference, 800-lb sequencing gorillas Illumina and Life Technologies / Ion Torrent announced that scientists can expect the $1,000 genome by the end of 2012. Piggybacking on that announcement, Mostafa Ronaghi, chief technology officer of Illumina, presented a thorough overview of his company’s progress to date, bragging that 90 percent of all sequences produced worldwide had been produced on an Illumina instrument. Among other projects, Ronaghi’s team is working on techniques to accurately cover the 8 percent of the genome that cannot be sequenced because of repetitive regions. (Ronaghi made his presentation just hours before news broke of Roche’s unsolicited $5.7 billion takeover bid for Illumina.)
• More translational bioinformatics. Given the implied data glut that whole genome sequencing will produce, last week’s conference revealed more accomplishments in the application of bioinformatics to the remedy of disease. One of the unsung heroes of this year’s conference was Elizabeth Worthey from the Medical College of Wisconsin, who walked the audience through a case study of a pediatric patient presenting with undefined inflammatory bowel disorder. Worthey’s whole exome sequencing and variant analysis of the patient revealed a key mutation in the XIAP gene. A cord blood transplant ultimately cured the child, who was eating, drinking and playing again within four months.

The Promise and the Peril of Personalized Medicine from Jeriaska on Vimeo.

Many thanks to Drew Reynolds for taping this and editing together this abbreviated version. The uncut talk was about ten minutes long — I started out explaining what treatment-response biomarkers are, and how they can improve patient outcomes and save money for payors.

The EEOC has invited the public to comment on the Genetic Information Nondiscrimination Act (GINA). GINA was passed in the spring of 2008 as a way to bar employers from discriminating against employees on the basis of genetic information. GINA also prevents healthcare insurers from discriminating based on genetic information.

GINA is an important step forward, as mentioned by Wayne Rosenkrans at the HBS Healthcare Conference. There are two obvious deficiencies in the current law:

1. There are no restrictions on life insurance companies. A life insurance company could still deny coverage (or even revoke coverage) if it learned of your genetic predisposition to a certain disease state.

2. There are no restrictions on the genetic research activities of personal genomics companies such as 23andMe and Navigenics. Privacy and security regulations are still up to the individual company and the license agreement it enters into with its customers.

Here’s to hoping that activists will take the opportunity to help shape GINA into a law that will cement the foundation of the ethical use of genetic data for the new millennium.

The next session I attended was the personalized medicine panel, which was new this year. The panelists spoke to a standing-room-only crowd in an HBS lecture hall. The panelists briefly explained what personalized medicine was, and emphasized its importance as technology began to deliver whole genome sequences for less and less money. The first human genome cost about $3 billion dollars to sequence. As of March 2008, that price had dropped to $60,000. More recently, SingularityHub predicted that whole genome sequencing would fall to $1,000 before the end of 2009.

So what are some of the consequences of a high volume of genetic data becoming rapidly available?

• Noubar Afeyan provided an overview of the current diagnostics market. One company recently did a deal with Humana to develop simple treatment response markers (non-predictive) — the kicker is that patient co-pays will depend on the values of the treatment response marker.

• Dr. Teresa DeLuca, Medco’s VP of Personalized Medicine, capably explained not only how personalized medicine can achieve improved outcomes in targeted patient populations, but also how the technology can reduce costs for payors. Payors may not be able to make a patient go into wellness program or enforce a patient’s compliance, but they will soon be more able to get the right patient the right drug at the right dose at the right time. Medco is working to create diagnostics reports for doctors that provide medication recommendations for patients.
• Mara Aspinall, president of Genzyme Genetics, emphasized the need to more deeply understand the pathways and MOA for the drugs we already have, and add the right diagnostics and pharmacoeconomic data to deliver a total value package for payors.

Curiously, Afeyan also mentioned current research into biomarkers that may predict response to anti-TNF medications such as Enbrel.

Later on, I also spoke with Wayne Rosenkrans, the panel moderator and the chairman of the Personalized Medicine Coalition, which works on evolving healthcare policy in this area. He agreed that the Genetic Information Nondiscrimination Act was a promising step forward, but insufficient protection for most patients. Case law will have to fill in the gaps left by the law, which is only months old.

Danny Halperin is a second-year graduate student in Molecular & Cellular Pathology at the University of California at Los Angeles, working in the laboratory of Dr. Peter Tontonoz. Before attending UCLA, Danny spent four years at Amgen in Clinical Immunology supporting pre-clinical and clinical development of biologics. Danny and I sat down over Thai food in Santa Monica on Thursday evening to talk through the relationship between academic and industry research, the promise of pharmacogenomics, and building a healthy R&D culture. This is the first in a series of interviews.

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My friend Lexi sent me a link to a NYT article that discusses personalized medicine (also known as pharmacogenomics), which is an area of great interest to me. It’s what I focused on in my master’s work, and it’s an area that, given the right opportunity, I intend to start a biotech in one day.

The article describes the promise of personalized medicine reasonably well: The opportunity to select the best therapy for a patient based on his or her genetic profile. Dr. Friedman correctly notes the opportunity for improvements in patient outcomes in terms of drug efficacy and safety, with a special eye towards his own specialty of psychology. He goes astray, however, at the very end:

Aside from the potential to transform clinical psychiatric practice, these new developments will surely change the relationship between doctors and the drug industry and between the industry and the public. Direct-to-consumer advertising will become nearly irrelevant because the drugs will no longer be interchangeable, but will be prescribed based on an individual’s biological profile. Likewise, doctors will have little reason to meet with drug company representatives because they won’t be able to give doctors the single most important piece of information: which drug for which patient. For that doctors will need a genetic test, not a salesman.

I find several things wrong with this paragraph.

Although doctors may find it challenging to select the right treatment for a condition (especially depression!), the available therapies are hardly interchangeable, even today. That’s one of the most important reasons why clinical trials exist: to demonstrate clinical attributes that differentiate a given drug from other existing therapies. Also, Dr. Friedman assumes that the genetic screens will always produce extremely clear results — but what if they don’t? Or what if the screens can only point to a set of therapies — what then? Those are critical situations in which reps will be able to consult physicians on the remaining differentiating attributes.

Furthermore, reimbursement education (for both the genetic screen and for the drug itself) is also a major function of most reps. Many doctors and caregivers struggle to understand whether or not a patient can afford a therapy, especially if the patient is on Medicare. Drug companies, including Amgen and many others, often step up to help educate physicians and guide patients to the form of coverage that best allows the physician to treat in the manner they see fit. That role will become even more critical with a screen to pay for on top of the therapy.

Finally, I don’t see personalized medicine making direct-to-consumer advertising irrelevant. If anything, marketers would focus even more on getting patients into the office to get the test, thus feeding the genetic screen funnel.

What about you? What do you think genetic screening will mean for the pharmaceutical and biotech industries?