Gilead loses key patent claims for Sovaldi in China, opening door to earlier generic

A partial patent invalidation by Chinese authorities has shaken the case Gilead has been building for its hep C star Sovaldi by removing a key barrier to generic entry.

The decision means knockoffs of the highly effective hep C treatment can arrive as early as next year — rather than 2024, when the patent was originally set to expire — according to the Initiative for Medicines, Access, and Knowledge, or I-MAK. I-MAK filed one of the two requests for patent invalidation cited in the ruling, together with Chinese drugmaker Fujian Cosunter Pharma.

Because the patent concerns sofosbuvir, a crucial base compound that’s also used to make combo drugs like Harvoni and Epclusa, this decision could affect not just one product but Gilead’s whole hep C franchise in the country.

In response to my question as to whether Gilead will appeal the ruling (they have three months to do so), a spokesperson says the Foster City, CA-based company has not withdrawn their claims to the sofosbuvir compound patent application in China. Here’s the rest of the response:

This patent application is currently being reviewed by the Patent Review Board (PRB). Last week China’s PRB confirmed the validity of claims covering the SOF metabolites. This decision has no impact on our SOF compound patent application. Gilead is confident in the intellectual property covering the sofosbuvir compound and all its hepatitis C medicines, which bring the potential of a cure to the vast majority of patients suffering from chronic hepatitis C virus (HCV) infection. In the meantime, we will continue to work with the Chinese government to facilitate broad access to Gilead’s hepatitis C medicines.

While Sovaldi was launched in China at one-fifth the contemporary price in the US — almost $9,000 for a 12-week regime — its price still frequently comes under attack, as it has in many other countries around the world. In fact, Gilead has drawn criticism ever since it began selling the drug at $84,000 in the US. And whereas Gilead designed licensing deals with generic companies in countries like Ukraine, Belarus, Thailand and Malaysia in response to complaints, no such agreement was struck in China.

Back in 2015, two years before Sovaldi would be approved in China, the authorities had rejected Gilead’s application for an inactive prodrug that is metabolized once in the body.

I-MAK, which also played a role in that decision, has been bringing legal challenges against Gilead in a number of other countries, including the US. Its co-founder Tahir Amin told STAT that even though Gilead still holds four remaining patent claims on Sovaldi and data exclusivity in China, they shouldn’t hinder generic makers as much as this patent had.

Cosunter, which marketed China’s first hep B generic, is said to be developing a copycat version of Sovaldi.

https://bit.ly/2MpdrK8

Exodus of top Gilead execs continues as newly named CMO Cheng exits

The exodus of top execs out of a high-performing Gilead is continuing Tuesday evening.

The biotech, which has been the most productive drug developer over the past 5 years, noted Tuesday night that Chief Medical Officer Andre Cheng is leaving the company “to pursue another opportunity.”

As of now, we don’t know what that other opportunity is, but Gilead $GILD has recently seen the departure of chief R&D exec Norbert Bischofberger (to a startup) as well as the announced exits of CEO John Milligan and longtime company exec John Martin, executive chairman.

Cheng plans to stay on to September 7 to help with the transition, according to Gilead. Meanwhile Gregg Alton has been appointed to the newly created position of chief patient officer while Diana Brainard was promoted to Senior Vice President, HIV and Emerging Viral Infections.

Cheng joined Gilead 19 years ago to lead the company’s development-stage programs in HIV/AIDS. He was named Executive Vice President in 2015 and Chief Medical Officer in March.

