Covid-19 disappoints, so Lilly sets out broader goals

 Lilly confirmed today that infused monoclonal antibodies for Covid-19 are unlikely to live up to high commercial hopes, despite impressive clinical data. The company shaved half a billion dollars off its 2021 sales guidance alongside first-quarter results, on lower than expected sales of bamlanivimab and etesevimab. This opportunity was always going to be short term, of course, and more notable from the company today were updates on projects with much greater longevity. Development of tirzepatide, its next big hope in diabetes, is being scaled up to include Nash and heart failure; the gating trial for submission in diabetes, Surpass-4, will read out mid-year. Lilly’s “triple G” tri-agonist will move into mid-stage development, with executives talking up the project's potential and claiming that efficacy could exceed tirzepatide, making this a key metabolic project to watch. Meanwhile, a trial of “thousands” will be started mid-year with donanemab, testing the amyloid-beta MAb in a preventative setting; enrolment will take around a year, while events should take around three years to accrue. These will be costly endeavours, which perhaps help explain Lilly’s decision to abandon its pursuit of approval of mirikizumab in psoriasis, a very crowded field.

Project	Update
Tirzepatide	Surpass-4 (T2D with increased CV risk) data due mid-year; Surmount-1, first ph3 obesity trial, topline due next year; ph3 trials getting under way in obesity (Surmount-J) and obesity with HFpEF (Summit)
Basal insulin-FC	Once-weekly project in ph2; update due at ADA conference mid-year
GGG tri-agonist	To move into ph2 in type 2 diabetes, Nash and obesity; update at ADA conference mid-year
Donanemab	Alzheimer's prevention trial, Trailblazer-Alz3, to start later this year; no path for filing on Trailblazer-Alz
Verzenio	FDA asked for further overall survival data as part of review in adjuvant breast cancer, based on Monarch-E
Mirikizumab	Psoriasis abandoned, development to focus on Crohn's & ulcerative colitis
CD73 inhibitor	Ph1 cancer asset abandoned
ANGPTL3/8 MAb	Ph1 cardiovascular asset abandoned
Source: Lilly Q1 statement/conference call.  https://www.evaluate.com/vantage/articles/news/snippets/covid-19-disappoints-so-lilly-sets-out-broader-goals

Aldeyra eyes the future

 Aldeyra Therapeutics could soon have the first novel allergic conjunctivitis therapy in decades. Its lead project, reproxalap, has delivered a convincing topline win in Invigorate, the second pivotal study of the asset to hit in the disorder.

Perhaps more importantly for Aldeyra, the result could bode well for the much bigger indication of dry eye disease, where phase 3 data with reproxalap are due in the second half of the year. Sellside consensus puts 2026 allergic conjunctivitis sales at $106m, versus $391m in dry eye disease, according to Evaluate Pharma.

Invigorate, comparing reproxalap versus vehicle, hit its primary endpoint, ocular itching. But all eyes were on its key secondary endpoint, ocular redness, as this is the primary outcome measure of the upcoming Tranquility-1 and 2 pivotal trials in dry eye disease.

Here, Invigorate also showed a benefit. There are some differences between the designs of the Invigorate and the Tranquility trials, but there are similarities, and Aldeyra execs were keen to point to the potential read-across to dry eye disease during a conference call this morning. The company’s stock opened up 17%.

Invigorate

In Invigorate, 95 patients received one dose of either reproxalap or vehicle, then went into an allergen chamber, where they were exposed to ragweed pollen for 3.5 hours. They received a dose of either reproxalap or vehicle again at 90 minutes.

Aldeyra had hoped to show a benefit on itching across most of 11 prespecified timepoints 110-210 minutes after patients had entered the chamber. In fact, reproxalap was superior to vehicle across all 11 timepoints, with a p value below 0.001 at each.

Source: Company presentation

Invigorate also met all secondary endpoints. As well as the aforementioned redness measure, it also hit on ocular tearing and total ocular severity score.

The latest success adds to a win in the pivotal Alleviate allergen challenge study two years ago (Aldeyra seeks to Alleviate worries with conjunctivitis win, March 26, 2019).

With many analysts apparently assuming that approval in allergic conjunctivitis is now a formality, questions today focused on how reproxalap might be positioned if it reaches the market.

Aldeyra believes that it would be used after over-the-counter antihistamine eye drops, but before steroid eye drops, which cannot be used chronically owing to side-effects including glaucoma and cataracts. In contrast, reproxalap’s safety profile in Invigorate looked benign, based on the limited data released so far.

Aldeyra will now need to carry out a six-week safety study before it can file reproxalap in allergic conjunctivitis. Management said the group was prepared to launch alone, but might end up partnering the asset.

Tranquility

The allergic conjunctivitis pipeline is sparse: according to Evaluate Pharma, reproxalap is the only project in active late-stage clinical development. Dry eye disease, meanwhile, is much more crowded (Bausch boosted ahead of eye spin-off, April 14, 2021).

Still, if reproxalap can prevail in the Tranquility trials it has a chance to make a mark here, particularly as incumbent drugs like Abbvie’s Restasis and Novartis’s Xiidra leave much to be desired. And approval in both allergic conjunctivitis and dry eye disease would be an advantage as there is around 50% overlap between the two disorders.

Aldeyra’s dry eye studies are also based on a chamber challenge model, but in this case dry air, rather than an allergen, is used as an irritant.

Perhaps the most important difference, however, is dosing. The Tranquility studies have a two-day regimen in which patients receive either reproxalap or vehicle four times on day one, then on day two they are dosed just before entering the chamber, and again 45 minutes into the chamber.

