An occasional story regarding my perspective on some of the drugs I was associated with in my career.

A loud chord sounded across the general session ballroom and the lights dimmed as the spotlights lit center stage. A lovely young woman in her 20s walked out, looked for her mark on the floor, hit it, and appeared to hesitate. She finally managed a muted “Hi”, and most of the 600 people in the audience responded in unison with a “Hi!” right back. Her delight, and the light laughter around the room, seemed to calm her as she found the teleprompter and began her story. It was a story about how the disease of epilepsy, and the medicines used to treat it, had impacted her life. She related how she began having seizures as a small child, which kept her from going to nursery school, kindergarten, and neighborhood playgroups. Her seizures were not well controlled during elementary school years, so she was home-schooled and made few friends. She and her parents bounced from neurologist to neurologist looking for answers. Eventually, the medicine cocktail she was taking blunted most seizures and she was able to begin public middle school. Unfortunately, the side effects from the medications were negatively impacting her schoolwork and she had to return to proctored homeschooling, all the way through high school.

Toward the end of high school, a new neurologist revamped her therapy and added a drug called Lamictal and, through a combination of medicines, she finally achieved seizure freedom. Side effects were under control and, miracle of miracles, she began college at NC State University. She stood there on stage beaming as she told us that she graduated in 4 years and was now engaged to be married to a guy she met in class.

As the applause died down, Dave B., one of the best marketers I’ve known, came out on stage to thank Sarah for sharing her story. Then he said, “Sarah, sitting in the audience are all the Salespeople at GSK whose job it is to bring the news of Lamictal to doctors across the country. Is there anything you’d like to say to them?”

Well, we all expected her to give genuine thanks for what we do every day. Instead, she slowly turned to the audience and just said 2 words…Try Harder.

She went on to say that it took much too long for her and her parents to find a physician who had the same expectations of therapy that they had. It took much too long to find a physician who had a full understanding of therapeutic options available, and the expertise to navigate their risks and benefits. She said, quite simply, that it took much too long for Lamictal to become part of her life.

And that’s pretty much the reaction of most epilepsy patients who’ve found Lamictal (lamotrigine); a true wonder drug.

Epilepsy is a scary disease. For everybody; those experiencing the seizures of course, but also for those who watch helplessly and don’t know what to do, and the caregivers who are often confounded by the disease. Seizures are caused by unchecked electrical activity in the brain, and they are hard to treat. Most treatments focus on reducing electrical connections in the brain to blunt any storms. Unfortunately, tamping down the brain, well, tamps down the brain! Cognitive function suffers; presence, personality and drive are all impacted. And the other side effects of most drugs used to treat epilepsy are tough. Besides the obvious and important impact on cognitive function, many cause a hit to self-image with such things as weight gain, bleeding gums and hair loss. Others may cause more serious problems like retroperitoneal fibrosis (scarring of the abdominal cavity). One shockingly common drug inhibits folic acid, which is critical for the formation of an intact nervous system in babies, so is a risk for women of child-bearing age.

Lamictal works in a unique and different way and offers dramatic efficacy. Its first indication was for Lennox-Gestaut syndrome, which is a severe, difficult-to-treat, (mostly) childhood constellation of many types of seizures. Patients usually wear helmets. Lamictal picked up indications for many other types of seizures during its marketed life. In fact, it was at a launch meeting for a broader range of seizures that Sarah addressed the NeuroHealth Division of GSK.

Besides dramatic efficacy, a critical benefit of Lamictal is that it does not meaningfully interfere with normal brain activity. Hence, little effect on cognitive ability. This is a huge deal but it’s important to point out that a clinical program to prove this would be daunting. So GSK could not, and did not, promote this benefit. But any practitioner with even a little experience with Lamictal could certainly see it.

Alas, every silver bullet has its issues. For Lamictal it is that in fewer than 1% of patients it can cause a severe reaction which may include a rare rash known as Stephens-Johnson syndrome. This is a serious and painful disorder of the skin and mucous membranes which can, although rare, end in death. As a result, a “Black-box” warning accompanies the drug. This is the highest safety-related warning that a medicine can carry, and it is printed with a black-ink ‘box’ or border around the text in the Product Information.

To mitigate this effect, Lamictal must be started slowly with very low doses that are gradually increased over time to achieve a therapeutic dose. And the dosing needs to be adjusted based on weight, especially for children, common epilepsy patients. That’s not all. Lamictal interacts with other drugs commonly used in epilepsy. Well, more correctly, THEY interact with Lamictal. Some drugs reduce the bioavailability of Lamictal by half, while others actually double it. As you can see, the dosing for Lamictal is anything but straightforward, and although GSK built brilliant dosing kits for starting adult patients under different scenarios, many physicians just did not want to work so hard to write a drug, especially for kids. Many used the Stephens-Johnson rash warning as their reason for not using it.

While that may sound sensible, the truth is that over 400 drugs carry a Black-boxed warning in the US, including some very common ones: Antidepressants like Prozac, Zoloft, and Celexa; bronchodilators like Advair and Symbicort; antipsychotics like Seroquel; antibiotics like Levaquin; and many pain killers. When one considers the poor efficacy of most older drugs used to treat epilepsy, and the high side effect impact, a little work to get Lamictal on board, as in Sarah’s case, is usually worthwhile.

To make matters worse though, Lamictal also faced significant marketplace headwinds. A year before Lamictal was launched, another promising drug for epilepsy hit the market: Felbamate. It was quite efficacious, promoted aggressively, and physicians readily adopted it. Unfortunately, very serious side effects were soon reported that did not show up in early clinical trials. In short order the FDA restricted the drug and the manufacturer withdrew it from the market within one year of launch.

