Thermo Fisher to manufacture gene therapies being developed by Amicus

Amicus Therapeutics has already forked over $100 million for 10 gene therapies. It is building a new R&D operation to advance them. But when it comes to manufacturing, it is turning to a CDMO.

The New Jersey-based biotech today announced it has an arrangement with Thermo Fisher Scientific’s gene therapy unit to provide clinical supply and commercial production of its gene therapies to cure intrathecal AAV Batten diseases, as it works to get them to the market.

“As we advance one of the industry’s leading gene therapy pipelines, our partnership with Brammer Bio, now part of Thermo Fisher, is a significant next step in fulfilling our manufacturing strategy so that we can deliver novel gene therapies to more people living with rare genetic diseases as quickly as possible, especially in devastating diseases like Batten’s, where time is of the essence,” Amicus CEO John F. Crowley, said in a statement.

He said the company will “embed” its team and strategic partners in the tech transfer process to Thermo Fisher.

New Jersey’s Amicus has been working on drugs to stabilize lysosomal storage disorders (LSDs) like Fabry disease and Pompe disease for a few years. Last year it nabbed FDA approval last for Galafold to treat Fabry disease. But with the $100 million deal with Celenex, it has a chance to cure the rare conditions.

Celenex has been working on gene therapies for lysosomal disorder Batten disease. Among the programs Amicus bought are gene therapies that target the CLN6 and CLN3 forms of Batten.

Earlier this year, Amicus said it will build a 75,000-square-foot facility in Philadelphia to serve as the global headquarters for Amicus’ scientific work and the home of its gene therapy leadership team.

Thermo Fisher is new to gene therapies as well. The company earlier this year ponied up $1.7 billion to nab viral vector producer Brammer Bio, giving it entry into the field. It acquired manufacturing locations in Cambridge, Massachusetts and Florida, along with 600 employees in the deal.

https://www.fiercepharma.com/manufacturing/thermo-fisher-to-manufacture-gene-therapies-being-developed-by-amicus

Array played Pfizer’s eagerness to land a deal on time—and got itself a better offer

When it comes to buying an experienced cancer drug specialist, a bidding war is naturally expected. But in the case of Pfizer’s $11 billion deal for Array BioPharma, that didn’t happen. Still, it didn’t stop the two companies from pressing each other.

Pfizer was the only one who’d ever made an offer for Array, even though two other firms also expressed interest, Array disclosed in a recent securities filing. That makes the deal the second recent one in the targeted cancer realm that took shape without much drama—Eli Lilly’s $8 billion buyout of Loxo Oncology didn’t emerge from a bidding war, either.

Despite the absence of competition, Array investors shouldn’t worry, as the documents suggest that “Pfizer was proactively willing to pay a substantial premium that exceeded Array’s threshold,” SVB Leerink analysts said in a Monday note to clients, adopting the same tone they had for Lilly-Loxo a few months ago.

In January 2017, Array hired Centerview Partners to advise it in a possible strategic transaction. However, of the four parties Centerview contacted, including Pfizer, none came forward with a proposal of any kind—partnership or acquisition.

Almost two years later, in October 2018, the CEO of a multinational biopharma company approached Array’s CEO Ron Squarer about a potential merger. But after running an internal review, the Array board decided not to sell the company at that time. During the meeting, the board formed a new committee that excluded one director, who had a relationship with that potential buyer, Party A.

Party A’s CEO reassured Squarer of the company’s interest in a transaction twice in the following November and January, only short of offering any financial terms.

In the meantime, another company, Party B, showed some interest in making a deal with Array. The two signed a confidentiality agreement for a potential research team-up and amended it in May to allow for M&A-related discussions.

Things also turned cozy with Pfizer. In February, Array’s Chief Operating Officer, Andrew Robbins, visited Pfizer’s offices in New York City. He met with the Big Pharma’s business development executives to discuss Array’s commercialization of MEK-BRAF combo inhibitor Mektovi and Braftovi, as well as its research platform. In exchange, Pfizer’s management visited Array’s headquarters in Boulder, Colorado in May.

