COVID-19 Boosters: Should You Get One?

New MMR Link Found To Autism

by BEEZY MARSH, Daily Mail

Parents' anxieties about the MMR vaccine were heightened yesterday after fresh evidence pointed to a link with autism and bowel disease.

Children suffering autism and a rare form of inflammatory bowel disorder have been found to have the same strain of measles in their intestines as the one in the controversial triple jab.

Although there is no proof that the measles, mumps and rubella jab has actually caused their autism or bowel disease, some experts say the discovery is 'significant'.

Campaign groups and researchers renewed their calls for single jabs to be available on the NHS.

Jackie Fletcher of JABS, which backs parents who believe their children have suffered due to MMR, said: 'This appears to be a key piece of the jigsaw, and there can no longer be any excuse for ministers and doctors to bury their heads in the sand.

'We need further research, but in the meantime the single jab should be made available to all who want it for their children.'

The research builds on earlier work by molecular pathologist Professor John O'Leary, of Trinity College, Dublin, which identified the presence of measles in the guts of children with developmental disorder without identifying the particular strain of the disease.

But the latest research led by Professor O'Leary pins the measles lodged in their guts down to MMR vaccination. Fragments of the MMR measles virus were found in 12 autistic children.

The new findings are due to be presented at the Pathological Society of Great Britain and Ireland next month.

Dr Andrew Wakefield, the specialist who first raised concerns about MMR in 1998, said yesterday: 'The Government says there is no evidence of bowel disease in these children and they are normal.

'Now it has been found that they have the vaccine strain of measles in their gut. That is significant. The Government are running out of places to go on this.

'There can be no justification for not making the single measles jab available.'

Dr Wakefield, who was effectively forced out of his job at the Royal Free Hospital in London, revealed he is to carry out studies on more than 30,000 children who have been given the single measles vaccine-Working with the Direct Health clinic in London, he aims to examine rates of autism and bowel disorder in the large group of children who have never had MMR and compare them with rates among those who have had the triple jab.

The work will be carried out in America, where Dr Wakefield is now based.

Last night, the Department of Health insisted MMR was safe - a view backed by the

British Medical Association, the Royal College of Nursing, the Royal Colleges of Paediatricians and GPs, and the Community Practitioners and Health Visitors' Association.

A spokesman added: 'There is no proven link between MMR, autism and bowel disease and as for its safety, we would point to a BMJ research article last week which looked at more than 2,000 studies and found no evidence of any link.'

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What Is The Modigliani-Miller (M&M) Theorem, And How Is It Used?

What Is the Modigliani-Miller Theorem (M&M)? The Modigliani-Miller theorem (M&M) states that the market value of a company is correctly calculated as the present value of its future earnings and its underlying assets, and is independent of its capital structure. At its most basic level, the theorem argues that, with certain assumptions in place, it is irrelevant whether a company finances its growth by borrowing, by issuing stock shares, or by reinvesting its profits. Developed in the 1950s, the theory has had a significant impact on corporate finance. Understanding the Modigliani-Miller Theorem Companies have only three ways to raise money to finance their operations and fuel their growth and expansion. They can borrow money by issuing bonds or obtaining loans; they can re-invest their profits in their operations, or they can issue new stock shares to investors. Investopedia / Candra Huff The Modigliani-Miller theorem argues that the option or combination of options that a company chooses has no effect on its real market value. Merton Miller, one of the two originators of the theorem, explains the concept behind the theory with an analogy in his book, "Financial Innovations and Market Volatility": "Think of the firm as a gigantic tub of whole milk. The farmer can sell the whole milk as is. Or he can separate out the cream and sell it at a considerably higher price than the whole milk would bring. (That's the analog of a firm selling low-yield and hence high-priced debt securities.) But, of course, what the farmer would have left would be skim milk with low butterfat content and that would sell for much less than whole milk. That corresponds to the levered equity. The M and M proposition says that if there were no costs of separation (and, of course, no government dairy-support programs), the cream plus the skim milk would bring the same price as the whole milk." History of the M&M Theory Merton Miller and Franco Modigliani conceptualized and developed this theorem, and published it in an article, "The Cost of Capital, Corporation Finance and the Theory of Investment," which appeared in the American Economic Review in the late 1950s. Key Takeaways The Modigliani-Miller theorem states that a company's capital structure is not a factor in its value. Market value is determined by the present value of future earnings, the theorem states. The theorem has been highly influential since it was introduced in the 1950s. At the time, both Modigliani and Miller were professors at the Graduate School of Industrial Administration at Carnegie Mellon University. Both were required to teach corporate finance to business students but, unhappily, neither had any experience in corporate finance. After reading the course materials that they were to use, the two professors found the information inconsistent and the concepts flawed. So, they worked together to correct them. Later Additions The result was the groundbreaking article published in the economic journal. The information was eventually compiled and organized to become the M&M theorem. Early on, the two economists realized that their initial theorem left out a number of relevant factors. It left out such matters as taxes and financing costs, effectively arguing its point in the vacuum of a "perfectly efficient market." Later versions of their theorem addressed these issues, including "Corporate Income Taxes and the Cost of Capital: A Correction," published in the 1960s.