Lamictal was about to enter this sensitive, cynical environment. Fortunately, several resourceful people in the Lamictal marketing department had the foresight to understand what was needed.

Epilepsy is a multi-pronged, non-specific, complicated disease state and it’s treated by the sophisticated and demanding specialty of Neurology. And the treatment programs for epilepsy are broad and intricate. Lamictal itself is a complex drug with many considerations. A traditional GSK Sales Rep, with 3-4 products in their bag, and a focus on General Practitioners, would not give Lamictal a fair chance. The marketing team, led by Kevin R. proposed the development of a new Specialty sales force to promote Lamictal to neurologists and epileptologists only. The US President of Glaxo, actually Glaxo Wellcome at the time, Chris Viehbacher, wisely approved the budget to develop the new division. It was a small force, maybe 100 Reps who, truth be told, based on their background and education, were no different from the general line Reps. BUT, they sold Lamictal exclusively and trained hard on all things epilepsy. After 3-4 years they became a formidable force, eventually going toe to toe with everyone from Child Neurologists to Chiefs of Neurology at teaching institutions.

It was at this point that I got a call from an old friend and Regional Director named David from Wisconsin. David is an amazing guy. He is brilliant, always has an opinion, and is never shy about sharing it. But he rarely couches it in a way that is protective of the recipient of his wisdom. I love that about him. You get the unvarnished truth from David. And he is absolutely right a frightful amount of the time. Also, his people love him because they learn something every day, and it is clear that his one goal is to make them more successful. Anyway, I get a call from David encouraging me to apply for a NeuroHealth Director position that has just opened in Indiana/Michigan due to expansion. He figures I’d be perfect for it. Maybe, but I wasn’t so enthusiastic about essentially a lateral move. I had a great District that I cared for, was doing well, and had a great boss in Lou Esgro. But he sold me hard on Lamictal itself, the high level of discussions going on in the office and hospital, and the impact any one person could have in a small team like NH. He sold me on the leadership team and a looming merger with another specialty team. NH was headed at the time by a woman named Diane T. who really drove its growth and development. She is brilliant, a natural marketer, and a great strategist. If she has a weakness, it’s in the softer skills. She was an intimidating person, but I always got a kick out of her because she obviously had a Development Plan that emphasized demonstrating empathy and relating to others. Her attempts were laudable but transparent. At her right hand was Dawn B., another exceptionally capable person adept at implementation. Finally, NH came under the auspices of General Manager and non-traditional leader Steve S. He was an idea guy who sometimes wore black T-shirts to work/meetings and occasionally sported an earring. He climbed the corporate ladder in the Managed Care division of the Company. Steve had soft skills in spades. Quick Story:

One day Jeff, a Medical Information Scientist (MIS) for Glaxo, visited Steve in his office to say good-bye. MIS respond to health care practitioner’s questions about our products, and often help out at Sales Training. This guy was the first MIS for Zantac, the product that put Glaxo on the map, and he deserves some credit for its success. We all knew who he was, and Steve got to know him many years prior when he was a Manager in the Sales Training Department. Turns out Jeff was being laid off during one of the downsizings. Steve learned that Jeff was only 6 months away from qualifying for full retirement, and before he left Steve’s VP office, Jeff had a job working for him on “Special Projects” for 6 months. That’s all you need to know about Steve.

So the team led by Steve, Diane, Dawn, and also Julie and Jim was a draw. Also, the decision had finally been made to fold in the NeuroScience Division, which was formed by SmithKline Beecham some years ago and continued to operate independently despite the merger of Glaxo Wellcome and SKB. The combined teams from NH and NS made for a potent group of talented Specialty Reps selling Lamictal, Requip, Wellbutrin, and PaxilCR.  I took the job under a great Regional Vice President Paul F., from NY who I got along with famously.

Lamictal went on to do quite well along with other newer anticonvulsants like Keppra and Topamax. They were all fine products, much better than the older stuff, but Lamictal topped the others in sales. Lamictal was a challenging and wonderful drug to promote for the treatment of epilepsy, but this was just half the story as a tremendous sales jump was looming with an FDA approval secured for a seemingly unrelated indication.

BIPOLAR DISORDER

Bipolar Disorder, which is surprisingly common (more than 3 Million US cases per year) and not very easy to treat, is characterized by episodes of mood swings ranging from depressive lows to manic highs. The mania is usually easy to spot and there are many effective treatments. Depressive episodes of Bipolar are tricky because usual treatments for Depression (more accurately called Major Depressive Disorder) will often not work, and can actually drive bipolar patients from depression all the way into manic states. Although Lamictal had little apparent impact on mania in bipolar patients, larger clinical trials demonstrated significant mood stabilizing benefit against the depressive symptoms of Bipolar. Today there are a few drugs that are good for this, but in the 2000s, Lamictal was unique. And Psychiatrists welcomed it with open arms. They are generally open to trying new things and the free 6-week titration dosing kits, which start low and increase dose slowly, gave them confidence to prescribe despite the Black-Box Warning. The Bipolar Disorder indication helped catapult annual sales well over two billion dollars within a few years.

I made a great decision joining the NeuroHealth Division. The Representatives were amazing and within 3 years the folks I worked with drove our Region from 30^th to 4^th in the nation, and several Reps and I went on a great Reward Trip. The next year, in 2006, we ran wire to wire in #1 of 39 spots in the NH Division. I went with many of my Reps on another trip of a lifetime. Life is Good. My NH experience propelled my career to the next level, and I am forever grateful.

Lamictal, now generic, remains a popular choice for Epilepsy as well Bipolar Disorder. It was one of the most rewarding products I was associated with in my career.

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