First impressions matter—especially when submitting an Investigational New Drug (IND) application to the Food and Drug Administration (FDA). This would be Genentech’s first so it had to be done right; they couldn’t start clinical trials without it. Everyone from the scientists to the CEO pitched in—some writing to describe the science or the manufacturing processes, some editing on antiquated word processors, others photocopying and stuffing binders. Everything was moving along nicely until the head of regulatory affairs, Sandy Ronspies, broke the bad news. “We can’t get our manufacturing license without someone with pharmacy credentials on staff—it’s a California State rule.” The group was despondent; the submission would be delayed. But Ronspies had an idea: if someone on the team could pass the exam administered by the Board of Pharmacy for this certification, they’d be back on track. For the next week, she and four other employees crammed for the test in the hope that at least one of them would pass. They all did.
It was just one of many unexpected hurdles that the young start-up had to overcome as it attempted to bring its very first medicine to market. Though Genentech had achieved significant early successes with somatostatin and human insulin, it had yet to prove its ability to move that scientific achievement out of the lab and into the critical next phase: large-scale manufacturing, conducting clinical trials, and securing FDA approval. And with that mission in mind, the company set its sights on human growth hormone (HGH).
Partners for Growth
HGH is produced naturally by the pituitary gland. If this gland does not produce enough growth hormone, a child may not reach their full growth potential. In the 1970s the only alternate source of the hormone was pituitary extract from human cadavers, but supply was limited, which meant only the most severe cases received treatment.
Genentech founder, scientist Herbert Boyer, first heard of the concept of treating children with HGH when his own son, who was on the lower end of the growth curve was tested for the deficiency. It was the first time he imagined the real-life potential of recombinant DNA technology. “You know, we could make human growth hormone,” he remembers telling his wife. “All we have to do is isolate the gene."
Boyer and co-founder Bob Swanson managed to convince Swedish pharmaceutical company Kabi, the leading supplier of human HGH at the time, that they could produce recombinant HGH, which could help alleviate the supply problem. Swanson’s hope was that the deal—which reserved U.S. marketing rights for Genentech—would help establish his fledgling business as a fully-fledged company.
Soon after the team of scientists, including Dave Goeddel and Herbert Heyneker, succeeded in producing HGH in the lab, Swanson hired Bill Young to lead development of HGH manufacturing. Young had just finished working on the scale-up and production of human insulin at Eli Lilly and his experience would prove vital in navigating the challenges ahead—from scaling up manufacturing facilities to passing FDA inspections, but perhaps most significant of all: addressing the issue of safety.
Eager to begin clinical trials as soon as possible, Genentech employees did something surprising that would never be allowed today: twenty people volunteered to participate in the Phase I safety trial. It was perhaps indicative of the nascent company’s culture—enthusiastic employees excited to bring their first medicine to patients as fast as they could. But spirits were soon dashed as it became clear that something was wrong. Some of the volunteers experienced adverse reactions to the recombinant HGH, including fever and chills.
The team soon realized that there must be undetectable remnants of fever-inducing pyrogens from the E coli bacteria in which the HGH had been expressed. The clinical trial was immediately suspended and Young’s team had to begin the labor-intensive work of simultaneously improving the purification and analytical techniques to ultimately eliminate the contaminants.
It was a stark wake-up call for the company. Producing a safe and effective medicine on a large-scale would be just as complex as those early scientific breakthroughs in the lab. As Boyer later remarked, “The absolutely amazing thing to me was the manufacturing component of the industry which had to be developed. It was totally new. It wasn’t fermenting beer. It wasn’t making antibiotics. It was completely different.”
Genentech received FDA approval of its first medicine, Protropin® (somatrem for injection), on October 18, 1985—and not a moment too soon. Just six months earlier, all existing stocks of pituitary gland HGH had been pulled from the market after a rare and fatal viral contamination was discovered. After almost a decade in business, the company had finally succeeded in realizing the potential of recombinant DNA technology to directly impact people’s lives with its own medicine.
Genentech's Protropin® (somatrem for injection) ceased production in 2004. Its successor, Nutropin AQ® [somatropin (rDNA origin) for injection], was introduced to the market in the same year.
What it Treats
WHO IS NUTROPIN THERAPY FOR?
Nutropin AQ® injection for subcutaneous use is a human growth hormone that is available by prescription only.
Doctors prescribe Nutropin therapy for children and teenagers who are short or growing slowly because they:
- Do not make enough growth hormone on their own.
- Have idiopathic short stature, which means they are shorter than 98.8% of other children of the same age and sex; are growing at a rate not likely to allow them to reach normal adult height; and no other cause of short stature can be found.
- Have Turner syndrome.
- Have chronic kidney disease (CKD) up to the time of kidney transplant.
Doctors prescribe Nutropin therapy for adults who have growth hormone deficiency that began either in:
- Adulthood as a result of pituitary disease, diseases of the hypothalamus, surgery, radiation therapy, or trauma; or
- Childhood. Patients treated for growth hormone deficiency in childhood, whose bones have stopped growing, should be reevaluated to see if they need to continue with growth hormone therapy.
