Biopharmaceutical News Week # 2016.49

Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation, jcm@btobioinnovation.com

Editor’s Note

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Zika Virus

Nearly a year ago, Zika came onto the world stage in a big way, quickly spreading to more than 50 countries and causing thousands of microcephaly cases. Soon after, the World Health Organization (WHO) deemed the outbreak an international emergency. Now, however, WHO is backing away from that "emergency" distinction. Researchers have demonstrated the link between Zika and microcephaly, and WHO now says that a “robust longer-term” approach is warranted in fighting the virus. It pulled the international emergency label last week. Several experts are criticizing the move saying it “has provided reason for governments and donors to pull back even more” from an already “lethargic” response.

Mergers, Acquisitions and Joint Ventures

Bayer acquires US Boehringer Ingelheim’s Vetmedica Cydectin bovine and ovine endectocide products as a requirement of its acquisition of Sanofi Merial animal health unit. The financial details of the deal were not disclosed.

Business

Spark Therapeutics (Philadelphia, PA, USA) has entered an exclusive licensing agreement with Selecta Biosciences (Watertown, MA,USA) to get rights to its Synthetic Vaccine platform and exclusive options to four additional genetic targets in a deal worth up to $460 million.“Selecta’s nanoparticle technology, which is undergoing preclinical testing in gene therapy, may prevent formation of neutralizing antibodies, and thus potentially enable redosing up to an optimal therapeutic profile by extending the reach of gene therapy to diseases that require higher doses or more extensive transduction of target cells than may be achieved through one-time dosing,” Spark Therapeutics CEO Jeffrey D. Marrazzo said in a statement.

In spite of a serious set back with solanuzemab (see below) Eli Lilly enters an agreement with AstraZeenca to co-develop MEDI1814, an antibody selective for amyloid 42 currently in phase 1, aimed at treating Alzheimer’s disease in building on a deal existing beween both companies related to BACE inhibitor AZD3293. Under the terms of the agreement, Lilly will pay an upfront fee of $30M to AstraZeneca. Other financial terms are not disclosed.

Sanofi buys $10.2 million of insulin from Mannkind, its former Afrezza commercialization partner, as a previously agreed settlement.

Approval of drugs and vaccines

The European Commission has approved the use of AbbVie's Venclyxto, or venetoclax, as a monotherapy for chronic lymphocytic leukemia (CLL) in adults with or without 17p deletion or TP53 genetic mutation whose condition did not improve after treatment with chemoimmunotherapy and a B-cell receptor inhibitor. Venclyxto works by targeting the B‐cell lymphoma‐2 protein, which regulates cell survival, restoring the body's ability to trigger cancer cell self-destruction (apoptosis). The drug was approved by the US FDA in April.

Drugs at clinical stage

The European Medicine Agency (EMA) has accepted Regeneron Pharmaceuticals and Sanofi’s Marketing Autorisation Application of Dupixent or dupilumab, a fully human monoclonal antibody, binding to interleukin-4 (IL-4) and interleukin-13 (IL-13), two major cytokines, for the treatment of adults with moderate-to-severe atopic dermatitis.

US FDA grants fast track to Theravance’s (South San Francisco, CA, USA) TD-5108, or velusetrag, an oral highly selective agonist with high intrinsic activity at the human 5-hydroxtryptamine 4 (5-HT₄) receptor, as a treatment of idiopathic and diabetic gastrioparesis symptoms.

Voyager Therapeutics (Cambridge, MA, USA) announces positive interim results from phase 1 trial of VY-AADCO1 at six and twelve months of follow up in patients with advanced Parkinson’s disease. In advanced Parkinson’s disease, the putamen is depleted of dopamine and of the enzyme aromatic L-amino acid decarboxylase (AADC) that is responsible for converting levodopa to dopamine.  VY-AADC01 is Voyager’s gene therapy vector that contains the gene that encodes the AADC enzyme. 

Novartis’ ribociclib plus Femara, or letrozole, significantly improves progression-free survival in patients with hormone-receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced/metastatic breast cancer compared to letrozole alone. Ribociclib is an orally available cyclin-dependent kinase (CDK) inhibitor targeting cyclin D1/CDK4 and cyclin D3/CDK6 cell cycle pathway, with antineoplastic activity.

Biogen ‘s adacanumab shows remarkable efficacy data in Alzheimer’s disease in a study involving 196 patients. In­ves­ti­ga­tors re­ported that they saw sig­nif­i­cant de­creases in amy­loid plaque bur­den in the brains of pa­tients tak­ing a titrated 10 mg dose of the drug “dur­ing 12 months of treat­ment in ApoE ε4-pos­i­tive pa­tients with pro­dro­mal or mild AD com­pared with placebo.” And they linked that to a clear and sig­nif­i­cant slow­ing of the dis­ease.

…when Eli Lilly had disappointing results with solanezumab. The key fail­ure point was on ADAS-Cog14, which mea­sures a per­son’s cog­ni­tive func­tions, in­clud­ing mem­ory, at­ten­tion and lan­guage abil­i­ties. In­ves­ti­ga­tors tracked an 11% re­duc­tion in the rate of de­cline, a clear miss with a p-value of .095. The sec­ondary end­points were also not met.

