With Dr. Alan Sachs of Merck and Dr. Sean Harper of Amgen

May 18, 2009 – 10:21 pm by Chris

I had two interviews this afternoon at BIO 2009; one with Dr. Alan Sachs, VP, RNA Therapeutics, Merck Research Laboratories, and Dr. Sean Harper, chief medical officer and senior VP of global development, Amgen.

Both do have something in common other than being at BIO 2009. “Oh, I know Alan!” Dr. Harper said when I told him I had just come from that interview. “I hired him when he came to Merck from the University of
California.” (For those who can’t quite remember or don’t feel like using Google, Dr. Harper was originally was senior director of clinical genomics at Merck Research Labs before being recruited to Amgen by Dr. Roger Perlmutter, who left Merck in 2001 to become executive VP of research and development at Amgen. Dr. Harper followed Dr. Perlmutter to Amgen in 2002).

For more on Dr. Sachs’ background, you can read his official executive profile.

When I sat down with Dr. Sachs to hear about Merck’s RNA research program, I was hoping for a hint of what’s in Merck’s pipeline, either RNA drug candidates or drugs with targets that were validated through RNA research. But Merck’s infamous caginess about what exactly is in its pipeline stifled those hopes. Outside of Merck’s three-times-a-year analysts meetings, the company does not talk about what’s in its pipeline, Dr. Sachs says.

And with the Schering-Plough merger with Merck, “that’s going to be the topic of analysts’ meetings for a long time to come,” Dr. Sachs says.

Although he could not specify what RNA-related drugs Merck has in its pipeline, Dr. Sachs did talk about the two directions Merck is taking with RNA research. Merck is working on RNA-based therapeutics, but is trying to tackle the problems of delivering RNA to cells. The company has been working on a lipid delivery system that is rapidly taken up by the liver. Because of the effectiveness of this delivery mechanism, Merck hopes to develop medicines for hepatocellular carcinoma (liver cancer) and hepatitis C.

But most of all, Merck wants to make sure these RNA therapies are safe. “That’s the area that will differentiate Merck from others three or four years from now,” Dr. Sachs says. “Everyone else is focusing on delivery, but potency is not the hardest part of the delivery problem, it’s safety. By safety here, we mean it’s not enough to give a single dose of a drug to a terminally ill patient, it must be able to be taken by patients with a chronic disease on an everyday basis.”

Merck is also using RNA to better determine disease targets for drugs, A bigger stable of validated drug targets gives Merck the luxury of choosing which ones to focus future testing on, Dr. Sachs says.

But don’t expect Merck’s pipeline to suddenly swell. “The cost of developing a drug hasn’t changed,” Dr. Sachs says. “Our goal is to increase the probability of success. I think you will see an increase in our Phase III rate of success.” Even a 15% to 25% increase in success would be significant.

And the Schering-Plough deal does have one bonus for the RNA group, Dr. Sachs says. “The wonderful thing about an acquisition, a tool of this power benefits everyone when people use the information,” he says.”Now that we’ll have a larger research unit, there will be more people using it. All of us at Merck, working in these different platforms, we love having more colleagues to share the data.”

Although corporate policy and general policy blocked Dr. Sachs from discussing Merck’s pipeline, Dr. Harper had no such inhibitions in talking about Amgen’s up-and-coming drugs. One of the biggest stories at Amgen still remains denosumab, a fully human monoclonal antibody that specifically targets the RANKL ligand. Amgen’s new drug application for denosumab in the treatment and prevention of postmenopausal osteoporosis in women and treatment and prevention of bone loss in patients undergoing hormone ablation therapy for either prostate or breast cancer has been accepted by FDA. The company expects FDA advisory commitee hearings during the summer and if all goes well, approval either at the end of 2009 or the beginning of 2010.

But Amgen wants to be known for more than denosumab, Dr. Harper says. The company has been collaborating with UCB Pharma on sclerostin Ab, a humanized antibody that targets sclerostin, a protein secreted by bone cells that inhibits bone formation. It’s been shown that humans who are deficient in sclerostin have extremely dense, fracture-resistant bones. “In one case in South Africa, ER physicians noticed that a family in a car accident had serious injuries but no fractures,” Dr. Harper says. Dr. Harper says the ER surgeon brought in a geneticist to figure out what had made this family’s bones so strong; the geneticist found the sclerosiin deficiency, and Amgen learned of the research.

Phase II trials for sclerostin Ab in osteoprosis should be starting soon, Dr. Harper says.

Amgen’s focus on osteoporosis is a practical one, Dr. Harper believes. “In general, the burden of illness in respect to osteoporosis is getting to be very well recognized,” he says. “Not really appreciated is how poor are the treatment paradigms.” Oral and intravenous bisphosphonates are inconvenient and can cause unwanted side effects, such as esophageal irritation (for the oral drugs) and flu-like symptoms (for the intravenous ones). Also, most primary-care offices are not set up to administer intravenous bisphosphonate therapy. Thus, patients might fill their prescriptions, but because the benefits are silent, patients do not adhere to the therapy. A drug such as denosumab, which is given twice yearly as a subcutaneous injection, fits in better with patients’ lives, Dr. Harper says.

Outside of osteoporosis, Amgen is excited about its cancer pipeline, Dr. Harper says. There is AMG 386, a peptibody molecule that tackles a different antiangiogenic pathway in cancer. The drug is in Phase I trials. “We’ll be seeing data this year for breast cancer, gastric cancer, and renal cell cancer,” he says. The company hopes to understand how the inhibition exhibited by AMG 386 compares with the better known VEGF pathway, and is optimistic that AMG 386 will show broad applicability across many tumor types.

Another drug expected to work on a wide mechanism is AMG 655, which targets death receptor 5 and induces apoptosis in sensitive tumor cells. And there is AMG 951, a ligand that also regulates apoptosis. The drug is the focus of a collaboration with Genentech.

Amgen is also working on several asthma drugs, in Phase II development. AMG 761, an anti-CCR4 humanized monoclonal antibody in-licensed from Kyowa Hakko, binds to CCR4 sensitive T cells that cause an inflammatory response in asthma. Dr. Harper says the drug is designed to deplete these cells when administered in very low concentrations, and in tests the company has seen “very profound and long-lasting clearing of these cells.”

The acquisition of Tularic brought in AMG 853, an orally adminstered small molecule antagonist of the receptors of prostaglandin D2. The company expects to inititate Phase II trials in asthma soon, Dr. Harper says.

With all of these drugs, Dr. Harper expressed optimism for Amgen’s future. “It’s certainly going to be an exciting several years of data generation,” he says.