Titan Pharmaceuticals has been cleared to start the second phase of a trial of its ropinirole implant for Parkinson’s disease—but will have to postpone it because of financial constraints.
The drug delivery specialist said the phase 1/2 study is proceeding as hoped, and the data and safety monitoring board has recommended it start enrolling a second cohort of patients. That’s being put on hold, however, while Titan tries to build sales momentum for its under-performing Probuphine product for opioid addiction, which has consistently missed sales targets since its launch in the second half of 2016.
The ropinirole implant would be an alternative to daily oral formulations of the dopamine agonist, which is a staple of Parkinson’s therapy and is also used to treat restless legs syndrome. Titan is trying to show that delivering the drug continuously can help prevent some of the muscular side effects seen with oral dosing.
In May, Titan recovered U.S. rights to the product from commercial partner Braeburn Pharma, having booked just $25,000 in royalties earned on net sales of the drug in the first quarter, and just $215,000 in 2017. Last year, it was forced to take out a debt facility to cover development expenses, and ended the year with just under $6 million in cash reserves.
On paper, Braeburn looked like a perfect partner for Probuphine as it is an opioid addiction treatment specialist, but was hit earlier this year by an FDA rejection of its own weekly and monthly depot buprenorphine injections that will be taking up a lot of management time and forced it to slash its salesforce headcount.
Titan’s CEO Sunil Bhonsle said the company remains “very committed to adding value for our stockholders based on achievements with Probuphine and our other … products, such as our ropinirole implant. To that end, we intend to resume enrolling patients in this phase 1/2 trial as resources allow.”
The company still needs to fund a new commercial partner for the U.S., and will also be hoping that a new licensing deal for Probuphine in Europe, where the product is currently under regulatory review, will deliver some of those resources.
The partnership with Italy’s Molteni was signed in March and provides exclusive rights to the drug in Europe and some other countries in the Commonwealth of Independent States, the Middle East and North Africa. Molteni also assumed a chunk of Titan’s debt, alleviating some investors' concerns that Titan was going to struggle to pay it off.
It’s not all going completely smoothly for Probuphine in the EU, however, as the EMA has raised some questions about the dossier. Still, Molteni said it is confident it can answer those and bring the product to European markets.
https://bit.ly/2tSOSe9
Tuesday, July 3, 2018
No, Massachusetts, you can’t run a PBM-style Medicaid formulary, feds say
As drug pricing moves at the federal level have floundered, state officials have taken matters into their own hands. But Massachusetts is discovering there’s a limit to drug-pricing innovation.
Last year, the state asked for permission to manage its Medicaid drug coverage using a formulary, just as private insurers and pharmacy benefits managers do. With the power to negotiate with drugmakers and trade discounts for coverage, Massachusetts could have sought better pricing.
But in a letter (PDF) to MassHealth assistant secretary Daniel Tsai, Center for Medicaid and CHIP Services Acting Director Tim Hill said the state’s proposal didn’t meet CMS requirements.
Massachusetts’ plan would have allowed the state to “continue to collect manufacturer rebates,” Hill wrote, while at the same time enabling it to exclude coverage on certain drugs. Under current laws, Medicaid programs are restricted from managing coverage and must pay for all drugs that are part of a rebate agreement between drugmakers and HHS.
CMS said it will continue to work with the state “on options to test innovative drug coverage mechanisms.” Arizona has also made a proposal to manage formulary coverage.
Massachusetts’ effort is one of dozens around the country as state officials aim to lower drug costs. The patchwork of new regulations is creating a growing problem for pharma, because companies increasingly must tweak their operations to meet differing reporting and transparency requirements in different states.
California, Nevada and Oregon are among the states to have passed drug pricing measures so far. According to the National Academy for State Health Policy, states around the country are considering bills focused on pharmacy benefit managers, price gouging and more.
Maryland passed its own legislation focused on “unconscionable” generic drug price hikes, but an appeals court found the state’s approach unconstitutional in April.