Array and Pfizer had held talks even before 2017, which in some cases involved “exchanging confidential information,” according to the Array document.

One data set likely helped make up Pfizer’s mind to make a formal move. Array unveiled interim results from the phase 3 Beacon trial, showing a combination of Array’s Braftovi, Mektovi and the anti-EGFR drug Erbitux could significantly extend lives in certain patients with metastatic colorectal cancer. SVB Leerink analysts at that time called the data “extremely compelling,” as it marked the first randomized, controlled trial to show an overall survival benefit in the patient population.

A week after the positive results, Array’s Robbins and Chief Scientific Officer Nicholas Saccomano met with an expanded, C-Suite-level team of Pfizer executives to discuss a deal.

The next day, on May 29, Pfizer CEO Albert Bourla reached out to Squarer, offering to buy Array at $44 per share, which represented a 62% premium to Array’s previous closing price. Pfizer sounded eager, making clear that it would like to publicize the deal on June 17.

But Array didn’t take Pfizer up on its first offer. Array’s special committee decided that the $44-apiece offer “was insufficient to allow Pfizer access to additional diligence or for Array to commit to Pfizer’s timeline of a June 17 announcement,” the company described in the filing. Capitalizing on Pfizer’s keenness to close a deal, however, Array’s board said it would be interested on that date if Pfizer came up with a higher price.

Pfizer quickly responded, upping its offer to $48 per share. But it also provided Array little time for additional back-and-forth, linking that proposal with the target June 17 date. That meant just two weeks for Array to decide, refine the merger agreement and execute.

Meanwhile, Array’s discussions with Party B didn’t go anywhere, despite a meeting between Array’s advisers and representatives of Party B in Chicago during this year’s American Society of Clinical Oncology annual meeting, plus two conference calls afterward to discuss Array’s programs.

On June 11, as its last try, Centerview told Party B that Array had already made meaningful progress toward a transaction. Party B said “it would not likely be in a position to submit a formal proposal to acquire Array in the near term” and also suggested that it wouldn’t be able to offer an attractive price, according to the Array document.

At that, Array decided to accept Pfizer’s $48-per-share offer on June 14, a Friday. And the two unveiled the deal on June 17.

The Array disclosure also provided a glimpse into the company’s internal financial forecasts for the years to come. As of June 14, the company expected its total revenue could reach $452 million in 2020, growing all the way to $2.57 billion in 2031.

https://www.fiercepharma.com/pharma/array-played-pfizer-s-eagerness-to-land-a-deal-time-and-got-itself-a-better-offer

Roche closes on EU approval for Tecentriq in breast cancer

Roche is heading for EU approval of Tecentriq as first-line therapy for triple-negative breast cancer (TNBC), ahead of its checkpoint inhibitor rivals.

The Committee for Medicinal Products for Human Use (CHMP) backed the use of the PD-L1 inhibitor in patients with locally-advanced or metastatic TNBC that cannot be treated with surgery and who haven’t previously received chemotherapy. The EMA typically approves drugs a few weeks after a positive CHMP opinion.

The new indication – which was approved by the FDA in March – is seen as a big commercial opportunity for Tecentriq (atezolizumab) as it is the first checkpoint inhibitor to be cleared for use in any form of breast cancer.

It not only represents a sizeable patient population, affecting around 15% of the 2 million women diagnosed with breast cancer each year worldwide, but also has no competition yet from other cancer immunotherapies such as Merck & Co/MSD’s market leading Keytruda and Bristol-Myers Squibb’s Opdivo.

The CHMP positive opinion applies to women whose tumours express PD-L1 but lack receptors for oestrogen, progesterone or HER2 – effectively preventing treatment with hormonal therapies or anti-HER2 drugs like Roche’s Herceptin.

TNBC is a particularly aggressive form of breast cancer with treatment options that until recently were mostly limited to surgery, radiotherapy and chemotherapy, depending on the stage of the disease. AstraZeneca’s Lynparza and Pfizer’s Lynparza can be used in TNBC, but only in patients whose cancers express the BRCA biomarker.

Five-year survival rates tend to be much lower with TNBC than with other breast cancer types, so Tecentriq is a welcome new addition to the treatment options for this form of the disease.