As we reported recently, Gilead has had the best record over the past 5 years in advancing new blockbusters to the market, even after the phenomenal rise and fall of its hep C franchise, where the company provided a painless cure for the disease, and then watched the franchise melt away. Gilead remains the leader in HIV drug development, where finding simpler combination therapies remains the primary task in the field.

https://bit.ly/2KXf3G6

Piper not worried by trajectory of Optinose’s Xhance, stays Overweight

Piper Jaffray analyst David Amsellem says he’s not worried about the growth trajectory of Optinose’s Xhance with the stock down 31% following this morning’s earnings report. There is understandably some concern that the company’s focus on more aggressive co-pay assistance may hurt the drug’s average selling price and the growth, Amsellem tells investors in an intraday research note. The analyst, however, views Optinose’s transition away from the Xhance sampling program as positive and he expects the company to continue to execute on payer contracts. He lowered his price target for the shares to $30 from $34 and keeps an Overweight rating on Optinose.

https://bit.ly/2Mntyrv

GW Pharmaceuticals initiated at Stifel

GW Pharmaceuticals initiated with a Buy at Stifel. Stifel analyst Paul Matteis started GW Pharmaceuticals with a Buy rating and $181 price target. The analyst expects a “strong” Epidiolex launch in Dravet/Lennox Gastaut with use in refractory pediatric epilepsy and put an 80% odds-of-success for Epidiolex in Tuberous Sclerosis complex. The latter could de-risk another $250M in on-label sales, Matteis tells investors in a research note. The analyst’s epilepsy physician survey suggests broad physician and patient awareness of Epidiolex ahead of the launch and he believes the 2019 consensus sales estimate of $115M “seems doable.” His believes Epidiolex will hit $1.5B in U.S. sales in 2023.

https://bit.ly/2MhAx6k

Actinium Pharmaceuticals to hold a conference call

Conference call to provide an update on the Pivotal Phase 3 SIERRA Trial (Study of Iomab-B in Elderly Relapsed/Refractory AML) of Iomab-B will be held on August 15 at 9 am. Weblink: https://onecast.thinkpragmatic.com/ses/HKwlrC68IHB_UiNbwrpb4w~~

https://bit.ly/2MemKx6

Threatened by Cyber Attacks, Pharma Invests in Security Measures

Western government agencies have been warning of an increase in cyber espionage from nefarious black hats and governments for years. The targets have typically been government and financial installations. But a new warning suggests that biotechnology could be a key target for cyber hackers.

Recently, the federal National Counterintelligence and Security Center (NCSC) pegged biotechnology as a rich target for foreign hackers. A Chemistry World article noted that the government report points to the biopharmaceutical industry in particular as a potential target. Chemistry World reported that “biomaterials, biopharmaceuticals and new vaccines and drugs as of particular interest” to foreign hackers. Additionally, the government report said hackers are interested in garnering information on advanced medical devices, infectious disease treatment and genetically modified organisms.

“The United States remains a global center for research, development, and innovation across multiple high-technology sectors. Federal research institutions, universities, and corporations are regularly targeted by online actors seeking all manner of proprietary information and the overall long-term trend remains worrisome,” the NCSC report said.

The threat is not a new one. The pharmaceutical industry has already been hit with multiple cyber-attacks. Last year, pharma giant Merck was the target of an attack. In June 2017, Merck & Co., among other companies, was targeted by a malware attack that was believed to have originated in Ukraine. The malware strain, known as NotPetya, is a type of ransomware, and it shut down computer systems and sought to extort funds from companies in order to release those compromised systems.

When Merck was hit by the malware, the company said the event forced it to halt production, which hurt profits. It was enough to prompt federal lawmakers to take action after they feared drug shortages.

Cyber attacks, particularly ransomware attacks, are expected to be on the rise in the next few years. Earlier this summer, Kaspersky Lab’s APT trends report for 2017 pointed to hackers targeting corporate interests, including energy companies, TechRepublic reported.

Since the Merck attack, the threat of cyber warfare against the pharma industry has not waned. In March, Security Week highlighted a number of attacks on pharma and healthcare groups over the past year. The report noted that a U.S. clinic was attacked and data information from a Phase II trial was stolen. The report did not name the clinic, nor did it name the company or companies that were involved with the trial. Security Week noted that the same cyber bandit may have also been responsible for a similar attack on a U.K.-based facility that experienced a data breach of Phase II information.