Meanwhile, the Trump Administration is pushing ahead with its own plan to lower drug costs. Unveiled in May, the plan seeks to step up negotiations and competition, provide incentives for lower list prices and help lower patients’ out-of-pocket costs. Already, the FDA is highlighting regulatory abuses that stifle generic competition.
President Trump in late May said some drugmakers were planning “major” drug price reductions, but so far no announcement has been made. Instead, to start July, Pfizer implemented 100 drug price hikes, according to the Financial Times. In a note Tuesday, Wells Fargo analyst David Maris outlined dozens of other price hikes from companies such as Depomed, Endo’s Par Pharmaceutical, Acorda Therapeutics, Roche and more.
Celgene pledges to limit price hikes—or does it?
Last October, as pharma companies ranging from Allergan to Sanofi were vowing to control price hikes, Celgene raised the prices of its cancer drugs Revlimid and Pomalyst so much that the cumulative increases on the products for 2017 were nearly double what its peers promised to avoid. Now, Celgene CEO Mark Alles seems to be bowing to the pressure to control prices, pledging that the company won’t increase the price of any product at rates higher that the projected rise in healthcare inflation.
But his pledge has a gaping loophole that raises questions about whether price-hike limits will apply to Revlimid—an $8-billion-a-year blood-cancer treatment that accounted for more than half of the company’s total revenues last year.
Alles said in a statement that the company will only raise the price of any drug in its portfolio once a year, and that any price hike will be “at a level no greater than the Centers for Medicare and Medicaid Services projected increase in National Health Expenditures for the year.” That rate for this year is 5.3%, he added.
But the next sentence could raise some eyebrows among drug-price watchdogs. “Because value is a guiding principle of our pricing decisions, there may be exceptional circumstances in which additional clinical or health economic evidence demonstrates a clear and significant increase in the value of one of our medicines where this standard would not apply.”
Does Revlimid’s standing as Celgene’s biggest blockbuster qualify it for “exceptional circumstances?” Alles didn’t say in his statement, and the company did not immediately respond to FiercePharma’s request for clarification.
Alles’ pledge comes amid close scrutiny from the federal government over pricing practices in Big Pharma. The industry is taking heat from the FDA, Health and Human Services Secretary Alex Azar, and of course, President Donald Trump himself, who claimed back in May that pharma companies were preparing to offer “massive drops” in pricing.
The FDA called out Celgene by name in May when it published a list online of complaints it has received from generic drugmakers seeking samples of branded products so they can develop their low-cost copycats. Celgene topped the list with 31 complaints, including 13 related to Revlimid.
The drug isn’t expected to lose its patent protection until 2027 in the U.S., though the company has had to fend off patent challenges to hold onto that exclusivity. Analysts project sales of the product will soar past $15 billion by 2020, and Celgene continues to test it in new indications and as part of combination therapies.
Revlimid’s potential expansion into new indications and combo cocktails could certainly qualify it for “exceptional circumstances,” depending on Celgene’s definition of that term. And there’s little doubt the company needs that product to continue to boost the top line while it works through some significant challenges.
Celgene’s problems started late last year, when it abandoned an experimental Crohn’s disease drug it had acquired for $710 million and slashed its revenue forecast for 2020 from $20 billion to $19 billion. Then the FDA slapped the company with a “refuse to file” verdict on its multiple sclerosis drug ozanimod, pushing a potential approval to 2019.
Celgene has reshuffled its management team, after saying goodbye to COO Scott Smith and business development chief George Golumbeski. Then, last month, Celgene named a replacement for retiring CFO Peter Kellogg, even though he’s not leaving until next year. David Elkins, a Johnson & Johnson veteran, started at Celgene on July 1 and will take over as CFO next month, with Elkins stepping into the position of chief corporate strategy officer until his retirement.
What role will pricing take in the turnaround strategy? That was a big topic of conversation after Celgene released its first-quarter earnings in April, and Alles could very well find himself fielding more questions about it on July 26, when the company releases its next quarterly report.
