The pharmaceutical world went into shock on August 6, when Pfizer, Johnson & Johnson, and Elan Pharmaceuticals pulled the plug on bapineuzumab (“bapi”), a highly anticipated experimental drug they were co-developing to fight Alzheimer’s disease. The folks at Watertown, MA-based EnVivo Pharmaceuticals were among those watching the drug’s demise with interest. Just a few weeks earlier, EnVivo presented impressive results from a mid-stage trial of its own Alzheimer’s compound, and set out to plan the pivotal trial that will be necessary to win FDA approval. Executives there are undaunted by the bapi disaster. “Our positive study has encouraged us,” says Dana Hilt, EnVivo’s chief development and medical officer.
EnVivo’s compound, called EVP-6124, is in a class of drugs known as alpha-7 nicotinic agonists. Unlike bapi, which was designed to combat the amyloid plaques that form in the brains of Alzheimer’s patients, EVP-6124 works by enhancing transmissions between synapses in the brain. In EnVivo’s recent trial, which was presented at an Alzheimer’s Association conference in July, the highest dose of the drug produced statistically significantly improvements in cognition, memory, and daily functioning.
About half the patients in EnVivo’s trial were taking existing Alzheimer’s treatments, such as rivastigmine (Exelon) or donepezil (Aricept), along with the experimental compound. The other half were not, Hilt says. Both groups were then randomized to either take EVP-6124 or a placebo.The positive effects were seen regardless of whether patients were taking the combination of EVP-6124 and existing drugs or EnVivo’s treatment alone, Hilt says.
EnVivo is currently in discussions with the FDA and European regulatory officials on the design of the pivotal trial, which the company expects to start in 2013. Hilt anticipates the design will be much like that of the recent trial. “We ran it to mimic what a practicing physician who runs an Alzheimer’s clinic or even a geriatrician would see in their practice—a mixture of mild and moderate Alzheimer’s patients, some on [existing treatments] and some not,” he says. “It’s a dress rehearsal, if you will, for the next phase.”
The larger trial may shed light on some of the nuances seen in the recent trial, Hilt says, including one test where patients did not show a statistically significant improvement in symptoms. That test is called the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL). “It’s an inventory that shows whether patients can brush their teeth by themselves, dress themselves, wash themselves, etc.,” Hilt says. Although there wasn’t an overall improvement, mild patients did seem to show a bigger improvement while taking EVP-6124 than more severe patients did, he says. “We have yet to determine whether we will be using [ADCS-ADL] in the larger study. We need to study this more carefully. Or we may need to refine the way in which we capture the data.”
EnVivo is also testing EVP-6124 in schizophrenia patients. It will initiate a pivotal trial in that disease this fall, Hilt says, which will include about 1,500 patients. The company announced positive results from its mid-stage schizophrenia studies late last year.
Most biotechs these days would be looking for deep-pocketed pharma partners right about now, especially those with two late-stage trial programs running simultaneously. But EnVivo has one asset that other startups don’t have: one very patient investor. In 2008, Fidelity Biosciences invested $65 million in EnVivo’s Series D round and bought out all the existing investors, which included BCM Technologies, Cogene Ventures, and NeuroVentures Capital. “We are fortunate that we have an investor who is interested in ‘going long,’ says Kees Been, EnVivo’s CEO. “That allows us to build an integrated company that discovers, develops, and ultimately commercializes products.”
That’s not to say EnVivo won’t consider taking on a partner at some point, Kees says. “We are currently looking at all our options,” he says. “It is true that commercializing around the world is too big a challenge for a small company like ours. So we’re looking at which geographies or indications we should keep for ourselves, and which we should partner or license.”
EnVivo is also advancing a handful of compounds in its early-stage pipeline, including EVP-6308, which inhibits a brain enzyme called phosphodiesterase. Hilt says the company is evaluating the compound’s potential in schizophrenia and other diseases of the central nervous system. And EnVivo is making progress on EVP-0962, which is in an emerging class of Alzheimer’s treatments called gamma-secretase modulators.
As for bapi, Been says he’s not ready to close the lid on its coffin quite yet. “There will no doubt be people who are skeptical now about the amyloid hypothesis, but I believe it hasn’t yet been properly tested,” he says. “Interfering with the amyloid process when you diagnose the patient is too late.” Been predicts other companies will continue to look for ways to make anti-amyloid approaches work, and if they succeed, EnVivo will find its place among those therapies. “We hope our drug works in all patients, irrespective of how much amyloid they have,” he says.