For the last 20 years, the pharmaceutical industry has marketed no new drugs in the fight against Alzheimer’s disease. Alzheimer’s patients have had very few options for treating the condition, which slowly and surely robs them of their memories and mental faculties, and ultimately their lives. In 1996 the FDA approved Aricept, a cognition-enhancing drug that modestly improves patients’ ability to think, but which does little to slow the deadly progression of the disease. However, in the meantime, researchers have been looking for drugs that could add new weapons to the medical arsenal against Alzheimer’s. One of those companies, Monmouth Junction-based Suven Inc., is now looking for test subjects in a clinical trial for one such drug.

Suven recently began a clinical trial for SUVN-502, a drug that enables the two standard drugs given together for Alzheimer’s, Aricept and Namenda, to function longer by increasing the amount of acetylcholine in the brain.

More than 5 million Americans, including 170,000 in New Jersey, have Alzheimer’s disease, a progressive brain disorder that slowly destroys memory and thinking skills, according to the Alzheimer’s Association.

“It is important to increase awareness of Alzheimer’s disease and the fact that drugs on the market do not prevent progression of the illness. They only do so much and stop working after a while,” says Jeffrey Apter, medical director and president of Princeton Medical Institute, senior attending physician at University Medical Center of Princeton at Plainsboro, member of the scientific advisory board of the New Jersey Alzheimer Association, and investigator for the SUVN-502 trial. He suggests that SUVN-502 may prevent further progression of the disease.

One reason that few treatments are available for Alzheimer’s is that the cause of the disease is still poorly understood despite decades of research. However, scientists have observed that Alzheimer’s is always accompanied by certain changes in the brain, and Suven’s drug is part of a class of medications that seek to treat Alzheimer’s by treating one of those changes.

With the progression of Alzheimer’s (and in normal aging as well), acetylcholine, a neurotransmitter in the brain essential for processing memory and learning, gets depleted. Suven’s drug, SUVN-502, is meant to increase levels of this neurotransmitter.

Although neurotransmitters need to be degraded somewhat in the body, because they will be toxic if they accumulate, Suven’s chief executive officer, Venkat Jasti, says you have to have “enough of a concentration in the brain so you have a cognitive effect.”

Apter says that both animal studies of SUVN-502 and early human studies, where the drug is administered for a short time, showed that SUVN-502 improved cognition — the ability to learn — and memory. Apter adds that simply increasing the amount of acetylcholine in the brain may itself may have some effect on improving cognition.

“Alzheimer’s is reaching epidemic proportions, especially associated with the aging of the baby boomer generation, and we are looking for new pharmaceuticals which will help improve our treatment of Alzheimer’s,” Apter says.

He emphasizes the importance of coming in for early testing. “The earlier we start medications for these patients the better,” Apter says.

For the clinical trial to examine the efficacy and safety of SUVN-502 on mental abilities impaired by Alzheimer’s, Suven is seeking 530 patients, ages 50 to 85, who have had a diagnosis of moderate Alzheimer’s disease, have had the disease for at least a year, and are taking both Aricept (Donepezil) and Namenda XR (Memantine).

Moderate Alzheimer’s disease means that a patient is already having symptoms, including both memory problems and difficulty with daily tasks. Examples of impaired functioning, Apter says, are when “the person used to do the checkbook but can’t do it anymore, used to play a mean game of bridge but can’t do it anymore, or was a super cook but now has trouble remembering recipes.”

One requirement of the study is that patients come in with a caregiver who can provide an accurate assessment. “Sometimes a patient is not able to give an objective picture of what they are doing,” Apter says, adding that the caregiver can be friend, a paid caregiver, or someone in the same retirement community as long as the person spends time with the patient every week.

“It doesn’t have to be a burden on the kids,” he adds, noting that generally patients have no trouble bringing in a caregiver.

The study is spread over 90 clinical sites in the United States, and each patient will undergo treatment for six months.

Princeton Medical Institute (PMI), an investigative research organization that conducts clinical trials in the areas of psychiatry, neurology, and general medicine, is looking for a total of 20 qualifying patients in New Jersey. “It is always hard to find patients who exactly qualify — they have to be in the exact range of the study on the cognitive/memory scale,” Apter says.

And there are other challenges. Although area doctors say they have good patients, many patients are resistant. “They are in denial or their families are in denial,” Apter says.

Also, Apter says, “some people think they may be guinea pigs.”

“There is a lot of ignorance about what is involved in a clinical trial,” Apter says, explaining that “people have to know their safety comes first.” As the trial continues, his center provides a lot of support for patients and families, and it evaluates the patient regularly, with blood work on each visit, looking carefully for any side effects or changes in blood work or EKGs.

Apter touts the free medical care people receive during a clinical trial. “Where else in New Jersey can you see a doctor for free, get blood work for free, and a psychological assessment for free?” Apter says.

Also, as part of a trial, they have access to experimental drugs not yet approved by the FDA.