DEA Is Rescheduling Epidiolex, But Not (Yet) Cannabis Or CBD
The U.S. Food and Drug Administration (FDA) last week made history: By giving approval for U.K.-based GW Pharmaceuticals PLC-ADR GWPH 0.75% application to market Epidiolex (to medically treat severe forms of epilepsy), it marked the FDA’s groundbreaking admission that cannabis has medical value.
That said, despite some companies trying to leap into the fray of a perceived new CBD market, nothing else has (yet) changed. Cannabis and raw CBD remain federally illegal. For now, Epidiolex itself remains illegal for sale, pending the DEA’s scheduling decision (likely as Schedule IV), due by September 23.
“There is misunderstanding that cannabis or CBD will be immediately rescheduled, but that is not the case; itwill be Epidiolex itself. Yet the potential for marijuana or CBD is groundbreaking,” explained attorney Shawn Hauser, senior associate with Vicente Sederberg LLC, and director of the Denver-based law firm’s Hemp and Cannabinoid Group. “What is getting scheduled is the Epidiolex itself, pursuant to the new drug application, relating to its medical efficacy and low potential for abuse,” she said. “That will inform the federal law for the future. Marijuana is still a Schedule I substance; CBD is not scheduled itself, but as a substance derived from marijuana.”
The DEA has said that it has no plans to reschedule or deschedule cannabis per se, but that there is “discussion” about rescheduling CBD. Neither is likely to be changed with Epidiolex’s approval since individual drugs often receive their own schedule. Nevertheless, for the federal government to acknowledge the medical applications is huge.
Research scientists, doctors, and hospital administrators are governed by federal — not state — law, which has made the study of cannabis a risky, time-consuming endeavor. That’s now about to change, once the DEA schedules Epidiolex. Preliminary evidence suggests that CBD has use not just for epilepsy, but a whole host of neurological diseases, from Alzheimer’s and Parkinson’s, to multiple sclerosis, and some forms of brain cancers. Neuroscientists are anxious to examine the potential and parameters for cannabis’ medical applications; they will finally be at liberty to do their work.
“It will have a positive impact on the industry as a whole while providing patients with treatment for a severe form of epilepsy,” Hauser added. The approval also serves as a reminder that itis important for marijuana and hemp businessesnot to make unlawful drugclaims. Businesses should be aware that’s illegal and creates significant risk.”
As an FDA-approved pharmaceutical, Epidiolex can only be sold in licensed pharmacies, not dispensaries. Conversely, dispensaries are licensed by state agencies, and can only sell products authorized within a state program. Meanwhile, Epidiolex will likely be more expensive than CBD treatments within a state medical program, which typically cost $200 to $500 a month. But as an FDA-approved drug, Epidiolex can be covered by insurance, while state-authorized medical cannabis is not.
The dynamic begs the need for regulated standards. For a 2017 study published in the Journal of the American Medical Association, researchers tested 84 products purchased from 31 different online CBD sellers. About 70 percent of them had different levels of CBD than labeled, with nearly 50 percent having more CBD than indicated, and 25 percent having less. And 18 (or 21 percent) of the samples tested positive for THC, though not listed on the label.
“Hopefully we will see an expansion of research and other legitimatepharmaceutical medicines,” Hauser concluded. “There is a need for development of cannabis-based medicines, and forpatients to have access to cannabis as medicine. This could be a milestone that allows for more opportunities for research into cannabis; we as a country have been behind Israel and countries with fewer barriers on research into marijuana. I do not think that there will be any immediate avalanche effect on federal legislation, but I think it is generally positive for the industry to have a pharmaceutical lane for cannabis in addition to adult-use and nutraceutical lanes.”
TRIGR Therapeutics Licenses Oncology Asset from ABL Bio in $554.3M+ Deal
TRIGR Therapeutics, based in Irvine California, signed a deal with South Korean company ABL Bio Corporation. TIRGR is licensing the global commercial rights to ABL Bio’s pipeline of antibodies to treat cancer.
