Corrupted data on gene therapy approved to treat babies

The exposure of medical fraud is not new. In the past, drugs have been brought to market before clinical trials revealed a deadly list of side effects, including heart attacks and deaths, as in the case of Vioxx.¹ ProCon.org published a list in 2014 of 35 drugs pulled from the market after research revealed they caused more damage than benefit to users.²

You need only take a cursory glance at the epidemic that opioid manufacturers have caused in their search for profit, sometimes boasting they could become an “end-to-end” provider by supplying both the addictive drug and the cure for the addiction.³

In 2015 Dr. Anil Potti from Duke University was found guilty of research misconduct,⁴ and Duke faced lawsuits filed by patients in his clinical trials.⁵ Potti’s research was first heralded as a groundbreaking game changer, but is now an example of how fraud can occur anywhere.

Had Duke University paid attention to reports from a medical student in 2008, they could have avoided the ensuing public and political challenges. Instead, Potti’s protectors pressured the student to be silent, in a move to protect their own interests.⁶

Recently, it was revealed that scientists at Novartis hid manipulated data from animal studies while seeking approval from the FDA for a gene therapy drug meant to treat babies with an inherited disease, spinal muscular atrophy.⁷

Big Pharma corrupts data but keeps profits

AveXis, a subsidiary of Novartis, is aimed at developing and commercializing gene therapy.⁸ May 24, 2019, the company received approval to release Zolgensma, which was considered a major milestone. However, it is also the most expensive treatment ever offered on the market, at a whopping price of $2.1 million for a single dose.^9,10

AveXis knew of the data manipulation in March,¹¹ a full two months before the drug was officially approved by the FDA. Dr. Wilson Bryon, director of the FDA division reviewing the drug, commented to STAT¹² that had the agency been told of the data manipulation, approval of the drug would have been delayed.

In what appears to be an opposing statement, Dr. Peters Marks, director of the FDA’s Center for Biologics Evaluation and Research,¹³ was quoted in a press release saying,¹⁴ “The FDA is carefully assessing this situation and remains confident that Zolgensma should remain on the market.” In the same statement Marks also said,¹⁵ “The agency will use its full authorities to take action, if appropriate, which may include civil or criminal penalties.”

In a letter to Ned Sharpless, acting head of the FDA, five senators wrote,¹⁶ "This scandal smacks of the pharmaceutical industry's privilege and greed, and Americans are sick of it.” The senators urged the FDA to take action:¹⁷

" … to use your full authorities to hold AveXis accountable for its malfeasance. Anything short of a forceful response would signal a green light to future pharmaceutical misbehavior."

Business Insider¹⁸ reports Novartis declined to comment on the content of the letter from the senators. In a Twitter conversation¹⁹ between Dr. Peter Bach²⁰ of Memorial Sloan Kettering Cancer Center and past FDA Commissioner, Dr. Scott Gottlieb,^21,22 the problem was clearly acknowledged:

Bach: “I don’t know the rules in detail, but presumably Nvs could have told the FDA to pause its review to ensure the approval was not based on data suspected to be (or known to be) fabricated. This whole thing has the ‘wrongs were committed but there were no wrongdoers’ feel.”

Gottlieb: “Based on the tone and substance of the FDA statement today, Peter, I suspect there will be wrongdoers here. And consequences.”

Drugmakers not required to report suspected data corruption

In their letter to Sharpless, the five senators described how taxpayers had funded benefits to Novartis in order to speed the regulatory and approval processes for their new drug. They wrote:²³

“What makes this unscrupulous action even more appalling is the fact that AveXis was the beneficiary of numerous federal taxpayer-funded benefits and incentives, including obtaining Fast Track, Breakthrough Therapy, and Priority Review designations — ensuring that Zolgensma would be sped through the regulatory approval process. All the while, AveXis breaks records, and budgets, with its staggering $2.1 million price.”

In the same letter, the senators requested that the FDA answer questions about how it plans to deal with cases of data manipulation from drug companies. Additionally, they wanted an explanation about why the FDA had decided to drop a regulation requiring pharmaceutical companies to report any suspected data manipulation.²⁴

Dr. Vasant Narasimhan became the chief executive officer of Novartis on February 1, 2018.²⁵ Narasimhan defended the company's decision to delay release of the information about manipulated data and said the company “thoroughly, aggressively”²⁶ investigated the issue.

