Startup Relmada Therapeutics (OTCQB:RLMD) is in the enviable position of having multiple shots on goal in the world’s largest drug prescription market: the treatment of pain.
“It is very unusual for a startup or even a mid-sized biotech company to have four different medications in clinical development for pain relief,” Dr. Eliseo Salinas, president and CSO, says in an interview with BioTuesdays.com.
“Our robust portfolio includes three products that combine proven drug candidates with novel delivery methods to create new drugs for new indications, while our fourth is a new entity, which offers significant upside,” he points out. “We target every level of the chronic pain spectrum.”
Dr. Salinas explains that Relmada’s portfolio mitigates development risk through the use of a low cost, low risk 505(b)(2) regulatory pathway, which offers the potential to bring three of its four drug candidates to market faster.
“We expect significant value creation over the next 12-to-18 months due to these accelerated development timelines,” he adds.
Relmada went public in May 2014 through a reverse merger of two private companies. Dr. Salinas, who joined Relmada in February 2014, has an impressive track record of having developed successful drugs at Elan, Shire and Wyeth, including blockbusters Tysabri, Vyvanse, Adderall XR and Effexor XR.
Relmada’s current portfolio includes:
REL-1015 (levorphanol ER), a once-a-day extended-release, abuse-deterrent formulation of the potent opioid, levorphanol, which is also a serotonin–norepinephrine reuptake inhibitor (SNRI) and N-methyl D-aspartate (NMDA). It is expected to enter a Phase 3 program, in the next 12-to-18 months, for the treatment of chronic pain when an opioid is needed.
REL-1017 (dextro-Methadone) is a d-isomer of methadone but, unlike the parent molecule, inhibits pain through antagonism at the NMDA receptor. It is substantially devoid of opioid side effects and should enter a Phase 2 trial in the first half of 2016.
REL-1028 (oral buprenorphine, BuTab), if approved, would be the first oral tablet of buprenorphine on the market for the treatment of chronic pain and addiction. It is expected to enter Phase 1 development in April 2015.
REL-1021 (topical mepivacaine) is a topical gel form of the local anesthetic, mepivacaine, for the treatment of postherpetic neuralgia and HIV-associated neuropathy. It should enter Phase 1 studies later this year.
In February, Maxim Jacobs, an analyst with Edison Investment Research, initiated coverage of Relmada, with a value of $601-million or $11.56 a share. The stock closed at $2.80 on Friday.
Citing the $13-billion-a-year prescription pain market, Mr. Jacobs said, “If even one of Relmada’s products reaches the market, the current valuation could be easily justified.”
While lead product LevoCap ER, or REL-1015, could be used in a large variety of pain indications, Mr. Jacobs pointed out that dextro-Methadone, BuTab and MepiGel each have unique qualities that could differentiate them in a crowded pain market.
According to Dr. Salinas, REL-1015 is pharmacologically differentiated from morphine, oxycodone and other strong opioids. The dosage form being considered would be a small, once- or twice-daily extended-release capsule, which would be abuse and tamper resistant.
“Levorphanol’s multi-modal mechanism of action provides for a more robust efficacy profile and potentially could be used alone for patients who take multiple drugs,” he contends. “Current prescribing habits show that opioids are generally prescribed in combination with other pain relievers in approximately 90% of patients.”
Relmada has conducted an independent market survey with about 150 physicians specializing in pain management. Dr. Salinas says that after learning about REL-1015’s multi-modal mechanism of action, 75% of physicians interviewed showed a high interest in using a new form of levorphanol.
The company’s three other products—dextro-methadone, oral buprenorphine and topical mepivacaine—target neuropathic pain, which affects some five million people in the U.S., with very few and only modestly effective treatment alternatives.
“dextro-Methadone represents a potential blockbuster drug to treat neuropathic pain, without the addiction hazard of methadone and other side effects, such as constipation, nausea, drowsiness and respiratory depression,” Dr. Salinas contends. “One of our goals is to show that dextro-Methadone is not methadone.”
Last month, the company reported positive results in the first part of a Phase 1 study of dextro-Methadone. It demonstrated a good safety profile, with no dose-limiting side effects after four cohorts were exposed to increasingly higher doses. “We administered doses of dextro-Methadone that would not be possible with methadone,” Dr. Salinas says.
In the second part of the study, healthy subjects will receive higher daily doses of dextro-Methadone in order to determine a maximum tolerated dose, prior to a Phase 2 proof-of-concept study in neuropathic pain.
Relmada’s oral buprenorphine represents the first form of buprenorphine in a tablet that can be swallowed for use in chronic pain and treating addiction. Existing forms of buprenorphine are administered by injection, a patch or sublingual films. “We have found a formulation strategy that allows buprenorphine to be taken by mouth,” Dr. Salinas says.
According to the U.S. Drug Enforcement Administration, buprenorphine is a schedule 3 opioid, with a lower potential for abuse, compared with Schedule 2 opioids, such as oxycodone and fentanyl. No schedule 3 extended-release opioids are marketed in the U.S. now.
In addition to the lower risk of abuse, schedule 3 opioids have other practical advantages over schedule 2 opioids. Prescriptions for schedule 2 drugs cannot be refilled, and a new prescription must be issued each time. In contrast, prescriptions for schedule 3 drugs may be refilled up to five times in six months. Prescriptions for schedule 2 drugs must be written and signed by the physician, while prescriptions for schedule 3 drugs may be written, phoned-in or faxed.
Last year, Vicodin, a short acting and widely used hydrocodone/acetaminophen combination, was upgraded from schedule 3 and became a more restricted schedule 2 drug. This enhanced the commercial potential for oral buprenorphine, Dr. Salinas suggests.
Relmada’s third candidate for neuropathic pain is REL-1021, or topical mepivacaine, which has the potential to be the first topical gel dosage form of any local anesthetic. It has two orphan drug designations from the FDA for the management of postherpetic neuralgia, a chronic pain following shingles infection, and the treatment of painful HIV-associated neuropathy, a burning sensation in the extremities caused by HIV infection and HIV drugs.
Dr. Salinas suggests that REL-1021 has the potential to be used alone or in combination with oral pain therapies, such as Lyrica and Cymbalta, providing significant market potential.
If approved, REL-1021 will compete directly with the Lidoderm Patch, which had peak sales of nearly $1-billion, he adds, noting that Relmada is also developing a spray version of mepivacaine.
“The potential advantages of our product over the Lidoderm patch include greater skin penetration and skin retention. Plus it is easier to use than a patch and much more convenient for patients,” Dr. Salinas contends.