The antibodies include blood-brain barrier (BBB) penetrating bispecific antibodies, immune cell engaging bispecific antibodies, and a monoclonal antibody against an undisclosed target.
Under the terms of the deal, TRIGR will pay $4.3 million upfront to license global rights except for South Korea to five antibodies currently being developed by ABL Bio. ABL Bio is eligible or various milestone payments that could exceed $550 million, in addition to royalties. Also, TRIGR will share licensing revenue with ABL Bio in case it out-licenses any of the products to a third party.
“We are honored to be chosen as the partner of ABL Bio for their oncology pipeline,” said George Uy, TRIGR founder and chief executive officer, in a statement. “These assets include: a) BsAbs designed to cross the blood-brain barrier more efficiently combating brain tumors and b) immuno-modulating BsAbs engineered for dual engagement of the body’s immune cells (T cells and NK cells) against tumor-associated antigens in the tumor microenvironment. The antibodies truly represent the next wave in cancer immunotherapy.”
Uy went on to say, “It is TRIGR’s mission to identify and develop novel and paradigm-shifting immunotherapies. The delivery of antibodies into the brain, a privileged tissue in the human body and one of the last frontiers of drug delivery, to treat malignant gliomas and other brain cancers might enable TRIGR to bring new desperately-needed therapies to patients and their caregivers. Our new portfolio of unique immuno-modulatory BsAbs designed to activate patient T cells as well as NK cells in the tumor will allow TRIGR to establish itself as a leading biotechnology company. The BsAbs should also be valuable agents for combination therapies with cellular immunotherapies, such as CAR-T cell therapies and NK cell therapies.”
ABL Bio was founded in 2016, and since then has brought in $24.92 million in investments from Korea Investment Partners, DSC Investment and other institutional investors
Very little is known about TRIGR, although it is privately owned. It is focused on the Pacific Rim for clinical and commercial development, and is pulling together a management team based in the U.S. and China/Hong Kong as it activates its development programs with ABL Bio. It was founded by George Uy, a pharmaceutical sales executive who started with Roche, moved to Abraxis Oncology before it was acquired by Celgene, then was later senior vice president of Commercial Operations for Spectrum Pharmaceuticals. He was recently chief commercial officer of Sorrento Therapeutics. He is also currently chief executive officer of JUST C, maker of ARYA Curcumin+ line of health drinks and gummies. He also founded Hope Biosciences.
Pfizer Raises Prices of 40 Drugs, Some by Nearly 10%
In May President Donald Trump predicted a “massive drops” in drug prices following the signing of the Right-to-Try legislation, as well as a Health and Human Services initiative he called “the most sweeping action in history” to lower the cost of prescription drug prices.
The president’s predictions for lower drug prices fell on deaf ears at pharma giant Pfizer. The Wall Street Journal reported that the company increased the price of 40 of its most popularly-prescribed medications by nearly 10 percent. The Journal noted that some of the drugs that saw a price increase include cancer drug Xalkori (+ 9.4 percent), pain treatment Lyrica (+ 4 percent), cholesterol drug Lipitor (+ 9.4 percent), anti-smoking drug Chantix (+ 7 percent), depression drug Zoloft (+ 9.4 percent) and blood pressure medication Norvasc (+ 9.4 percent). This was the second time this year that Pfizer has increased the prices of some of its prescription medications, the Journal reported.
For the pharma companies, most argue that they do not profit much from the increase in prices due to the discounts and rebates offered to drug benefits managers.
In response to the Journal, Pfizer said many of its medications are sold at a discount. The company also noted that it is not responsible for “how much patients must bear in copays or other out-of-pocket costs,” the Journal said. For the majority of Pfizer medications, the company said its list price remains unchanged.
“We are modifying prices for about 10 percent of our medicines, including some instances where we’re decreasing the price,” the company told the Journal.