As patients are being exposed to more drug than in Invigorate, investors have another reason to hope for success in the Tranquility trials. They do not have too long to wait to find out.

https://www.evaluate.com/vantage/articles/news/trial-results/aldeyra-eyes-future

Merck to Allow 5 India Generics Manufacturers to Make Covid-19 Treatment

 Merck & Co. said it has entered into non-exclusive voluntary licensing agreements for molnupiravir with five established Indian generics manufacturers.

Merck's molnupiravir is an investigational oral antiviral agent being studied in a Phase 3 trial for the treatment of non-hospitalized patients with confirmed Covid-19. Merck is developing molnupiravir in collaboration with Ridgeback Biotherapeutics.

Merck has entered into these agreements to speed up availability of molnupiravir in India and in other low- and middle-income countries following approvals or emergency authorization by local regulatory agencies.

The agreements have been signed with Cipla Ltd., Dr. Reddy's Laboratories Ltd., Emcure Pharmaceuticals Ltd., Hetero Labs Ltd. and Sun Pharmaceutical Industries Ltd., five generics manufacturers with World Health Organization pre-qualified manufacturing facilities and experience as major drug suppliers.

Under the agreements, Merck will provide licenses to these manufacturers to supply molnupiravir to India and more than 100 low- and middle-income countries. Merck is also in discussions with the Medicines Patent Pool to explore the potential for additional licenses.

Merck said it would also donate more than $5 million worth of oxygen-production equipment, masks, hand sanitizer and financial aid to support relief efforts in India.

https://www.marketscreener.com/quote/stock/MERCK-CO-INC-13611/news/Merck-to-Allow-5-India-Generics-Manufacturers-to-Make-Covid-19-Treatment-33078572/

Humana To Take Full Control Of Home Health Firm Kindred At Home For $5.7 B

 Humana Inc. said it would purchase the remaining stake in a home health and hospice provider that it doesn't already own.

Humana on Tuesday said it would acquire a 60% stake in Kindred at Home from TPG's private-equity arm and Welsh, Carson, Anderson & Stowe, another private-equity investor, for $5.7 billion.

The health-insurance company currently owns a 40% minority interest in Kindred, which employs about 43,000 people who provide home health, hospice and other services in 40 states. Humana described the company as the largest home health and hospice provider in the U.S.

"This acquisition reflects Humana's continued commitment to investing in home-based clinical solutions that drive improved patient outcomes, increased satisfaction for patients and providers and value for health plan partners," the company said.

Kindred will be folded into Humana's home solutions business, the company said, and rebranded as CenterWell Home Health.

Humana also said it plans to maintain only a minority interest in Kindred's hospice and community care operations. It is exploring a potential public listing, among other options, for those assets.

https://www.marketscreener.com/quote/stock/HUMANA-INC-13000/news/Humana-To-Take-Full-Control-Of-Home-Health-Firm-Kindred-At-Home-For-5-7-Billion-33086338/

Pfizer CEO: Oral drug to stop coronavirus could be ready next year

 Pfizer CEO Albert Bourla says that an oral drug for COVID-19 could be ready next year.

“If all goes well, and we implement the same speed that we are, and if regulators do the same, and they are, I hope that by the end of the year,” Bourla said on CNBC's "Squawk Box."

Speaking on "Squawk Box," Bourla said Pfizer is working on two antivirals, an oral and an injectable. 

The company began an early-stage clinical trial of the oral drug late last month. The drug blocks protease, a critical enzyme that the virus needs to replicate.

“Particular attention is on the oral because it provides several advantages,” Bourla said. “One of them is that you don’t need to go to the hospital to get the treatment, which is the case with all the injectables so far. You could get it at home, and that could be a game-changer.”

He also said the medication could be “way more effective against the multiple variants” of the virus than current options.

Bourla said the company should have more news about it later this summer.

Pfizer has a COVID-19 vaccine, which it co-developed with German drug company BioNTech, that was granted emergency authorization by the FDA in December, one of three vaccines against the disease currently approved for use in the U.S.

Thus far, more than 121 million doses of the vaccine have been administered across the country.

https://thehill.com/policy/healthcare/550501-pfizer-ceo-oral-drug-to-stop-coronavirus-could-be-ready-next-year

Ampio Inhaled COVID-19 Treatment Shows 78% Improvement In All-Cause Mortality

 

• Ampio Pharmaceuticals Inc (NYSE: AMPE) revealed positive results from its AP-014 Phase 1 trial utilizing inhaled Ampion in treating respiratory distress in COVID-19 patients.

• The study met its primary endpoint and showed an even greater improvement in all-cause mortality over patients treated using Standard of Care (SOC) than initially reported.

• Mortality in the SOC group was 24%, while that in the group treated with SOC and Ampion was only 5%,

• Preliminary results reported in March showed a lower all-cause mortality rate of 8% in the Ampion group, compared to 21% in the standard of care alone.

• The average hospital length of stay was four days less for the Ampion group than the patients receiving SOC.

• Separately, the Phase 1 study using Ampion to address the respiratory symptoms experienced by COVID-19 "Long Haulers" is awaiting Investigational Review Board approval and is expected to commence enrollment shortly.

• Ampio also received a positive response from the FDA on its plans for its Phase 3 trial utilizing intra-articular injection of Ampion for treating osteoarthritis of the knee.

• The company will provide updates on its plans for this trial at its upcoming May 5th earnings call.

https://finance.yahoo.com/news/ampio-pharmas-inhaled-covid-19-143939390.html

Medtronic Gets FDA Breakthrough Tag for Emprint™ Ablation Catheter Kit

 Minimally Invasive Option Has Potential to Provide Long-Term Management of Lung Malignancies While Protecting Lung Function

https://finance.yahoo.com/news/medtronic-receives-fda-breakthrough-designation-140000004.html