Analysts have also suggested that Roche has a lead of at least a year over other checkpoint inhibitors in TNBC, with Keytruda considered to be closest behind with phase 3 results due later this year.

The EU positive opinion is for Tecentriq in combination with Celgene’s chemotherapy drug Abraxane (nab-paclitaxel) and is based on the results of the IMpassion130 trial, which showed adding Tecentriq to Abraxane reduced the risk of progression or death by 38% compared with Abraxane alone in this patient population.

Tecentriq is already approved to treat bladder cancer and non-small cell lung cancer (NSCLC), and the new indication is expected to help accelerate growth for the product, which made around $766 million in sales last year.

Roche has suggested in the past that breast cancer could eventually add another $500 million to $1 billion in revenues for the drug as it chases after Keytruda and Opdivo, which are predicted to top $9 billion and $7 billion in sales respectively this year.

To try to maintain its lead in TNBC the company has no fewer than seven phase 3 trials ongoing, including studies in patients with early and advanced stages of the disease.

Roche closes on EU approval for Tecentriq in breast cancer

CHMP says no to Amgen’s osteoporosis drug Evenity

Amgen and UCB have suffered another setback as they try to build momentum for Evenity, their new antibody therapy for osteoporosis.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) has decided it cannot approve Evenity (romosozumab), issuing a negative opinion on the drug for the treatment of severe osteoporosis in postmenopausal women who are at risk of fracture.

It’s a blow to Amgen and Belgian partner UCB, who have been battling to get Evenity approved and onto the market for several years in order to provide a replacement to Amgen’s blockbuster osteoporosis Prolia/Xgeva (denosumab).

Prolia, a RANK inhibitor, is one of Amgen’s top-selling drugs with sales of $2.3 billion last year, but will start losing patent protection in Europe in 2022 and in the US in 2025.

In April, the duo made a big breakthrough for Evenity when the US FDA approved the drug, having previously rejected it in 2017 on safety grounds. They also picked up a Japanese approval around the same time, but hopes that they could quickly add an EU license to Evenity’s tally have now been dashed.

Evenity was approved by the US regulator with a boxed warning that it may increase the risk of heart attack, stroke and cardiovascular death – a safety issue that was responsible for the FDA’s earlier rejection of the drug and also led to the CHMP’s negative opinion.

In its assessment, the advisory committee said “as it was unclear why the medicine appeared to increase the risk of heart and circulatory problems, and there was no obvious group of patients in whom the risk of these was lower, measures to reduce the risk could not readily be put in place.”

The CHMP was also not convinced about the efficacy of the drug in patients with less severe osteoporosis, saying the “benefit was not so convincing” in this group.

The companies say they are planning to submit a written notice to the regulatory agency, requesting a re-evaluation of Evenity for the given indication.

The new drug works in a different way to Prolia, blocking the effects of the protein sclerostin and as a consequence building new bone formation. However it has been approved with a narrower indication than Amgen’s older drug, aimed at high-risk rather than all postmenopausal osteoporosis patients.

It also works differently to other widely-prescribed drugs, including bisphosphonates like Merck & Co/MSD’s Fosamax (alendronate) which work only by blocking bone destruction. Evenity topped alendronate in a head-to-head trial when it came to cutting fracture rates.

CHMP says no to Amgen’s osteoporosis drug Evenity

AstraZeneca’s asthma, diabetes drugs get label boosts in EU

Two of AstraZeneca’s most important drugs have received a boost, after European regulators backed a pen allowing people to inject themselves with respiratory drug Fasenra, and agreed that cardiovascular benefits data could be added to the label of diabetes drug Forxiga.

The European Medicines Agency’s CHMP regulatory committee gave a positive opinion to add a self-administration option for asthma injection Fasenra (benralizumab), based on a new delivery method as a pre-filled, single-use auto-injector.

Fasenra already has a convenience advantage over two rivals from the same class, GlaxoSmithKline’s Nucala (mepolizumab) and Teva’s rival Cinqaero (reslizumab) as it is given every eight weeks, after the first three doses administered that are four weeks apart.