Mirum's Volixibat Achieves Positive Interim Analyses In VANTAGE PBC And VISTAS PSC Studies

- VANTAGE PBC interim analysis shows 3.8 point reduction from baseline and 2.3 point placebo-adjusted (p=0.0026) reduction in primary endpoint of pruritus

- VISTAS PSC interim analysis exceeds efficacy threshold for study continuation

- Mirum to host conference call to discuss analyses, today, June 17 at 8:30 a.M. ET/5:30 a.M. PT

FOSTER CITY, Calif., June 17, 2024--(BUSINESS WIRE)--Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced interim results from two Phase 2b studies evaluating volixibat, an oral ileal bile acid transporter (IBAT) inhibitor in patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).

Interim results from the VANTAGE study evaluating volixibat in patients with PBC demonstrated a statistically significant (-3.82, p<0.0001) improvement in pruritus for volixibat and a placebo-adjusted difference of -2.32 points in the primary endpoint, p=0.0026, as measured by the Adult ItchRO scale. 75% of patients on volixibat achieved a greater than 50% reduction in serum bile acids. In addition, there was a significant improvement in fatigue at week 16 with volixibat compared to placebo.

No new safety signals were observed, and adverse events were similar between the 20 mg and 80 mg treatment groups. The most common adverse event was diarrhea (77%) with all cases mild to moderate, and mostly transient; one case resulted in discontinuation. Four patients experienced serious adverse events, including one in the placebo arm. There were no clinically meaningful changes in liver biomarkers.

Adult ItchRO Change from Baseline

Mean change in Adult ItchRO score*

20 mg

(n=10)

80 mg

(n=10)

20+80 mg

(n=20)

PBO

(n=10)

LSMean (SE)

P-value

-3.84 (0.609)

<0.0001

-3.79 (0.564)

<0.0001

-3.82 (0.414)

<0.0001

-1.50 (0.585)

0.0149

Difference between VLX and PBO

P-value

-2.34

0.0090

-2.29

0.0075

-2.32

0.0026

*Adult ItchRO is a 0-10 numerical rating scale; MMRM weekly averaged worst daily itch score, assessed over weeks 17-28 of the treatment period.

Based on these results, the VANTAGE PBC trial will continue with a volixibat dose of 20 mg twice daily.

Story continues

Concurrently, the interim analysis for the VISTAS PSC study was conducted and the independent data review committee recommended that the study continue with the selected volixibat dose of 20 mg twice daily, with no changes to the study. The criteria for continuation included safety as well as a predefined threshold for efficacy. The sponsor and investigators are blinded to the interim results and analysis.

"The interim data from the VANTAGE study provide outstanding results in relation to what has been shown for treatment of pruritus in PBC," said Joanne Quan, MD, chief medical officer at Mirum. "With both VISTAS and VANTAGE advancing to enroll their confirmatory portions, we are excited about volixibat as a potential future option to help patients overcome one of the most prevalent and burdensome symptoms of these rare liver diseases."

"The results of the interim analyses are very impressive as they confirm the potential of volixibat in targeting bile acids in PBC and PSC," said Kris Kowdley, MD, Washington State University and an investigator for VANTAGE and VISTAS. "I look forward to seeing the final data with the goal of having additional therapies available to address the burden of disease in adult cholestasis."

"The symptomatic burden in PBC is significant and often an underappreciated aspect of this disease. Both itch and fatigue are devastating hallmarks of PBC that can significantly decrease quality of life," said Carol Roberts, president of the PBCers Organization. "It is incredibly encouraging for PBC patients to see such promising results with volixibat."

Conference Call to Discuss Interim Analysis

Mirum will be hosting a conference call to discuss the interim analyses from VISTAS and VANTAGE today, Monday, June 17 at 8:30 a.M. ET/5:30 a.M. PT. Join the call by dialing (404) 975-4839 (local/int'l) or (833) 470-1428 (toll-free) and using the access code: 205511. You may also access the webcast through Mirum's Investor Relations website.