Your doctor will test to see if growth hormone is right for you.
Important Safety Information
Nutropin therapy and your safety:
Please read this Important Safety Information carefully. Then, if you have any questions, talk with your doctor.
NUTROPIN THERAPY IS NOT FOR:
- Patients having serious complications after undergoing open heart surgery, abdominal surgery, serious injuries involving many body systems, or life-threatening breathing problems. Deaths have been reported in such cases.
- Children who have Prader-Willi syndrome (PWS) and are very overweight or have a history of severe breathing problems. Deaths have been reported in children with PWS who are very overweight, have a history of blocked upper airways, sleep apnea (pauses in breathing during sleeping), or other severe breathing problems.
- Patients who have active cancer. Because growth hormone deficiency can be an early sign of some tumors in the brain or pituitary gland, the presence of these types of tumors should be ruled out by your doctor before you start Nutropin therapy.
- Patients who are allergic to somatropin, the active ingredient in Nutropin therapy, or the inactive ingredients in Nutropin therapy.
- Adults or children with certain types of eye disease caused by diabetes.
- Children and teenagers whose bones have finished growing.
What should you tell your doctor before starting Nutropin therapy?
- If you take cyclosporine, hormone replacement therapy, insulin or other diabetes medications, drugs containing steroids, or drugs for seizures. These medications may need to be adjusted during Nutropin therapy.
- If you had cancer as a child. An increased risk of a new tumor, particularly certain brain tumors, has been reported in patients taking Nutropin therapy. If you have pre-existing tumors or growth hormone deficiency caused by abnormal tissue in the brain, you should be watched closely for the worsening or return of this condition.
- If you have diabetes, risk factors for diabetes, or impaired glucose tolerance. If so, your doctor should monitor your blood sugar closely during Nutropin therapy. New cases of type 2 diabetes have been reported in patients taking Nutropin therapy.
- If you have pituitary hormone deficiency(s) (an inability of the pituitary gland to produce sufficient hormones) or adrenal hormone deficiency (an inability of the adrenal glands to produce sufficient hormones, primarily cortisol). Your doctor may further monitor your hormone levels or your hormone replacement therapy closely while you are taking Nutropin therapy.
- If you are pregnant, nursing, or plan to become pregnant. It is not known whether Nutropin is excreted in human milk. Nutropin therapy should be used during pregnancy only when clearly needed.
While taking Nutropin, contact your doctor immediately if you experience:
- Changes in upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, in patients with PWS. These patients should also have effective weight control and be monitored by a doctor for signs of respiratory infection.
- Changes in vision, a bad headache, or nausea with or without vomiting. This may be a sign of increased pressure in the brain.
- Any allergic reaction you experience to the injection of Nutropin therapy.
- A limp or have hip or knee pain.
- A fracture in the ball of the hip joint can occur in children who have endocrine problems and in children who have rapid growth.
- Children with growth failure due to CKD should be examined periodically for evidence of loss of bone minerals. Hip x-rays should be taken before starting Nutropin therapy in these children.
- Progression of scoliosis (curvature of the spine) that can occur in children who have rapid growth. Nutropin therapy has not been shown to increase the occurrence of this condition.
- Increases in laboratory test serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone (PTH), or IGF-1.
- Abdominal pain. Cases of pancreatitis (inflammation of the pancreas) have been reported rarely in children and adults receiving Nutropin therapy .
Other important information about Nutropin
- Adults may retain water during Nutropin therapy. This may be brief but may increase with higher doses of Nutropin therapy.
- Patients should have their thyroid function tested periodically during Nutropin therapy. Thyroid hormone treatment may need to be started or adjusted.
- Patients should be sure to inject Nutropin at a different recommended place on their body each time to avoid tissue breakdown. A doctor or nurse should provide injection training and supervise the first injection.
- The use of Nutropin therapy has not been studied in patients over 65 years of age. Elderly patients may be more sensitive to Nutropin therapy and may experience more side effects.
- Patients with Turner syndrome should be monitored closely by a doctor for ear infections and cardiovascular problems during Nutropin therapy.
What are common possible side effects of Nutropin therapy?
Common side effects reported in adults and children taking Nutropin therapy include injection site reactions. Additional common side effects in adults include swelling, joint pain, and carpal tunnel syndrome.
You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.
How should you store Nutropin?
Nutropin must be kept refrigerated (36° to 46°F [2° to 8°C]). Do not freeze. Cartridges and NuSpin pens must be used within 28 days of initial use. Throw away any unused Nutropin after 28 days of initial use. Before giving an injection, check the manufacturer’s expiration date on the cartridge or pen. Do not use if it has expired. Do not inject medication if the solution is cloudy.
Please see Nutropin full Prescribing Information for additional Important Safety Information.
Title Photo: Genentech had to develop and scale-up the processes by which human growth hormone could be manufactured in quantities sufficient for clinical trials. Photo from Genentech archives.