Horizon Pharma’s (Dublin, Ireland) Actimmune failed to meet its primary endpoint in a phase 3 clinical trial aimed at showing efficacy as a potential therapy for Friedreich’s ataxia, a rare inherited disease that causes progressive damage of the nervous system.

Medical Devices and Diagnosis News.

Chinese regulators are charging Medtronic a $17.2 million fine for price-fixing. The fines pertain to Medtronic’s cardiovascular and diabetes devices. The National Development and Reform Commission said that Medtronic quashed competition by requiring its distributors in China to charge minimum prices for its products.  Medtronic also had its partners and distributors place lower limits on resale prices to hospitals. "Competition in China's high-value consumables and implantable medical equipment market is inadequate," said a statement by the Cabinet's planning agency. Enforcing minimum prices rather than allowing market forces to set them “increases the burden on patients and damages the interests of consumers.”

Costs, Pricing and Market Access

US President-elect Donald Trump told Time Magazine in an interview published this week: “I am going to bring down drug prices, I don’t like what has happened with drug prices”. The way he sees it, analysts and investors may have misunderstood his intentions, which are, he says, to follow through with pledges he made on the campaign trail. Trump has shown support in the past for letting Medicare negotiate drug prices, the Medicare stance is a pharma-unfriendly measure that crosses his party lines.

Data released this week on the US price history of 5,000 prescription drugs over five years indicate the period to be the fastest rising source oh healthcare costs in recent year. The drug with the biggest rise in cost per unit in Medicare Part D from 2014 to 2015 was Losartan potassium, a generic version of antihypertensive drug Cozaar, which rose 491% in price to the weighted average cost per unit of $3.22 in 2015 from $1.55 in 2014.
The cost of carbamazepine, a generic version of anticonvulsant drug Epitol, jumped 451% to $0.52.  In third place was lisinopril, the generic of ACE inhibitor Zestril, which rose 405% to an average cost per unit of $7.44. Beta-blocker Atenolol, the generic of Tenormin, soared 383% to $7.78 in 2015. And fifth, anti-diabetic drug metformin HCL, the generic of Glumetza, rose 381% to $39.10 in 2015. According to a preliminary analysis of the data by Modern Healthcare, the average price of all Part D drugs sold in both 2015 and 2011 went up 83.6%. For the most common drugs, however—the ones prescribed to more than 4 million beneficiaries in both 2015 and 2011— prices decreased 23.6%. For the drugs that accounted for the most Part D spending—at least $1 billion in both 2015 and 2011—prices increased 59.1%.  The prices for many inexpensive drugs, went up by more than 1,000%. For example, the average cost of the asthma drug mannitol shot up more than 2,000% over the five-year span, from 3 cents per unit to 74 cents per unit. In the Medicare Part B program, which pays for drugs administered in outpatient settings and physician offices, the fastest risers in cost from 2014 to 2015 are primarily injections. 
Cancer drug mitomycin, grew the fastest at 163% to an average of $58.07 per unit, the CMS data shows. Next, aminophyllin, a bronchodilator, rose 115% to $4.97 in 2015.

Pfizer and Flynn Pharma, its UK distribution partner, have been fined nearly £90 million by the UK Competition and Markets Authority (CMA) for for deliberately unbranding an anti-epilepsy drug to enable excessive price hikes. A £84.2 million fine has been imposed on Pfizer and £5.2 million on distributor Flynn Pharma, after the CMA ruled that each broke competition law by charging unfair prices for phenytoin sodium capsules. Originally Pfizer manufactured and sold phenytoin sodium capsules to UK wholesalers and pharmacies under the brand name Epanutin. But the drug's NHS price rocketed 2,600 percent overnight after it was actively genericised in September 2012, through a sale of UK distribution rights to Flynn. Since September 2012, Pfizer has continued to manufacture phenytoin sodium capsules and has supplied them to Flynn at prices "significantly higher" – between 780 percent and 1,600 percent- than those at which it previously sold Epanutin in the UK. Flynn sells on the drug UK wholesalers and pharmacies charging prices which have been between 2,300 percent and 2,600 percent higher than those they had previously paid, according to the agency.

Miscellaneous

Takeda is investing a €100 million in a dengue manufacturing site in Singen (Germany) The construction will begin “immediately” and is slated to be complete in 2019. Takeda declined to give details on the project but did say that the site in Singen has 850 employees. The announcement comes as the drugmaker begins a massive, 20,000-patient phase 3 study in Asia and Latin America of its dengue vaccine candidate.

Mylan (Pittsburgh, PA, USA) said it would eliminate as much as 10% of its workforce (about 3,500 people). In an SEC filing, Mylan said it's "developing the details" of the cutbacks and will share more information about cost savings and restructuring costs as the moves are finalized.

AstraZeneca will cut about 700 jobs in the US including 120 at its North American headquarters in Wilmington, Delaware

Bioevents

9^th Biotech Showcase Investor Conference on January 9-11, 2017 in San Francisco (USA)

JP Morgan Health Conference on January 9-12, 2017, in San Francisco (USA)

BIO CEO & Investor Conference on February 13-17, 2017, New York City (USA)

BIO Asia on March 14-15, 2017, in Tokyo (Japan)

BIO-Europe Spring on March 20-22, 2017 in Barcelona (Spain)

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