About Volixibat

Volixibat is an oral, minimally absorbed agent designed to selectively inhibit the ileal bile acid transporter (IBAT). Volixibat may offer a novel approach in the treatment of adult cholestatic diseases by blocking the recycling of bile acids, through inhibition of IBAT, thereby reducing bile acids systemically and in the liver. Phase 1 and Phase 2 studies of volixibat demonstrated on-target fecal bile acid excretion, a pharmacodynamic marker of ASBT inhibition, in addition to decreases in LDL cholesterol and increases in 7αC4 which are markers of bile acid synthesis. Volixibat has been evaluated in more than 400 individuals across multiple clinical trials. The most common adverse events reported were mild to moderate gastrointestinal events observed in the volixibat groups. Volixibat is currently being evaluated in Phase 2b studies for primary sclerosing cholangitis (VISTAS study), and primary biliary cholangitis (VANTAGE study).

About Mirum Pharmaceuticals, Inc.

Mirum Pharmaceuticals, Inc. Is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution, CHOLBAM® (cholic acid) capsules, and CHENODAL® (chenodiol) tablets.

LIVMARLI, an IBAT inhibitor, is approved for the treatment of two rare liver diseases affecting children and adults. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in other regions globally. It is also approved in the U.S. In cholestatic pruritus in PFIC patients five years of age and older and in Europe the Committee for Medicinal Products for Human Use (CHMP) has adopted positive opinion of LIVMARLI to treat patients with PFIC three months and older. A decision by the European Commission is expected in the third quarter 2024. CHOLBAM is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme deficiencies and adjunctive treatment of peroxisomal disorders in patients who show signs or symptoms or liver disease. CHENODAL has received medical necessity recognition by the FDA to treat patients with cerebrotendinous xanthomatosis (CTX).

Mirum's late-stage pipeline includes two investigational treatments for debilitating liver diseases. Volixibat, an IBAT inhibitor, is being evaluated in two potentially registrational studies including the Phase 2b VISTAS study for primary sclerosing cholangitis and Phase 2b VANTAGE study for primary biliary cholangitis. Lastly, CHENODAL has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023.

To learn more about Mirum, visit mirumpharma.Com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter (X).

LIVMARLI® (maralixibat) Oral SolutionIMPORTANT SAFETY INFORMATION

Limitation of Use: LIVMARLI is not for use in PFIC type 2 patients who have a severe defect in the bile salt export pump (BSEP) protein.

LIVMARLI can cause side effects, including:

Liver injury. Changes in certain liver tests are common in patients with Alagille syndrome and PFIC but can worsen during treatment. These changes may be a sign of liver injury. In PFIC, this can be serious or may lead to liver transplant or death. Your healthcare provider should do blood tests and physical exams before starting and during treatment to check your liver function. Tell your healthcare provider right away if you get any signs or symptoms of liver problems, including nausea or vomiting, skin or the white part of the eye turns yellow, dark or brown urine, pain on the right side of the stomach (abdomen), bloating in your stomach area, loss of appetite or bleeding or bruising more easily than normal.

Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea and stomach pain. Your healthcare provider may advise you to monitor for new or worsening stomach problems including stomach pain, diarrhea, blood in your stool or vomiting. Tell your healthcare provider right away if you have any of these symptoms more often or more severely than normal for you.

A condition called Fat Soluble Vitamin (FSV) Deficiency caused by low levels of certain vitamins (vitamin A, D, E, and K) stored in body fat is common in patients with Alagille syndrome and PFIC but may worsen during treatment. Your healthcare provider should do blood tests before starting and during treatment and may monitor for bone fractures and bleeding which have been reported as common side effects.

US Prescribing InformationEU SmPC

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Such forward-looking statements include those regarding the clinical potential and regulatory process for volixibat, the ability for volixibat to impact bile acids or pruritus in patients with PSC or PBC, and the effectiveness of volixibat in a real-world population, if ever approved by the FDA. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "will," "could," "would," "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Mirum's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Mirum's business in general, the impact of the COVID-19 pandemic, and the other risks described in Mirum's filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. Mirum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. A further description of risks and uncertainties can be found in Mirum's Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors," as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.Sec.Gov.

View source version on businesswire.Com: https://www.Businesswire.Com/news/home/20240617178174/en/

Contacts

Media Contact:Erin Murphymedia@mirumpharma.Com

Investor Contact:Andrew McKibbenir@mirumpharma.Com

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