Chapter Ten

The Pharmacy of the Future

While personalized medicine has clear medical benefits, the concept of deliberately narrowing the target markets of drugs in development creates a dilemma for pharmaceutical developers.

The traditional pharmaceutical companies will need to rely more on innovation as revenue models fueled by a few billion-dollar blockbuster drugs are no longer relevant. Eventually, all companies will need to rely on a broader array of smaller market drugs to fill their product portfolios. Instead of economy of manufacturing for a single drug, companies will need to develop broader economic models involving many individual oligomers – or conventional small molecule drugs. In addition, companies focused on rare and lethal diseases will have to balance the cost of the development of each of their new personalized drugs with the much smaller, more focused target audience.

Should the individual patients or their healthcare insurance bear the cost of these new therapies? I anticipate that some of the new oligomers will cost $250,000/year or even more. Or should the cost of these drugs for a few be spread across society as a whole? Whoever pays, it should be noted that their cost may be considerably less than the cost of not having adequate, safe treatment. That cost is currently born by the patients, their family, their healthcare insurance systems, and by society. The cost of caring for a patient slowly dying from a lethal genetic disorder may far exceed the cost of a new treatment – in terms of both healthcare dollars and impact on the patient’s family, community, and the economy.

Speed to market will be even more important than today where millions of dollars may be lost if a new drug is delayed by a few weeks from being approved. In the future, delay in a drug gaining approval will not only affect the company coffers, but in the case of rare disease treatments, it may cost patients their lives.

The regulatory agencies are aware of the dilemma they face. They are keen not to delay a lifesaving medicine from reaching the market. At the same time, though, they must be sufficiently confident that the benefits of the drug outweigh the risk. Has the sponsor presented enough data to allow that informed decision to be made?

That is one good reason for the companies developing drugs for rare diseases, to be in frequent and detailed dialogue with the FDA. Unfortunately, the FDA, as with many important regulatory agencies, has suffered cutbacks and layoffs, while the workload has become heavier and more complex for the remaining staff. In addition, if the agency is too approachable there will be a fear of collusion with the drug companies and critical voices will be raised by agency watchers.

A more flexible regulatory authority review is already enshrined in the orphan drug regulations, and oligomers in development for rare diseases will benefit from that. In addition, it is likely that far more extensive, sophisticated and longer term monitoring will be required of the new drugs after they are approved. That trend is already in evidence for new medicines. Nobody wants to see another Vioxx or

Avandia debacle, so more extensive post-marketing safety surveillance will become the rule rather than the exception.

The oligomer (or oligonucleotide, the terms are generally used interchangeably) community is optimistic about the future of these gene patches and desires transparency so that doctors, healthcare scientists, and consumers alike can become better informed and share the excitement.

Over the last few years, new societies have formed, like the Oligonucleotide Therapeutic Society, OTS, where scientists exchange latest information about the development of these patches. As these societies grow and the pace of progress speeds up, distilling the information overload down to manageable chunks for us all to consume will become a mighty task. Books, journals, television, and the Internet will all be harnessed in providing doctors, and you, with updates and advice.

In the future, not only will your doctors and their offices change to encompass the rapidly increasing amount of genetic data, but the drugs they prescribe as well as your hospital dispensaries and your local pharmacies, will change too. The regional warehouses and distribution networks that supply these pharmacies will also have to rapidly adapt to the new paradigm.

Pharmacies now stock a surprisingly small number of drugs – only about 30,000 discrete medicines, although many are made by multiple different manufacturers and in different strengths, bottle size, or formulations for different routes of administration. The medicines are often relatively inexpensive due to the tremendous technical advances in quality manufacturing. The original manufacturer of the first brand of a new drug can charge a premium price to recoup the enormous costs of development. The cost of manufacture of conventional medicines, especially pills, is modest in comparison to the new gene patches, which require many additional steps, some of which are quite complex, in their manufacture.

So today, pharmacy shelves are stocked with bottles and packets of pills which have been relatively inexpensive to manufacture. Pharmacies can afford to buy large quantities of them, each with long shelf lives. The pharmacy, retailer, distributor, and manufacturer can all benefit from bulk production, packing, purchasing, and shipping. Each pharmacy may have hundreds, even thousands, of patients on each drug, so they turn over their massive stock on a regular basis. Inventory control is vital to ensure they stock enough of the popular drugs to meet demand and not too much of the less popular medicines since shelf space is valuable.

The new oligomers will require development of a leaner and more efficient supply chain. The initial cost of manufacture will be significantly greater than today’s blockbuster pills. As more manufacturers develop the capability and experience, and the raw materials – the chemical building blocks – become more plentiful, so the price of manufacture will fall. However, instead of each pharmacy having hundreds or thousands of patients on each of their drugs, each oligomer may only be appropriate for a very few highly select patients with the exact genetic mutation for which the oligomer has been designed. For some rare diseases, there may only be a handful of patients across the whole of the United States. Thus it would be totally impractical for every pharmacy to stock that oligomer.

Actually, these oligomers are unlikely initially to be dispensed by your neighborhood retail pharmacy at all. For some years after the first few oligomers have been approved, and others accelerate through development, these new gene patches are likely to be available only to select doctors. Perhaps they will work in special teams or hospitals with the skill to assess and monitor the disease being tackled and prevented. The pharmacies of these hospitals are where the new oligomers will be delivered. The shipments will be quite small, so the supply and distribution will need to be more highly coordinated.

