Alkermes Moves Beyond Reformulations As It Preps Three New Compounds For Clinic

Alkermes multi-year efforts to move up from its successful reformulations for partners takes a step forward as the biotech presents its expanding clinical pipeline to investors, highlighting early-stage compounds for multiple sclerosis, pain and cancer.

For Alkermes PLC, the value proposition lies in using its knowledge in drug delivery and formulations to make a new slate of pipeline candidates – in particular, drugs that rely on proven blockbusters but provide further benefits to patient experiences. The Dublin and Waltham, Mass.-based biotech announced at an R&D day on July 17 the addition to its pipeline of three new drug candidates, which it believes it can effectively differentiate in the marketplace.

It’s easier to advance pipeline drugs quickly when you are working off the assumption that the drugs are already proven effective, CEO says.

Alkermes expects to have three new drugs in the clinic by mid-2014, fleshing out its pipeline to include a total of six drugs. The new entrants include a prodrug of monomethyl fumarate (MMF) for multiple sclerosis, which is based on Biogen-Idec Inc.’s newly launched Tecfidera (dimethyl fumarate), ALKS-7106 for pain, and the cancer immunotherapy RDB-1419.

“We’re playing to win here,” said Alkermes CEO Richard Pops of his confidence in the strategy at the R&D day. Pops outlined the way the company looks at new drugs it is planning to bring into its pipeline – noting that no drug is more important than any other, but that decisions to move forward are data-driven. According to Pops, Alkermes is setting up its drugs to fail early by considering the reality of whether a drug is approvable by FDA and how the drug will be treated by payers, particularly whether payers will want further data beyond that required by regulators. And he’s considering these issues as early as Phase I. “These are questions that a lot of biotechs, and even some Big Pharmas, fail to ask early enough,” said Pops.

Alkermes is focused on chronic diseases that affect broad patient populations underserved by current therapies – pursuing areas typically served by Big Pharma, but with a biotech approach. The company takes a blockbuster that has proven pharmacology and improves dosing or side effects. Pops noted that it’s easier to advance pipeline drugs quickly when you are working off the assumption that the drugs are already proven effective. He believes that modest innovation is no longer enough in the current regulatory and reimbursement environment, and that companies have to have truly differentiated products that offer real-world advantages to patients.

The company’s background in reformulations and drug delivery technology allows it to have a close knowledge of how to effectively improve on drugs. Through its partners, Alkermes has four products currently on the market: the long-acting antipsychotic franchise that includes Invega Sustenna (paliperidone palmitate) and Risperdal Consta (risperidone) partnered with Johnson & Johnson, the walking treatment for multiple sclerosis patients Ampyra (dalfampridine) partnered with Acorda Therapeutics Inc., and the once-weekly GLP-1 diabetes drug Bydureon (exenatide) partnered with Bristol-Myers Squibb Co. and AstraZeneca PLC. It also markets the wholly-owned substance abuse therapy Vivitrol (naltrexone) (Also see "Long-Acting Atypical Antipsychotic Market Snapshot: A One-Company Market Begins To Diversify" - Pink Sheet, 18 Mar, 2013.).

The biotech’s pipeline additions are its latest attempt to transition the company from a drug delivery partner to a drug improver working on its own wholly-owned assets.

Fleshing Out The Pipeline

Alkermes’ latest offering for multiple sclerosis patients will – if all goes well – be an improvement on Biogen’s much-touted Tecfidera (Also see "Biogen Idec’s Tecfidera Goes To Market With Claim For Delay Of Disability Progression" - Pink Sheet, 27 Mar, 2013.), an oral pill that cleared FDA in March and has been a quick success (Also see "Early Drug Launches Off To a Strong Start So Far in 2013" - Pink Sheet, 13 May, 2013.). Alkermes proposes an improvement on dosing – by making a once-daily pill instead of twice daily – and, more important for payers, an improvement on side effects, which could result in fewer trips to health care providers. It expects its prodrug to have fewer gastrointestinal side effects and minimal flushing in comparison to Tecfidera.

The prodrug, an inactive form of the original drug that the body naturally converts to the active form, will be considered a new molecular entity (as will all the new pipeline candidates) and is covered by strong intellectual property, which protects it through 2034. The company is considering advancing two lead candidates in this program. One advantage of developing prodrugs is that since the drug’s mechanism of action is well understood, the Phase I trial, not the Phase II or III trials, is the major risk-lowering study, Pops said in an interview prior to the meeting.

ALKS-7106 will be a new offering to treat chronic pain that has less potential for abuse than current therapies. As Pops explained to analysts, many companies are trying to make similar drugs that have less abuse potential, but are doing this by “wrapping” the opioids in abuse resistance technology that either makes the pill harder to crush or turns it into a gel when dissolved. Yet, these methods don’t stop patients from abusing the medication by swallowing multiple doses. ‘7106, which is 30 times more potent than morphine, is an opioid modulator that has patent protection through 2025.

Another opioid modulator in the company’s pipeline, ALKS-5461, is currently in Phase II and combines the mu-opioid antagonist ALKS-33 and buprenorphine as a treatment for patients who have failed on multiple other depression medications. The company’s opioid modulation platform “decouples” the drug from the euphoria effects typically seen with opioids, allowing for rapid uptake into the brain, then seals the receptor against further neurotransmitter release. The company said the antagonist and agonist in the drug work together to relieve symptoms of depression.

The final addition to the pipeline, RDB1419, is a cancer immunotherapy based on the interleukin-2 pathway. It is meant to be an improvement on Prometheus Laboratories Inc.’s Proleukin (aldesleukin). The company believes that the treatment has been limited to an indication for melanoma by its toxicity effects, an aspect Alkermes believes it can improve on. This drug will be the company’s first biologic and is based on its PICASSO technology, a way of creating a novel fusion protein that links active biologics with its own receptor.

Rounding out the company’s pipeline are a long-acting injectable version of the antipsychotic Abilify (aripiprazole), which the company refers to as aripiprazole lauroxil (previously ALKS9070), and the oral antipsychotic ALKS-3831, a combination of olanzapine (a generic version of Eli Lilly & Co. ’s Zyprexa) and Alkermes’ own proprietary compound ALKS-33. The combo is expected to have the same efficacy as Zyprexa without the weight gain associated with the drug.