Finally, he says, “there is an altruistic reason to participate — to move the field further. We can’t get new drugs to market without people participating in clinical trials.”

Princeton Medical Institute offers free memory testing for anybody in the community, any day of the week, in its offices at 256 Bunn Drive in Princeton (609-921-6050, www.princetonmedicalinstitute.com) and invites people to come in to learn about Alzheimer’s and about the SUVN-502 study. PMI can also make the diagnosis of Alzheimer’s disease.

PMI has been involved in trials for every successful Alzheimer’s drug brought to market: Cognex, Aricept, Exelon, Rivastigmine, and Namenda. If patients do not qualify for this particular study, Apter says, Princeton Medical Institute is running other studies they can enter.

Jasti founded Suven in 1989 as a manufacturer of bulk active pharmaceutical ingredients that go into the formulation of drugs, but are not specific to any therapeutic activities, after working for about 15 years as a registered pharmacist in New Jersey and New York. In 1995, Suven added contract research and manufacturing services (CRAMS) to its services.

Because active pharmaceutical ingredients do not have intellectual property protection, Suven in 2005 embarked on in-house drug discovery “to get into the supply chain of innovative companies who are developing new drugs,” Jasti says.

In 2006 Suven became the first company from India to collaborate in drug discovery with Eli Lilly on a partial funding and sharing basis. They provided the drug targets, and Suven worked on developing a clinical candidate, in close collaboration with Eli Lilly scientists. After Eli Lilly had to pay a $1.4 billion criminal fine in 2009 for illegally marketing the antipsychotic medication Zyprexa, the company cut down its portfolio, but Suven continued to develop the molecule it had created during the collaboration. Suven has 13 drug candidates in its pipeline, about half related to cognition and the rest to pain and major depressive disorder.

Jasti chose the central nervous system (CNS), the second largest and fastest growing therapeutic category, as the target for its development efforts. Noting that CNS drugs target a “highly unmet medical need,” Jasti adds that is also one where success is a rarity. “When you are a small player, you need to do something that is more difficult to get a result out of it so you can be easily partnerable,” he says.

Many other companies have been working on the 5-HT6 target, and although there have been may clinical trials that have gone up to phase 3 (when a drug is given to large groups of people to confirm its effectiveness, to monitor side effects, to compare it to commonly used treatments, and to collect information that will allow the drug or treatment to be used safely), they have failed based on toxicity and not having enough efficacy. As of today, no drug has come out of this target.

Having tested SUVN-502 against competitor molecules in lab animals, Jasti says, “we feel our molecule is much better in efficacy and in safety.” Because these molecules have to work atop of the two standard Alzheimer’s medications, they have had problems with efficacy or toxicity. “Suven is the first molecule that goes on top of both molecules in chemical trials without any side effects but with a synergistic efficacy effect,” Jasti says.

Based on the animal trial data, Suven set up a human trial starting in October, 2015, and has already enrolled more than 160 patients, half of whom have already finished their study. It is a double blind study, with the data locked into a database until the last patient is done. The trial uses two separate doses of drugs and also a placebo, which is the standard of care with the two generic drugs.

Suven Life Sciences, headquartered in India, is a publicly traded company with $100 million in sales. All the clinical development and phase 1 and 2 trials are done under the Monmouth-based, Suven, Inc., which has 10 employees. The clinical trials are outsourced through a contract research organization in Boston.

Out of more than 750 projects, six have gone into commercial production. Suven employs 900 people, of whom 380 work in research and development, and 38 have PhDs.

In addition to Alzheimer’s, Suven is working on a dozen drugs for cognitive deficiencies in ADHD, Parkinson Disease, schizophrenia, pain, and major depressive disorder.

Apter grew up in Johannesburg, where he went to medical school. He did his psychiatric training at Washington University in St. Louis and has lived in the Princeton area for 30 years. His father was a physician and his mother a school teacher. He has a private practice in psychiatry, where he does medical management of psychiatric illnesses and psychopharmacology.

Jasti’s parents are farmers. He received a master’s degree in pharmacy in India, moved to the United States in 1974, and got another master’s at St. John’s University. When he came to the United States, he was already thinking of doing research, but the economy was bad and he realized he needed to just find a revenue-generating position for himself, so he became a pharmacist. But he always had research in mind, and after a decade or so decided that was what he wanted to concentrate on. So he started with manufacturing services, then moved to drug discovery, and, he says, “I hope to have success in the near future for a drug for an unmet medical need.”

SUVN-502, Jasti says, “paves the way for a collaborative opportunity. We aim for a partnership with a big company.”

Suven Life Sciences USA LLC, 1100 Cornwall Road, Suite 110, Monmouth Junction 08852. 732-274-0037. Jasti Venkat, president & CEO. www.suven.com.

Princeton Medical Institute, 256 Bunn Drive, Princeton 08540. 609-921-6050. www.princetonmedicalinstitute.com.

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