Some of the new oligomers may only be administered to handfuls of patients worldwide. So instead of the current system where manufacturing can occur in numerous countries around the globe, the new gene patches may only be made in one factory. Shipping overseas, meeting export and import requirements, and then getting from the port of entry in the destination country to any distant hospital will require considerably more sophisticated tracking and logistic support. There may be, for instance, more security than is currently the norm.

Gradually, a few hospitals will stock a small number of these new oligomers as vials of injectable product, or freeze dried powder for reconstitution at the time of administration. The first candidates for possible treatment with these gene patches will reflect the interest and expertise of the doctors at the institution. It may be the only hospital in that country, continent, or even the world dealing with that particular rare disease.

In time, many large hospital pharmacies will carry a large array of gene patch medicines. Each oligomer, though, will be for a small, select group of patients, with a variety of rare diseases or a unique genetic pattern for a more common disease. Perhaps the stock will be released to each hospital or clinic on a named patient basis, with responsibility for monitoring the products’ longer term safety shared between the hospital-based doctor, the hospital pharmacy and the manufacturing company.

Initially, the new gene patches will be administered by the named hospital physician who cares for the disease in question. Only as experience is gained with these oligomers and their safety record becomes established over years will your primary care doctor be able to administer them. Even then the initial prescription may be made by a super specialist who will share the safety monitoring with your local doctor.

The vials of oligomers may start off at the regional center and then transfer on a named patient basis, to a local hospital or to your local doctor to administer them.

Imagine a world where oligomers are developed for just ten percent of the one in ten Americans with a rare disease, or one out of every one hundred patients. If your doctor has a list of three thousand patients, that means thirty patients (3000 divided by 100) will be receiving an oligomer once a month. If those who suffer from rare diseases return to the super specialist hospital every six months for shared care, your neighborhood doctor may need to store 180 vials of oligomers to cover the period between visits to the specialty center. That is certainly manageable in most offices and clinics.

Patient advocacy organizations may be able to help with the identification of patients. They may also have lists of the small number of hospitals where each new oligomer will be available. Thus they may play an even more important role in future, linking patient to hospital, and accelerating access to these new medicines.

In this possible future, the hospital where the super regional specialist works will be the site where the diagnosis, assessment, and initial treatment of a new patient with a suspected rare disease will take place. Once the disease has been stabilized, the patient will be referred to a neighborhood local hospital or doctor’s office where the drug can be administered. Since many genetic diseases will be diagnosed at birth from the samples taken from a new baby, newborns will be referred to the regional hospital and this is where the new treatment will be explained to anxious parents. The baby will have no signs of the disease in question. Everyone’s aim will be for that to remain the case.

Electronic medical records and bar coding of new drugs will become the norm. They will link the right patient to the right drug at the right dose, administered at the right time. It will automatically be confirmed as the drug is dispensed. As a baby grows and gains weight, the dose of a new oligomer will need to be adjusted and the cumulative dose of drug tracked. A new batch of stock will be ordered as existing stock is utilized, in good time for the next administration. Or a set of vials will be produced, sent to, and stored at the specialty hospital to be subsequently sent back to the local team. Much of that supply-tracking technology is in place now for existing drugs.

Summary

When you put all this information together, you get a clear picture of what medical practice will look like in the future, in terms of dispensing patches for your genes:

If your hospital specialist prescribes an oligomer, the hospital pharmacy will perform a verification check of your electronic medical record to confirm the oligomer you need, and the dose. The vials of freeze dried oligomers will be stored in the pharmacy or in the future may be transferred to your local doctor’s office to be kept in a secure cabinet. Freeze dried product will have a much longer shelf life at varying temperatures and will therefore be far easier to store than already dissolved product, even in the same glass vials. As the vial is removed from the secure cabinet, it will trigger an automatic request to the manufacturer to start producing a new batch, like the system used in hotel minibars. Sterile saline will be injected into the vial and the oligomer will be reconstituted into solution. The vial will be bar coded, so it can be checked against your record to confirm that it is the right medicine for you. In fact, bar coding a vial of your personalized oligomer will allow it to be tracked from manufacturer, to distributor, to warehouse, to airport or trucking depot, to the hospital and onward to your doctor. All of these locations will have bar code reading equipment so that the vial of your oligomer can be tracked across time and space, much as a FedEx package is today.

Before your doctor administers your monthly dose, she will check that you have not reacted adversely to previous injections. Any adverse events you report may be transmitted back to the manufacturer, with that safety information being sent on to the FDA’s safety reporting system. While each manufacturer will maintain a database about the safety of their oligomer, or oligomers, the FDA will keep anonymous detailed versions of all safety reports from all manufacturers and thus have a far more complete picture of the overall safety of the numerous types of gene patches already marketed or in development.

With the prescription of these new personalized gene patches comes a much greater chance of ensuring benefit and preventing harm. But the patches will be made on an almost individual basis and they will need to be shipped from manufacturer to the patient’s hospital pharmacy directly by a far more sophisticated system than that employed today. From there, the oligomers may be transferred to a named doctor, close to the patient, who will share care with the instigating hospital specialist.