The attacks on Merck and the other healthcare facilities highlights a need for companies to place a premium on data security. And that’s something that pharma companies appear to be making investments in, Pharmaceutical-Technology reported. Citing a GlobalData survey, PTreported that 79 percent of pharmaceutical companies are making investments in identity & access management (IAM) solutions. These investments are driven by the “need to manage electronic user identities and ensure data privacy while avoiding any misuse of critical business information.”

The same survey shows that pharma companies are also investing in data backup and archiving services to protect their proprietary information.

https://bit.ly/2Mt2NSD

Gene Therapy May Stop Hemophilia, But With Some Long-Term Concerns

Gene therapy has been a dream for many researchers for decades—inserting a healthier gene into patients’ cells to replace defective genes and curing diseases. Not all diseases are good candidates for it, and it’s only in the last decade or so that the technology has been advanced enough for gene therapy to be a real possibility. Only a few gene therapies have been approvedso far, such as Spark Therapeutics’ Luxturna (voretigene neparvovec) for a rare, genetic form of blindness called retinal dystrophy.

One disease that would seem to be a good target for gene therapy is hemophilia. People with hemophilia have difficulty or an inability in forming blood clots. This puts them at high risk of uncontrolled bleeding into a muscle or joint, or internal bleeding or uncontrolled bleeding from injury, even minor injuries. Treatments involve injections of clotting proteins, but they are expensive, costing as much as $1 million per year. It is estimated that annual medical bills related to hospitalizations and surgeries hit $1 million per year, with $250,000 to $300,000 and up for the clotting proteins.

Several companies appear to be making progress for gene therapy for hemophilia. Spark is one and BioMarin Pharmaceuticals is another. Both gene therapies use a virus known as adeno-associated virus (AAV), which is the most common virus used as a vector in gene therapy. It poses at least two problems. First, it isn’t large enough to carry many full genes, for example, the genes related to missing clotting factor VIII or factor IX, or the dystrophin gene that is damaged in Duchenne muscular dystrophy (DMD). As a result, scientists have developed truncated versions of the genes that still work. The second problem is that, because the vector is a virus, the immune system may react to it. And the higher the dose required to be effective, the more likely there is to be an immune reaction.

To date, gene therapies for hemophilia, which affects mostly men, are showing promise. But one concern is that they don’t necessarily seem to be permanently effective, although the jury is still out on that. Steven Pipe, director of the hemophilia and coagulation disorders program at the University of Michigan and lead investigator of one of BioMarin’s clinical trials, told The New York Times, “we are anticipating that this is a once-in-a-lifetime treatment.”

Patients with hemophilia A have a mutation in the gene for factor VIII. Patients with hemophilia B have a mutation in the gene for clotting factor IX. Both diseases are essentially the same, although hemophilia A is more common. Spark’s gene therapy focuses on hemophilia B. BioMarin’s focuses on hemophilia A. Pfizer has taken over Spark’s hemophilia B work.

On May 22, Pfizer and Spark announced a follow-up of more than 15 participants in the Phase I/II clinical trial of SPK-9001 for hemophilia B. All 15 patients had discontinued routine infusions of factor IX concentrates and none experienced serious adverse events. On July 16, they announced the launch of a Phase III trial of SPK-9001, which is now named fidanacogene elaparvovec.

Also on May 22, BioMarin released updated data from its Phase I/II trial of valoctocogene roxaparvovec (BMN 270) for hemophilia A. It too showed continued and substantial reductions in bleeding requiring factor VIII infusions, no spontaneous bleeds and elimination of bleeds in target joints in the second year.

The New York Times writes, “Results from the two companies’ preliminary trials were not perfect. Patients in BioMarin’s hemophilia A trial got, on average, normal or above normal levels of factor VIII in their blood, but in the second year, those levels dropped to a median of 46 percent. It’s not clear why.”

The Times goes on to write, “Patients in Spark’s hemophilia B trial only reached on average 35 percent of normal blood levels of factor IX. But those levels have remained steady for the two years they have been followed.”

Which, as it turns out, is good enough for blood to clot. All of which sounds and seems miraculous for patients with hemophilia. And if the results hold for these patients, it probably will be a miracle.

https://bit.ly/2P8KK2A