Pfizer wasn’t alone in its move to increase prices this week. The Journal also reported that Sanofi SA increased the costs of eczema drug Dupixent by 3 percent. Sanofi and its development partner Regeneron told the Journal that the 3 percent increase is the only planned increase for that medication this year.
In a noted to investors, Raymond James analyst Elliot Wilbur said that “Sub-6 percent inflation levels are here to stay,” the Journal said.
The price of prescription medications has been a political hot-button for several years. Prior to being sworn in as president, Trump said that pharmaceutical companies are “getting away with murder” when it comes to the prices the companies charge for medication.
With the outcry, many drugmakers have pledged to only address potential price increases once per year. Last year Merck pulled back the curtain on its pricing practices in the United States by publishing a “Pricing Action Transparency Report” for 2016. In its disclosure, Merck noted that the pricing takes into account rebates, discounts and returns. Allergan’s Chief Executive Officer Brent Saunders publicly vowed to keep price increases on the company’s drugs under 10 percent in 2017. Last month Celgene Chief Executive Officer Mark Alles posted a note on the company website that set fort its approach to price increases. Alles said any increase posted by Celgene “will be limited to no more than once a year and at a level no greater than the Centers for Medicare and Medicaid Services projected an increase in National Health Expenditures for the year.” For 2018, that rate is 5.3 percent, Alles wrote. However, Alles also noted that there could be “exceptional circumstances” that might force the company to increase a price beyond that threshold.
In a separate article, the Journal noted that July is a popular month for pharmaceutical companies to quietly raise the prices of their medications. It’s something that the Trump administration is apparently paying some attention to. HHS Secretary Alex Azar told a congressional panel last week that he hopes companies will “practice restraint” when it comes to increasing the prices of prescription drugs, the Journal reported.
Novartis Walks Away from 2015 Aveo’s Antibody Agreement
Shares of AVEO Oncology are falling this morning after the company revealed Novartis has walked away from its development deal for the company’s proprietary antibody AV-380, as well as other antibodies that inhibit Growth Differentiation Factor 15.
Novartis initially struck the licensing agreement with Aveo in 2015. The deal was worth an estimated $326 million, which included $15 million in upfront payments and $311 million in milestones. At the time the initial deal was announced Aveo’s AV-380 asset was seen as a potentially promising treatment for cachexia secondary to multiple disease states, including cancer, chronic kidney disease, congestive heart failure and chronic obstructive pulmonary disease.
That promising treatment though has not gone as far, or as rapidly, as Aveo likely hoped. Cambridge, Mass.-based Aveo quietly announced the end of the AV-380 agreement in a filing with the U.S. Securities and Exchange Commission this week. According to the filing, Novartis announced its termination one day after Aveo reached out to the Swiss company regarding the slow development of the asset. Aveo said it provided Novartis with a notice that disputed Novartis’ compliance with the obligations laid out in the 2015 licensing agreement.
One day after Aveo reached out, Novartis announced it was discontinuing the program and returning the asset to Aveo. In the filing, Aveo said that Novartis said the AV-380 Program is an important asset, however, developmental delays and a shift in management and strategic priorities at the Swiss pharma company resulted in the termination of the agreement. The termination is expected to be finalized on Aug. 28, 60 days after Novartis announced the termination of the development agreement.
Aveo said it hopes to settle matters at the managerial level, but if dispute resolution procedures cannot be resolved there, then it will likely seek arbitration. The dispute resolutions could run parallel to the termination process, Aveo said.
Aveo said that Novartis’ decision to terminate the AV-380 program is without cause and triggers the termination of all licenses and other rights granted by Aveo to Novartis with regard to the AV-380 program. Additionally, the agreement calls for Novartis to transfer all preclinical, technical, manufacturing and other data to Aveo.
While Novartis will return the asset, Aveo said in the filing that Novartis has not included any of the potential milestone or other potential payments under that $311 million licensing agreement. That loss of income will not impact Aveo’s cash guidance, the company said in its filing. It has however caused some investors to balk at the stock this morning, causing the price to dip in morning trading.
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