Both Nucala and Cinqaero, which are also interleukin-5 inhibitors, are injected every four weeks.

Following the CHMP’s nod, the drug’s label can be changed without need for confirmation from the European Commission.

AstraZeneca expects a regulatory decision by the FDA on self-administration and the new pre-filled, single-use auto-injector device in the second half of 2019.

Fasenra is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries.

However, in May last year AZ said Fasenra had failed in a phase 3 trial in chronic obstructive pulmonary disease (COPD), saying it did not provide a statistically significant reduction in exacerbations, a blow to its development in this other indication. NICE has also restricted its funding for NHS patients.

The positive opinion for self-administration and the Fasenra pen is supported by the phase 3 GREGALE and GRECO trials, and the phase 1 AMES trial, respectively. The safety and tolerability of Fasenra in these trials were consistent with the known profile of the medicine.

At the same meeting late last week the CHMP said that diabetes drug Forxiga (dapagliflozin) could have its label changed to include new cardiovascular outcomes data.

The data from the DECLARE-TIMI 58 trial showed the SGLT2 class drug achieved a statistically significant reduction in the composite endpoint for hospitalisation for heart failure or CV death versus placebo, one of the two primary efficacy endpoints.

There were fewer major adverse CV events observed with Forxiga for the other primary efficacy endpoint, but this did not reach statistical significance.

It’s becoming increasingly common for pharma companies to try and show that drugs used to control blood sugar levels in diabetes patients bring cardiovascular benefits.

Eli Lilly and Boehringer Ingelheim were the first to do this with Jardiance, and other companies with drugs from SGLT2 and GLP-1 classes such as Johnson & Johnson and Novo Nordisk have followed the trend.

AZ’s asthma and diabetes drugs get label boosts in EU

NYC Health + Hospitals Rejects Federal Funding Tied to New ‘Gag Rule’

Mayor Bill de Blasio, Deputy Mayor for Health and Human Services Dr. Herminia Palacio, and President and CEO of NYC Health + Hospitals Dr. Mitchell Katz today announced the City’s public health system will cease participating in the federal Title X program for as long as the “gag rule” is in effect. The rule prevents medical providers from sharing information and counseling about abortion to their patients. In a directive to all NYC Health + Hospitals personnel, Dr. Katz today instructed doctors and nurses to support patients on whatever pathway they choose, including providing referrals to abortion and reproductive health services.

In February 2019, the Trump Administration issued the federal “gag rule,” which bars health care providers who receive federal Title X funding from referring or counseling patients about their abortion options. A federal lawsuit – for which New York City filed an amicus brief – had been blocking the gag rule from taking effect. Last week, the Federal Court of Appeals in the Ninth Circuit vacated this injunction, allowing the gag rule to take effect immediately across the country. This would force doctors and medical providers who receive these federal funds for sexual and reproductive health to withhold information about legal abortions from their patients.

Rather than censor providers, NYC Health + Hospitals will reject $1.3 million in federal funding from the Title X program — which funds a range of family planning and related preventive health services — until the gag rule is lifted. The City will cover the lost Title X funds, and NYC Health + Hospitals will direct doctors and nurses to continue providing referrals to abortion and reproductive health services.

Mayor, NYC Health + Hospitals Reject Federal Funding Tied to New “Gag Rule”

Retrophin (RTRX) PT Raised to $41 at Canaccord

Canaccord Genuity analyst Michelle Gilson raised the price target on Retrophin (NASDAQ: RTRX) to $41.00 (from $37.00) while maintaining a Buy rating after the company announced the FDA has approved THIOLA EC 100mg and 300mg tablets for the treatment of cystinuria.

“While we are encouraged by the step forward in the regulatory process, an update on IP around the new formulation is anticipated 2H19 or later,” Gilson commented. “A positive update on IP would help to lift the overhang on generics development further, though would not prevent competition around the original formulation. We expect comparable pricing to original formulation, which should enable access to switching.”

https://www.streetinsider.com/Analyst+Comments/Retrophin+%28RTRX%29+PT+Raised+to+%2441+at+Canaccord+Genuity/15663433.html