The New York Times²⁷ reports that when Narasimhan assumed this role, his mission was to restore the reputation of Novartis following several allegations of price-fixing, past data manipulation and the decision to hire Michael Cohen, President Trump’s ex-lawyer who pleaded guilty to making false statements to Congress.²⁸

Narasimhan said they waited before releasing information about data manipulation in order to perform their own internal investigation and not in an effort to hasten the approval process.²⁹ Novartis continues to assert the falsified data were limited to the early phases of research involving animals; this was discontinued in the summer of 2018.

Insurance companies picking up $2.1 million bill

While Zolgensma is the second gene therapy drug to be approved by the FDA, the government agency expects to be approving between 10 and 20 cell and gene therapy products each year by 2025.³⁰ Zolgensma is a $2.1 million one-time drug for the treatment of spinal muscular atrophy in children under 2.

Spinal muscular atrophy is a muscle wasting disease, affecting about 400 children each year. In the most severe form, children die before age 2. At one point, UnitedHealthcare refused payment for several cases. Later, they reversed their decision after pressure from families and intense media coverage.³¹

The FDA released an inspection report from the mice used in the early phases of the research and found how long the mice lived was different from the actual value in some cases. While the FDA reported the data were manipulated, they would not say if they believed the information was deliberately falsified.³²

Novartis concerned regulations may impact business

The high cost of prescriptions has become a political issue, with most calling for change. Bausch Health, possibly best known for their eye care products, is led by CEO Joseph Papa. In an interview with CNBC, Papa said pharmaceuticals are the most cost-effective way to treat and improve health care.³³

Also under the Bausch Health umbrella is a dermatology business, Ortho Dermatologics, which received approval in early 2019 for a lotion to treat psoriasis. In two clinical trials, the drugmaker posted a success rate of 36% in the first study and 45% in the second.

Despite pledges from Congress to help regulate prescription prices, Papa remains unconcerned.³⁴ However, Novartis is not quite as unruffled by movements in Congress toward greater regulation.

The company is standing behind their newest gene therapy drug, and defends the massive price tag that nearly all families would find impossible to pay without full coverage insurance. At the same time, Novartis’ annual report cites concern for transparency in the way their company may be forced to do business:³⁵

“For example, we are faced with increasing pressures, including new laws and regulations from around the world, to be more transparent with respect to how we do business, including with respect to our interactions with healthcare professionals and organizations.

These laws and regulations include requirements that we disclose payments or other transfers of value made to healthcare professionals and organizations, as well as information relating to the prices for our products. Such measures, including any additional such measures that may be put in place, could have a material adverse impact on our business, financial condition, or results of operations.”

Novartis dumped vaccine program and more

Novartis’s headquarters are in Switzerland and the company has offices in multiple countries.³⁶ If their name sounds familiar it might be from years of manufacturing and supplying vaccines, including flu vaccines and those for meningitis B. Their vaccine division was formed in 2006 but began posting losses in 2013.³⁷

In 2015, Novartis sold the flu vaccine business for $275 million to Australia's CSL. This placed CSL as the world's second largest flu vaccine supplier.³⁸ The acquisition also included the cell-based manufacturing facility in North Carolina.

This was a win for CSL as it was the first of its kind in the U.S. The cost of $487 million was in part paid by the U.S. Department of Health and Human Services. This was a part of the organization’s pandemic preparedness efforts.³⁹ In other words, U.S. taxpayers funded the facility, which was later sold to Australia.

GlaxoSmithKline acquired the remaining vaccine business from Novartis in 2015 for $7.1 billion, which included nearly 20 vaccines the company had in development.⁴⁰ In addition, GSK divested its oncology portfolio to Novartis for cash consideration of $16 billion.⁴¹

Novartis began their companywide restructure with the divestment of their vaccine portfolio, over-the-counter drugs and animal health sections.⁴² In another deal closed December 2015, Novartis sold Kayersberg Pharmaceuticals from their Alcon unit in a bid to improve financial margins and focus their attention in a different direction.⁴³

By June 2018, Novartis had announced the sale of the entire Alcon eye-care unit⁴⁴ as Narasimhan continued to focus the attention of the company on prescription drugs. In 2018, Novartis bought AveXis for $8.7 billion to acquire the then experimental Zolgensma.⁴⁵

As the pharmaceutical industry jockeys for position in an ever-changing political environment, it is the consumer who ultimately loses the battle. Although Papa believes pharmaceutical treatments are the answer to health and wellness, it has been my assertion for decades your life choices have a significant effect on your health, including nutrition, sleep, hydration and exercise.